Daily Papers

Advancements in DNA sequencing technologies have significantly improved our ability to decode genomic sequences. However, the prediction and interpretation of these sequences remain challenging due to the intricate nature of genetic material. Large language models (LLMs) have introduced new opportunities for biological sequence analysis. Recent developments in genomic language models have underscored the potential of LLMs in deciphering DNA sequences. Nonetheless, existing models often face limitations in robustness and application scope, primarily due to constraints in model structure and training data scale. To address these limitations, we present GENERator, a generative genomic foundation model featuring a context length of 98k base pairs (bp) and 1.2B parameters. Trained on an expansive dataset comprising 386B bp of eukaryotic DNA, the GENERator demonstrates state-of-the-art performance across both established and newly proposed benchmarks. The model adheres to the central dogma of molecular biology, accurately generating protein-coding sequences that translate into proteins structurally analogous to known families. It also shows significant promise in sequence optimization, particularly through the prompt-responsive generation of promoter sequences with specific activity profiles. These capabilities position the GENERator as a pivotal tool for genomic research and biotechnological advancement, enhancing our ability to interpret and predict complex biological systems and enabling precise genomic interventions.

Advancements in genomic research such as high-throughput sequencing techniques have driven modern genomic studies into "big data" disciplines. This data explosion is constantly challenging conventional methods used in genomics. In parallel with the urgent demand for robust algorithms, deep learning has succeeded in a variety of fields such as vision, speech, and text processing. Yet genomics entails unique challenges to deep learning since we are expecting from deep learning a superhuman intelligence that explores beyond our knowledge to interpret the genome. A powerful deep learning model should rely on insightful utilization of task-specific knowledge. In this paper, we briefly discuss the strengths of different deep learning models from a genomic perspective so as to fit each particular task with a proper deep architecture, and remark on practical considerations of developing modern deep learning architectures for genomics. We also provide a concise review of deep learning applications in various aspects of genomic research, as well as pointing out potential opportunities and obstacles for future genomics applications.

Recent studies in DNA sequence classification have leveraged sophisticated machine learning techniques, achieving notable accuracy in categorizing complex genomic data. Among these, methods such as k-mer counting have proven effective in distinguishing sequences from varied species like chimpanzees, dogs, and humans, becoming a staple in contemporary genomic research. However, these approaches often demand extensive computational resources, posing a challenge in terms of scalability and efficiency. Addressing this issue, our study introduces a novel adaptation of Jiang et al.'s compressor-based, parameter-free classification method, specifically tailored for DNA sequence analysis. This innovative approach utilizes a variety of compression algorithms, such as Gzip, Brotli, and LZMA, to efficiently process and classify genomic sequences. Not only does this method align with the current state-of-the-art in terms of accuracy, but it also offers a more resource-efficient alternative to traditional machine learning methods. Our comprehensive evaluation demonstrates the proposed method's effectiveness in accurately classifying DNA sequences from multiple species. We present a detailed analysis of the performance of each algorithm used, highlighting the strengths and limitations of our approach in various genomic contexts. Furthermore, we discuss the broader implications of our findings for bioinformatics, particularly in genomic data processing and analysis. The results of our study pave the way for more efficient and scalable DNA sequence classification methods, offering significant potential for advancements in genomic research and applications.

Genomic (DNA) sequences encode an enormous amount of information for gene regulation and protein synthesis. Similar to natural language models, researchers have proposed foundation models in genomics to learn generalizable features from unlabeled genome data that can then be fine-tuned for downstream tasks such as identifying regulatory elements. Due to the quadratic scaling of attention, previous Transformer-based genomic models have used 512 to 4k tokens as context (<0.001% of the human genome), significantly limiting the modeling of long-range interactions in DNA. In addition, these methods rely on tokenizers to aggregate meaningful DNA units, losing single nucleotide resolution where subtle genetic variations can completely alter protein function via single nucleotide polymorphisms (SNPs). Recently, Hyena, a large language model based on implicit convolutions was shown to match attention in quality while allowing longer context lengths and lower time complexity. Leveraging Hyenas new long-range capabilities, we present HyenaDNA, a genomic foundation model pretrained on the human reference genome with context lengths of up to 1 million tokens at the single nucleotide-level, an up to 500x increase over previous dense attention-based models. HyenaDNA scales sub-quadratically in sequence length (training up to 160x faster than Transformer), uses single nucleotide tokens, and has full global context at each layer. We explore what longer context enables - including the first use of in-context learning in genomics for simple adaptation to novel tasks without updating pretrained model weights. On fine-tuned benchmarks from the Nucleotide Transformer, HyenaDNA reaches state-of-the-art (SotA) on 12 of 17 datasets using a model with orders of magnitude less parameters and pretraining data. On the GenomicBenchmarks, HyenaDNA surpasses SotA on all 8 datasets on average by +9 accuracy points.

Keeping track of scientific challenges, advances and emerging directions is a fundamental part of research. However, researchers face a flood of papers that hinders discovery of important knowledge. In biomedicine, this directly impacts human lives. To address this problem, we present a novel task of extraction and search of scientific challenges and directions, to facilitate rapid knowledge discovery. We construct and release an expert-annotated corpus of texts sampled from full-length papers, labeled with novel semantic categories that generalize across many types of challenges and directions. We focus on a large corpus of interdisciplinary work relating to the COVID-19 pandemic, ranging from biomedicine to areas such as AI and economics. We apply a model trained on our data to identify challenges and directions across the corpus and build a dedicated search engine. In experiments with 19 researchers and clinicians using our system, we outperform a popular scientific search engine in assisting knowledge discovery. Finally, we show that models trained on our resource generalize to the wider biomedical domain and to AI papers, highlighting its broad utility. We make our data, model and search engine publicly available. https://challenges.apps.allenai.org/

Large language models (LLMs) have had a transformative impact on a variety of scientific tasks across disciplines such as biology, chemistry, medicine, and physics. However, ensuring the safety alignment of these models in scientific research remains an underexplored area, with existing benchmarks primarily focus on textual content and overlooking key scientific representations such as molecular, protein, and genomic languages. Moreover, the safety mechanisms of LLMs in scientific tasks are insufficiently studied. To address these limitations, we introduce SciSafeEval, a comprehensive benchmark designed to evaluate the safety alignment of LLMs across a range of scientific tasks. SciSafeEval spans multiple scientific languages - including textual, molecular, protein, and genomic - and covers a wide range of scientific domains. We evaluate LLMs in zero-shot, few-shot and chain-of-thought settings, and introduce a 'jailbreak' enhancement feature that challenges LLMs equipped with safety guardrails, rigorously testing their defenses against malicious intention. Our benchmark surpasses existing safety datasets in both scale and scope, providing a robust platform for assessing the safety and performance of LLMs in scientific contexts. This work aims to facilitate the responsible development and deployment of LLMs, promoting alignment with safety and ethical standards in scientific research.

In recent years, large language models (LLMs) have achieved state-of-the-art results in various biological sequence analysis tasks, such as sequence classification, structure prediction, and function prediction. Similar to advancements in AI for other scientific fields, deeper research into biological LLMs has begun to focus on using these models to rediscover important existing biological laws or uncover entirely new patterns in biological sequences.This study leverages GPT-like LLMs to utilize language transfer capabilities to rediscover the genetic code rules of the central dogma. In our experimental design, we transformed the central dogma into a binary classification problem of aligning DNA sequences with protein sequences, where positive examples are matching DNA and protein sequences, and negative examples are non-matching pairs.We first trained a GPT-2 model from scratch using a dataset comprising protein sequences, DNA sequences, and sequences from languages such as English and Chinese. Subsequently, we fine-tuned the model using the English similarity judgment dataset from PAWS-X. When tested on a dataset for DNA and protein sequence alignment judgment, the fine-tuned model achieved a classification accuracy of 76%. The study also analyzed factors contributing to this zero-shot capability, including model training stability and types of training data.This research demonstrates that LLMs can, through the transfer of natural language capabilities and solely relying on the analysis of sequences themselves, rediscover the central dogma without prior knowledge of it. This study opens a new door for AI-driven biological research.

The success of the GPT series proves that GPT can extract general information from sequences, thereby benefiting all downstream tasks. This motivates us to use pre-trained models to explore the hidden information in DNA sequences. However, data and task requirements in DNA sequence analysis are complexity and diversity as DNA relevant data includes different types of information, such as sequences, expression levels, etc, while there is currently no model specifically designed for these characteristics. Hereby, we present DNAGPT, a generalized foundation model pre-trained on over 10 billion base pairs from 9 species which can be fine-tuned for any DNA sequence analysis task. Our model can simultaneously process or output DNA sequences and numbers. In addition, our unique token design allows users to design prompts according to their own task requirements, making it applicable to any type of task. We have evaluated our model on classification, regression, and generation tasks. We demonstrate that DNAGPT benefits from pre-training, and therefore can bring performance gains to any downstream task. Our model is not only a new attempt in the field of genomes analysis, but also provides a new direction for the application of foundation models in biology.

While large language models (LLMs) have been successfully applied to various tasks, they still face challenges with hallucinations. Augmenting LLMs with domain-specific tools such as database utilities can facilitate easier and more precise access to specialized knowledge. In this paper, we present GeneGPT, a novel method for teaching LLMs to use the Web APIs of the National Center for Biotechnology Information (NCBI) for answering genomics questions. Specifically, we prompt Codex to solve the GeneTuring tests with NCBI Web APIs by in-context learning and an augmented decoding algorithm that can detect and execute API calls. Experimental results show that GeneGPT achieves state-of-the-art performance on eight tasks in the GeneTuring benchmark with an average score of 0.83, largely surpassing retrieval-augmented LLMs such as the new Bing (0.44), biomedical LLMs such as BioMedLM (0.08) and BioGPT (0.04), as well as GPT-3 (0.16) and ChatGPT (0.12). Our further analyses suggest that: (1) API demonstrations have good cross-task generalizability and are more useful than documentations for in-context learning; (2) GeneGPT can generalize to longer chains of API calls and answer multi-hop questions in GeneHop, a novel dataset introduced in this work; (3) Different types of errors are enriched in different tasks, providing valuable insights for future improvements.

In this white paper we introduce Helix, an AI based solution for missense pathogenicity prediction. With recent advances in the sequencing of human genomes, massive amounts of genetic data have become available. This has shifted the burden of labor for genetic diagnostics and research from the gathering of data to its interpretation. Helix presents a state of the art platform for the prediction of pathogenicity in human missense variants. In addition to offering best-in-class predictive performance, Helix offers a platform that allows researchers to analyze and interpret variants in depth that can be accessed at helixlabs.ai.

Genome-wide association study (GWAS) tests single nucleotide polymorphism (SNP) markers across the genome to localize the underlying causal variant of a trait. Because causal variants are seldom observed directly, a surrogate model based on genotyped markers are widely considered. Although many methods estimating the parameters of the surrogate model have been proposed, the connection between the surrogate model and the true causal model is yet investigated. In this work, we establish the connection between the surrogate model and the true causal model. The connection shows that population structure is accounted in GWAS by modelling the variant of interest and not the trait. Such observation explains how environmental confounding can be partially corrected using genetic covariates and why the previously claimed connection between PC correction and linear mixed models is incorrect.

Wheat varieties show a large diversity of traits and phenotypes. Linking them to genetic variability is essential for shorter and more efficient wheat breeding programs. Newly desirable wheat variety traits include disease resistance to reduce pesticide use, adaptation to climate change, resistance to heat and drought stresses, or low gluten content of grains. Wheat breeding experiments are documented by a large body of scientific literature and observational data obtained in-field and under controlled conditions. The cross-referencing of complementary information from the literature and observational data is essential to the study of the genotype-phenotype relationship and to the improvement of wheat selection. The scientific literature on genetic marker-assisted selection describes much information about the genotype-phenotype relationship. However, the variety of expressions used to refer to traits and phenotype values in scientific articles is a hinder to finding information and cross-referencing it. When trained adequately by annotated examples, recent text mining methods perform highly in named entity recognition and linking in the scientific domain. While several corpora contain annotations of human and animal phenotypes, currently, no corpus is available for training and evaluating named entity recognition and entity-linking methods in plant phenotype literature. The Triticum aestivum trait Corpus is a new gold standard for traits and phenotypes of wheat. It consists of 540 PubMed references fully annotated for trait, phenotype, and species named entities using the Wheat Trait and Phenotype Ontology and the species taxonomy of the National Center for Biotechnology Information. A study of the performance of tools trained on the Triticum aestivum trait Corpus shows that the corpus is suitable for the training and evaluation of named entity recognition and linking.

The question-answering system for Life science research, which is characterized by the rapid pace of discovery, evolving insights, and complex interactions among knowledge entities, presents unique challenges in maintaining a comprehensive knowledge warehouse and accurate information retrieval. To address these issues, we introduce BioRAG, a novel Retrieval-Augmented Generation (RAG) with the Large Language Models (LLMs) framework. Our approach starts with parsing, indexing, and segmenting an extensive collection of 22 million scientific papers as the basic knowledge, followed by training a specialized embedding model tailored to this domain. Additionally, we enhance the vector retrieval process by incorporating a domain-specific knowledge hierarchy, which aids in modeling the intricate interrelationships among each query and context. For queries requiring the most current information, BioRAG deconstructs the question and employs an iterative retrieval process incorporated with the search engine for step-by-step reasoning. Rigorous experiments have demonstrated that our model outperforms fine-tuned LLM, LLM with search engines, and other scientific RAG frameworks across multiple life science question-answering tasks.

The challenge of replicating research results has posed a significant impediment to the field of molecular biology. The advent of modern intelligent systems has led to notable progress in various domains. Consequently, we embarked on an investigation of intelligent monitoring systems as a means of tackling the issue of the reproducibility crisis. Specifically, we first curate a comprehensive multimodal dataset, named ProBio, as an initial step towards this objective. This dataset comprises fine-grained hierarchical annotations intended for the purpose of studying activity understanding in BioLab. Next, we devise two challenging benchmarks, transparent solution tracking and multimodal action recognition, to emphasize the unique characteristics and difficulties associated with activity understanding in BioLab settings. Finally, we provide a thorough experimental evaluation of contemporary video understanding models and highlight their limitations in this specialized domain to identify potential avenues for future research. We hope ProBio with associated benchmarks may garner increased focus on modern AI techniques in the realm of molecular biology.

DNA sequence alignment involves assigning short DNA reads to the most probable locations on an extensive reference genome. This process is crucial for various genomic analyses, including variant calling, transcriptomics, and epigenomics. Conventional methods, refined over decades, tackle this challenge in 2 steps: genome indexing followed by efficient search to locate likely positions for given reads. Building on the success of Large Language Models in encoding text into embeddings, where the distance metric captures semantic similarity, recent efforts have explored whether the same Transformer architecture can produce embeddings for DNA sequences. Such models have shown early promise in classifying short DNA sequences, such as detecting coding/non-coding regions, and enhancer, promoter sequences. However, performance at sequence classification tasks does not translate to sequence alignment, where it is necessary to search across the genome to align each read, a significantly longer-range task. We bridge this gap by framing the Sequence Alignment task for Transformer models as an "Embed-Search-Align" task. In this framework, a novel Reference-Free DNA Embedding model generates embeddings of reads and reference fragments, which are projected into a shared vector space where the read-fragment distance is used as a surrogate for alignment. Technical contributions include: (1) Contrastive loss for self-supervised training of DNA sequence representations, facilitating rich reference-free, sequence-level embeddings, and (2) a DNA vector store to enable search across fragments on a global scale. DNA-ESA is 99% accurate when aligning 250-length reads onto a human genome (3gb), rivaling conventional methods such as Bowtie and BWA-Mem. DNA-ESA exceeds the performance of 6 Transformer model baselines such as Nucleotide Transformer, Hyena-DNA, and shows task transfer across chromosomes and species.

The scientific research paradigm is undergoing a profound transformation owing to the development of Artificial Intelligence (AI). Recent works demonstrate that various AI-assisted research methods can largely improve research efficiency by improving data analysis, accelerating computation, and fostering novel idea generation. To further move towards the ultimate goal (i.e., automatic scientific research), in this paper, we propose Dolphin, the first closed-loop open-ended auto-research framework to further build the entire process of human scientific research. Dolphin can generate research ideas, perform experiments, and get feedback from experimental results to generate higher-quality ideas. More specifically, Dolphin first generates novel ideas based on relevant papers which are ranked by the topic and task attributes. Then, the codes are automatically generated and debugged with the exception-traceback-guided local code structure. Finally, Dolphin automatically analyzes the results of each idea and feeds the results back to the next round of idea generation. Experiments are conducted on the benchmark datasets of different topics and results show that Dolphin can generate novel ideas continuously and complete the experiment in a loop. We highlight that Dolphin can automatically propose methods that are comparable to the state-of-the-art in some tasks such as 2D image classification and 3D point classification.

The advancement in generative AI could be boosted with more accessible mathematics. Beyond human-AI chat, large language models (LLMs) are emerging in programming, algorithm discovery, and theorem proving, yet their genomics application is limited. This project introduces Math Agents and mathematical embedding as fresh entries to the "Moore's Law of Mathematics", using a GPT-based workflow to convert equations from literature into LaTeX and Python formats. While many digital equation representations exist, there's a lack of automated large-scale evaluation tools. LLMs are pivotal as linguistic user interfaces, providing natural language access for human-AI chat and formal languages for large-scale AI-assisted computational infrastructure. Given the infinite formal possibility spaces, Math Agents, which interact with math, could potentially shift us from "big data" to "big math". Math, unlike the more flexible natural language, has properties subject to proof, enabling its use beyond traditional applications like high-validation math-certified icons for AI alignment aims. This project aims to use Math Agents and mathematical embeddings to address the ageing issue in information systems biology by applying multiscalar physics mathematics to disease models and genomic data. Generative AI with episodic memory could help analyse causal relations in longitudinal health records, using SIR Precision Health models. Genomic data is suggested for addressing the unsolved Alzheimer's disease problem.

With the advent of large multimodal language models, science is now at a threshold of an AI-based technological transformation. Recently, a plethora of new AI models and tools has been proposed, promising to empower researchers and academics worldwide to conduct their research more effectively and efficiently. This includes all aspects of the research cycle, especially (1) searching for relevant literature; (2) generating research ideas and conducting experimentation; generating (3) text-based and (4) multimodal content (e.g., scientific figures and diagrams); and (5) AI-based automatic peer review. In this survey, we provide an in-depth overview over these exciting recent developments, which promise to fundamentally alter the scientific research process for good. Our survey covers the five aspects outlined above, indicating relevant datasets, methods and results (including evaluation) as well as limitations and scope for future research. Ethical concerns regarding shortcomings of these tools and potential for misuse (fake science, plagiarism, harms to research integrity) take a particularly prominent place in our discussion. We hope that our survey will not only become a reference guide for newcomers to the field but also a catalyst for new AI-based initiatives in the area of "AI4Science".

Scientific discovery relies on scientists generating novel hypotheses that undergo rigorous experimental validation. To augment this process, we introduce an AI co-scientist, a multi-agent system built on Gemini 2.0. The AI co-scientist is intended to help uncover new, original knowledge and to formulate demonstrably novel research hypotheses and proposals, building upon prior evidence and aligned to scientist-provided research objectives and guidance. The system's design incorporates a generate, debate, and evolve approach to hypothesis generation, inspired by the scientific method and accelerated by scaling test-time compute. Key contributions include: (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling; (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute, improving hypothesis quality. While general purpose, we focus development and validation in three biomedical areas: drug repurposing, novel target discovery, and explaining mechanisms of bacterial evolution and anti-microbial resistance. For drug repurposing, the system proposes candidates with promising validation findings, including candidates for acute myeloid leukemia that show tumor inhibition in vitro at clinically applicable concentrations. For novel target discovery, the AI co-scientist proposed new epigenetic targets for liver fibrosis, validated by anti-fibrotic activity and liver cell regeneration in human hepatic organoids. Finally, the AI co-scientist recapitulated unpublished experimental results via a parallel in silico discovery of a novel gene transfer mechanism in bacterial evolution. These results, detailed in separate, co-timed reports, demonstrate the potential to augment biomedical and scientific discovery and usher an era of AI empowered scientists.

Medical research generates a large number of publications with the PubMed database already containing >35 million research articles. Integration of the knowledge scattered across this large body of literature could provide key insights into physiological mechanisms and disease processes leading to novel medical interventions. However, it is a great challenge for researchers to utilize this information in full since the scale and complexity of the data greatly surpasses human processing abilities. This becomes especially problematic in cases of extreme urgency like the COVID-19 pandemic. Automated text mining can help extract and connect information from the large body of medical research articles. The first step in text mining is typically the identification of specific classes of keywords (e.g., all protein or disease names), so called Named Entity Recognition (NER). Here we present an end-to-end pipeline for NER of typical entities found in medical research articles, including diseases, cells, chemicals, genes/proteins, and species. The pipeline can access and process large medical research article collections (PubMed, CORD-19) or raw text and incorporates a series of deep learning models fine-tuned on the HUNER corpora collection. In addition, the pipeline can perform dictionary-based NER related to COVID-19 and other medical topics. Users can also load their own NER models and dictionaries to include additional entities. The output consists of publication-ready ranked lists and graphs of detected entities and files containing the annotated texts. An associated script allows rapid inspection of the results for specific entities of interest. As model use cases, the pipeline was deployed on two collections of autophagy-related abstracts from PubMed and on the CORD19 dataset, a collection of 764 398 research article abstracts related to COVID-19.

In domains ranging from computer vision to natural language processing, machine learning models have been shown to exhibit stark disparities, often performing worse for members of traditionally underserved groups. One factor contributing to these performance gaps is a lack of representation in the data the models are trained on. It is often unclear, however, how to operationalize representativeness in specific applications. Here we formalize the problem of creating equitable training datasets, and propose a statistical framework for addressing this problem. We consider a setting where a model builder must decide how to allocate a fixed data collection budget to gather training data from different subgroups. We then frame dataset creation as a constrained optimization problem, in which one maximizes a function of group-specific performance metrics based on (estimated) group-specific learning rates and costs per sample. This flexible approach incorporates preferences of model-builders and other stakeholders, as well as the statistical properties of the learning task. When data collection decisions are made sequentially, we show that under certain conditions this optimization problem can be efficiently solved even without prior knowledge of the learning rates. To illustrate our approach, we conduct a simulation study of polygenic risk scores on synthetic genomic data -- an application domain that often suffers from non-representative data collection. We find that our adaptive sampling strategy outperforms several common data collection heuristics, including equal and proportional sampling, demonstrating the value of strategic dataset design for building equitable models.

The genome sequence contains the blueprint for governing cellular processes. While the availability of genomes has vastly increased over the last decades, experimental annotation of the various functional, non-coding and regulatory elements encoded in the DNA sequence remains both expensive and challenging. This has sparked interest in unsupervised language modeling of genomic DNA, a paradigm that has seen great success for protein sequence data. Although various DNA language models have been proposed, evaluation tasks often differ between individual works, and might not fully recapitulate the fundamental challenges of genome annotation, including the length, scale and sparsity of the data. In this study, we introduce BEND, a Benchmark for DNA language models, featuring a collection of realistic and biologically meaningful downstream tasks defined on the human genome. We find that embeddings from current DNA LMs can approach performance of expert methods on some tasks, but only capture limited information about long-range features. BEND is available at https://github.com/frederikkemarin/BEND.

The rapid growth of scientific literature imposes significant challenges for researchers endeavoring to stay updated with the latest advancements in their fields and delve into new areas. We introduce OpenResearcher, an innovative platform that leverages Artificial Intelligence (AI) techniques to accelerate the research process by answering diverse questions from researchers. OpenResearcher is built based on Retrieval-Augmented Generation (RAG) to integrate Large Language Models (LLMs) with up-to-date, domain-specific knowledge. Moreover, we develop various tools for OpenResearcher to understand researchers' queries, search from the scientific literature, filter retrieved information, provide accurate and comprehensive answers, and self-refine these answers. OpenResearcher can flexibly use these tools to balance efficiency and effectiveness. As a result, OpenResearcher enables researchers to save time and increase their potential to discover new insights and drive scientific breakthroughs. Demo, video, and code are available at: https://github.com/GAIR-NLP/OpenResearcher.

Gene set knowledge discovery is essential for advancing human functional genomics. Recent studies have shown promising performance by harnessing the power of Large Language Models (LLMs) on this task. Nonetheless, their results are subject to several limitations common in LLMs such as hallucinations. In response, we present GeneAgent, a first-of-its-kind language agent featuring self-verification capability. It autonomously interacts with various biological databases and leverages relevant domain knowledge to improve accuracy and reduce hallucination occurrences. Benchmarking on 1,106 gene sets from different sources, GeneAgent consistently outperforms standard GPT-4 by a significant margin. Moreover, a detailed manual review confirms the effectiveness of the self-verification module in minimizing hallucinations and generating more reliable analytical narratives. To demonstrate its practical utility, we apply GeneAgent to seven novel gene sets derived from mouse B2905 melanoma cell lines, with expert evaluations showing that GeneAgent offers novel insights into gene functions and subsequently expedites knowledge discovery.

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

The sparsity of labelled data is an obstacle to the development of Relation Extraction models and the completion of databases in various biomedical areas. While being of high interest in drug-discovery, the natural-products literature, reporting the identification of potential bioactive compounds from organisms, is a concrete example of such an overlooked topic. To mark the start of this new task, we created the first curated evaluation dataset and extracted literature items from the LOTUS database to build training sets. To this end, we developed a new sampler inspired by diversity metrics in ecology, named Greedy Maximum Entropy sampler, or GME-sampler (https://github.com/idiap/gme-sampler). The strategic optimization of both balance and diversity of the selected items in the evaluation set is important given the resource-intensive nature of manual curation. After quantifying the noise in the training set, in the form of discrepancies between the input abstracts text and the expected output labels, we explored different strategies accordingly. Framing the task as an end-to-end Relation Extraction, we evaluated the performance of standard fine-tuning as a generative task and few-shot learning with open Large Language Models (LLaMA 7B-65B). In addition to their evaluation in few-shot settings, we explore the potential of open Large Language Models (Vicuna-13B) as synthetic data generator and propose a new workflow for this purpose. All evaluated models exhibited substantial improvements when fine-tuned on synthetic abstracts rather than the original noisy data. We provide our best performing (f1-score=59.0) BioGPT-Large model for end-to-end RE of natural-products relationships along with all the generated synthetic data and the evaluation dataset. See more details at https://github.com/idiap/abroad-re.

The BigScience Workshop was a value-driven initiative that spanned one and half years of interdisciplinary research and culminated in the creation of ROOTS, a 1.6TB multilingual dataset that was used to train BLOOM, one of the largest multilingual language models to date. In addition to the technical outcomes and artifacts, the workshop fostered multidisciplinary collaborations around large models, datasets, and their analysis. This in turn led to a wide range of research publications spanning topics from ethics to law, data governance, modeling choices and distributed training. This paper focuses on the collaborative research aspects of BigScience and takes a step back to look at the challenges of large-scale participatory research, with respect to participant diversity and the tasks required to successfully carry out such a project. Our main goal is to share the lessons we learned from this experience, what we could have done better and what we did well. We show how the impact of such a social approach to scientific research goes well beyond the technical artifacts that were the basis of its inception.

Recent research trends in computational biology have increasingly focused on integrating text and bio-entity modeling, especially in the context of molecules and proteins. However, previous efforts like BioT5 faced challenges in generalizing across diverse tasks and lacked a nuanced understanding of molecular structures, particularly in their textual representations (e.g., IUPAC). This paper introduces BioT5+, an extension of the BioT5 framework, tailored to enhance biological research and drug discovery. BioT5+ incorporates several novel features: integration of IUPAC names for molecular understanding, inclusion of extensive bio-text and molecule data from sources like bioRxiv and PubChem, the multi-task instruction tuning for generality across tasks, and a novel numerical tokenization technique for improved processing of numerical data. These enhancements allow BioT5+ to bridge the gap between molecular representations and their textual descriptions, providing a more holistic understanding of biological entities, and largely improving the grounded reasoning of bio-text and bio-sequences. The model is pre-trained and fine-tuned with a large number of experiments, including 3 types of problems (classification, regression, generation), 15 kinds of tasks, and 21 total benchmark datasets, demonstrating the remarkable performance and state-of-the-art results in most cases. BioT5+ stands out for its ability to capture intricate relationships in biological data, thereby contributing significantly to bioinformatics and computational biology. Our code is available at https://github.com/QizhiPei/BioT5.

Interrogating the evolution of biological changes at early stages of life requires longitudinal profiling of molecules, such as DNA methylation, which can be challenging with children. We introduce a probabilistic and longitudinal machine learning framework based on multi-mean Gaussian processes (GPs), accounting for individual and gene correlations across time. This method provides future predictions of DNA methylation status at different individual ages while accounting for uncertainty. Our model is trained on a birth cohort of children with methylation profiled at ages 0-4, and we demonstrated that the status of methylation sites for each child can be accurately predicted at ages 5-7. We show that methylation profiles predicted by multi-mean GPs can be used to estimate other phenotypes, such as epigenetic age, and enable comparison to other health measures of interest. This approach encourages epigenetic studies to move towards longitudinal design for investigating epigenetic changes during development, ageing and disease progression.

Predicting ATP-Protein Binding sites in genes is of great significance in the field of Biology and Medicine. The majority of research in this field has been conducted through time- and resource-intensive 'wet experiments' in laboratories. Over the years, researchers have been investigating computational methods computational methods to accomplish the same goals, utilising the strength of advanced Deep Learning and NLP algorithms. In this paper, we propose to develop methods to classify ATP-Protein binding sites. We conducted various experiments mainly using PSSMs and several word embeddings as features. We used 2D CNNs and LightGBM classifiers as our chief Deep Learning Algorithms. The MP3Vec and BERT models have also been subjected to testing in our study. The outcomes of our experiments demonstrated improvement over the state-of-the-art benchmarks.

Computing in the life sciences has undergone a transformative evolution, from early computational models in the 1950s to the applications of artificial intelligence (AI) and machine learning (ML) seen today. This paper highlights key milestones and technological advancements through the historical development of computing in the life sciences. The discussion includes the inception of computational models for biological processes, the advent of bioinformatics tools, and the integration of AI/ML in modern life sciences research. Attention is given to AI-enabled tools used in the life sciences, such as scientific large language models and bio-AI tools, examining their capabilities, limitations, and impact to biological risk. This paper seeks to clarify and establish essential terminology and concepts to ensure informed decision-making and effective communication across disciplines.

This comprehensive survey explored the evolving landscape of generative Artificial Intelligence (AI), with a specific focus on the transformative impacts of Mixture of Experts (MoE), multimodal learning, and the speculated advancements towards Artificial General Intelligence (AGI). It critically examined the current state and future trajectory of generative Artificial Intelligence (AI), exploring how innovations like Google's Gemini and the anticipated OpenAI Q* project are reshaping research priorities and applications across various domains, including an impact analysis on the generative AI research taxonomy. It assessed the computational challenges, scalability, and real-world implications of these technologies while highlighting their potential in driving significant progress in fields like healthcare, finance, and education. It also addressed the emerging academic challenges posed by the proliferation of both AI-themed and AI-generated preprints, examining their impact on the peer-review process and scholarly communication. The study highlighted the importance of incorporating ethical and human-centric methods in AI development, ensuring alignment with societal norms and welfare, and outlined a strategy for future AI research that focuses on a balanced and conscientious use of MoE, multimodality, and AGI in generative AI.

The approval success rate of drug candidates is very low with the majority of failure due to safety and efficacy. Increasingly available high dimensional information on targets, drug molecules and indications provides an opportunity for ML methods to integrate multiple data modalities and better predict clinically promising drug targets. Notably, drug targets with human genetics evidence are shown to have better odds to succeed. However, a recent tensor factorization-based approach found that additional information on targets and indications might not necessarily improve the predictive accuracy. Here we revisit this approach by integrating different types of human genetics evidence collated from publicly available sources to support each target-indication pair. We use Bayesian tensor factorization to show that models incorporating all available human genetics evidence (rare disease, gene burden, common disease) modestly improves the clinical outcome prediction over models using single line of genetics evidence. We provide additional insight into the relative predictive power of different types of human genetics evidence for predicting the success of clinical outcomes.

Pre-trained language models have attracted increasing attention in the biomedical domain, inspired by their great success in the general natural language domain. Among the two main branches of pre-trained language models in the general language domain, i.e., BERT (and its variants) and GPT (and its variants), the first one has been extensively studied in the biomedical domain, such as BioBERT and PubMedBERT. While they have achieved great success on a variety of discriminative downstream biomedical tasks, the lack of generation ability constrains their application scope. In this paper, we propose BioGPT, a domain-specific generative Transformer language model pre-trained on large scale biomedical literature. We evaluate BioGPT on six biomedical NLP tasks and demonstrate that our model outperforms previous models on most tasks. Especially, we get 44.98%, 38.42% and 40.76% F1 score on BC5CDR, KD-DTI and DDI end-to-end relation extraction tasks respectively, and 78.2% accuracy on PubMedQA, creating a new record. Our larger model BioGPT-Large achieves 81.0% on PubMedQA. Our case study on text generation further demonstrates the advantage of BioGPT on biomedical literature to generate fluent descriptions for biomedical terms. Code is available at https://github.com/microsoft/BioGPT.

As computational work becomes more and more integral to many aspects of scientific research, computational reproducibility has become an issue of increasing importance to computer systems researchers and domain scientists alike. Though computational reproducibility seems more straight forward than replicating physical experiments, the complex and rapidly changing nature of computer environments makes being able to reproduce and extend such work a serious challenge. In this paper, I explore common reasons that code developed for one research project cannot be successfully executed or extended by subsequent researchers. I review current approaches to these issues, including virtual machines and workflow systems, and their limitations. I then examine how the popular emerging technology Docker combines several areas from systems research - such as operating system virtualization, cross-platform portability, modular re-usable elements, versioning, and a `DevOps' philosophy, to address these challenges. I illustrate this with several examples of Docker use with a focus on the R statistical environment.

Unequal access to costly datasets essential for empirical research has long hindered researchers from disadvantaged institutions, limiting their ability to contribute to their fields and advance their careers. Recent breakthroughs in Large Language Models (LLMs) have the potential to democratize data access by automating data collection from unstructured sources. We develop and evaluate a novel methodology using GPT-4o-mini within a Retrieval-Augmented Generation (RAG) framework to collect data from corporate disclosures. Our approach achieves human-level accuracy in collecting CEO pay ratios from approximately 10,000 proxy statements and Critical Audit Matters (CAMs) from more than 12,000 10-K filings, with LLM processing times of 9 and 40 minutes respectively, each at a cost under $10. This stands in stark contrast to the hundreds of hours needed for manual collection or the thousands of dollars required for commercial database subscriptions. To foster a more inclusive research community by empowering researchers with limited resources to explore new avenues of inquiry, we share our methodology and the resulting datasets.

Although DNA foundation models have advanced the understanding of genomes, they still face significant challenges in the limited scale and diversity of genomic data. This limitation starkly contrasts with the success of natural language foundation models, which thrive on substantially larger scales. Furthermore, genome understanding involves numerous downstream genome annotation tasks with inherent data heterogeneity, thereby necessitating more efficient and robust fine-tuning methods tailored for genomics. Here, we present Lingo: Language prefix fIne-tuning for GenOmes. Unlike DNA foundation models, Lingo strategically leverages natural language foundation models' contextual cues, recalibrating their linguistic knowledge to genomic sequences. Lingo further accommodates numerous, heterogeneous downstream fine-tune tasks by an adaptive rank sampling method that prunes and stochastically reintroduces pruned singular vectors within small computational budgets. Adaptive rank sampling outperformed existing fine-tuning methods on all benchmarked 14 genome understanding tasks, while requiring fewer than 2\% of trainable parameters as genomic-specific adapters. Impressively, applying these adapters on natural language foundation models matched or even exceeded the performance of DNA foundation models. Lingo presents a new paradigm of efficient and scalable genome understanding via genomic-specific adapters on language models.

The way in which data are shared can affect their utility and reusability. Here, we demonstrate how data that we had previously shared in bulk can be mobilized further through a knowledge graph that allows for much more granular exploration and interrogation. The original dataset is about the computational reproducibility of GitHub-hosted Jupyter notebooks associated with biomedical publications. It contains rich metadata about the publications, associated GitHub repositories and Jupyter notebooks, and the notebooks' reproducibility. We took this dataset, converted it into semantic triples and loaded these into a triple store to create a knowledge graph, FAIR Jupyter, that we made accessible via a web service. This enables granular data exploration and analysis through queries that can be tailored to specific use cases. Such queries may provide details about any of the variables from the original dataset, highlight relationships between them or combine some of the graph's content with materials from corresponding external resources. We provide a collection of example queries addressing a range of use cases in research and education. We also outline how sets of such queries can be used to profile specific content types, either individually or by class. We conclude by discussing how such a semantically enhanced sharing of complex datasets can both enhance their FAIRness, i.e., their findability, accessibility, interoperability, and reusability, and help identify and communicate best practices, particularly with regards to data quality, standardization, automation and reproducibility.

"An idea is nothing more nor less than a new combination of old elements" (Young, J.W.). The widespread adoption of Large Language Models (LLMs) and publicly available ChatGPT have marked a significant turning point in the integration of Artificial Intelligence (AI) into people's everyday lives. This study explores the capability of LLMs in generating novel research ideas based on information from research papers. We conduct a thorough examination of 4 LLMs in five domains (e.g., Chemistry, Computer, Economics, Medical, and Physics). We found that the future research ideas generated by Claude-2 and GPT-4 are more aligned with the author's perspective than GPT-3.5 and Gemini. We also found that Claude-2 generates more diverse future research ideas than GPT-4, GPT-3.5, and Gemini 1.0. We further performed a human evaluation of the novelty, relevancy, and feasibility of the generated future research ideas. This investigation offers insights into the evolving role of LLMs in idea generation, highlighting both its capability and limitations. Our work contributes to the ongoing efforts in evaluating and utilizing language models for generating future research ideas. We make our datasets and codes publicly available.

The drug development pipeline for a new compound can last 10-20 years and cost over 10 billion. Drug repurposing offers a more time- and cost-effective alternative. Computational approaches based on biomedical knowledge graph representations have recently yielded new drug repurposing hypotheses. In this study, we present a novel, disease-specific hypergraph representation learning technique to derive contextual embeddings of biological pathways of various lengths but that all start at any given drug and all end at the disease of interest. Further, we extend this method to multi-disease hypergraphs. To determine the repurposing potential of each of the 1,522 drugs, we derive drug-specific distributions of cosine similarity values and ultimately consider the median for ranking. Cosine similarity values are computed between (1) all biological pathways starting at the considered drug and ending at the disease of interest and (2) all biological pathways starting at drugs currently prescribed against that disease and ending at the disease of interest. We illustrate our approach with Alzheimer's disease (AD) and two of its risk factors: hypertension (HTN) and type 2 diabetes (T2D). We compare each drug's rank across four hypergraph settings (single- or multi-disease): AD only, AD + HTN, AD + T2D, and AD + HTN + T2D. Notably, our framework led to the identification of two promising drugs whose repurposing potential was significantly higher in hypergraphs combining two diseases: dapagliflozin (antidiabetic; moved up, from top 32% to top 7%, across all considered drugs) and debrisoquine (antihypertensive; moved up, from top 76% to top 23%). Our approach serves as a hypothesis generation tool, to be paired with a validation pipeline relying on laboratory experiments and semi-automated parsing of the biomedical literature.

Recent advancements in specialized large-scale architectures for training image and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT4 have demonstrated exceptional capabilities in processing, translating, and generating human languages. These breakthroughs have also been reflected in protein research, leading to the rapid development of numerous new methods in a short time, with unprecedented performance. Language models, in particular, have seen widespread use in protein research, as they have been utilized to embed proteins, generate novel ones, and predict tertiary structures. In this book chapter, we provide an overview of the use of protein generative models, reviewing 1) language models for the design of novel artificial proteins, 2) works that use non-Transformer architectures, and 3) applications in directed evolution approaches.

Decoding the linguistic intricacies of the genome is a crucial problem in biology, and pre-trained foundational models such as DNABERT and Nucleotide Transformer have made significant strides in this area. Existing works have largely hinged on k-mer, fixed-length permutations of A, T, C, and G, as the token of the genome language due to its simplicity. However, we argue that the computation and sample inefficiencies introduced by k-mer tokenization are primary obstacles in developing large genome foundational models. We provide conceptual and empirical insights into genome tokenization, building on which we propose to replace k-mer tokenization with Byte Pair Encoding (BPE), a statistics-based data compression algorithm that constructs tokens by iteratively merging the most frequent co-occurring genome segment in the corpus. We demonstrate that BPE not only overcomes the limitations of k-mer tokenization but also benefits from the computational efficiency of non-overlapping tokenization. Based on these insights, we introduce DNABERT-2, a refined genome foundation model that adapts an efficient tokenizer and employs multiple strategies to overcome input length constraints, reduce time and memory expenditure, and enhance model capability. Furthermore, we identify the absence of a comprehensive and standardized benchmark for genome understanding as another significant impediment to fair comparative analysis. In response, we propose the Genome Understanding Evaluation (GUE), a comprehensive multi-species genome classification dataset that amalgamates 28 distinct datasets across 7 tasks, with input lengths ranging from 70 to 1000. Through comprehensive experiments on the GUE benchmark, we demonstrate that DNABERT-2 achieves comparable performance to the state-of-the-art model with 21 times fewer parameters and approximately 56 times less GPU time in pre-training.

Motivation The genotype assignment problem consists of predicting, from the genotype of an individual, which of a known set of populations it originated from. The problem arises in a variety of contexts, including wildlife forensics, invasive species detection and biodiversity monitoring. Existing approaches perform well under ideal conditions but are sensitive to a variety of common violations of the assumptions they rely on. Results In this article, we introduce Mycorrhiza, a machine learning approach for the genotype assignment problem. Our algorithm makes use of phylogenetic networks to engineer features that encode the evolutionary relationships among samples. Those features are then used as input to a Random Forests classifier. The classification accuracy was assessed on multiple published empirical SNP, microsatellite or consensus sequence datasets with wide ranges of size, geographical distribution and population structure and on simulated datasets. It compared favorably against widely used assessment tests or mixture analysis methods such as STRUCTURE and Admixture, and against another machine-learning based approach using principal component analysis for dimensionality reduction. Mycorrhiza yields particularly significant gains on datasets with a large average fixation index (FST) or deviation from the Hardy-Weinberg equilibrium. Moreover, the phylogenetic network approach estimates mixture proportions with good accuracy.

We pretrain METAGENE-1, a 7-billion-parameter autoregressive transformer model, which we refer to as a metagenomic foundation model, on a novel corpus of diverse metagenomic DNA and RNA sequences comprising over 1.5 trillion base pairs. This dataset is sourced from a large collection of human wastewater samples, processed and sequenced using deep metagenomic (next-generation) sequencing methods. Unlike genomic models that focus on individual genomes or curated sets of specific species, the aim of METAGENE-1 is to capture the full distribution of genomic information present within this wastewater, to aid in tasks relevant to pandemic monitoring and pathogen detection. We carry out byte-pair encoding (BPE) tokenization on our dataset, tailored for metagenomic sequences, and then pretrain our model. In this paper, we first detail the pretraining dataset, tokenization strategy, and model architecture, highlighting the considerations and design choices that enable the effective modeling of metagenomic data. We then show results of pretraining this model on our metagenomic dataset, providing details about our losses, system metrics, and training stability over the course of pretraining. Finally, we demonstrate the performance of METAGENE-1, which achieves state-of-the-art results on a set of genomic benchmarks and new evaluations focused on human-pathogen detection and genomic sequence embedding, showcasing its potential for public health applications in pandemic monitoring, biosurveillance, and early detection of emerging health threats.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, significantly impacting cost, mortality, and burden worldwide. The advent of high-throughput omics technologies, such as genomics, transcriptomics, proteomics, and epigenomics, has revolutionized the molecular understanding of AD. Conventional AI approaches typically require the completion of all omics data at the outset to achieve optimal AD diagnosis, which are inefficient and may be unnecessary. To reduce the clinical cost and improve the accuracy of AD diagnosis using multi-omics data, we propose a novel staged graph convolutional network with uncertainty quantification (SGUQ). SGUQ begins with mRNA and progressively incorporates DNA methylation and miRNA data only when necessary, reducing overall costs and exposure to harmful tests. Experimental results indicate that 46.23% of the samples can be reliably predicted using only single-modal omics data (mRNA), while an additional 16.04% of the samples can achieve reliable predictions when combining two omics data types (mRNA + DNA methylation). In addition, the proposed staged SGUQ achieved an accuracy of 0.858 on ROSMAP dataset, which outperformed existing methods significantly. The proposed SGUQ can not only be applied to AD diagnosis using multi-omics data but also has the potential for clinical decision-making using multi-viewed data. Our implementation is publicly available at https://github.com/chenzhao2023/multiomicsuncertainty.

Building a general-purpose task model similar to ChatGPT has been an important research direction for gene large language models. Instruction fine-tuning is a key component in building ChatGPT, but existing instructions are primarily based on natural language. Natural language and gene sequences have significant differences in tokenization and encoding. Therefore, constructing a multilingual model that can handle both natural language and gene sequences is crucial for solving this problem.In this paper, we expand the capabilities of the LLaMA large language model to include gene language. This involves expanding the vocabulary using the Byte Pair Encoding (BPE) method, specifically tailored for DNA and protein sequences, and conducting further pre-training on these sequences. We then convert various downstream gene task data into a unified format for instruction fine-tuning and further fine-tune the model on this data.Our study demonstrates that a mixed model of gene and natural language, fine-tuned with instructions, achieves results comparable to the current state-of-the-art (SOTA) in tasks such as gene classification and gene sequence interaction. This provides a promising direction for building a unified large language model for gene tasks.

Predicting gene function from its DNA sequence is a fundamental challenge in biology. Many deep learning models have been proposed to embed DNA sequences and predict their enzymatic function, leveraging information in public databases linking DNA sequences to an enzymatic function label. However, much of the scientific community's knowledge of biological function is not represented in these categorical labels, and is instead captured in unstructured text descriptions of mechanisms, reactions, and enzyme behavior. These descriptions are often captured alongside DNA sequences in biological databases, albeit in an unstructured manner. Deep learning of models predicting enzymatic function are likely to benefit from incorporating this multi-modal data encoding scientific knowledge of biological function. There is, however, no dataset designed for machine learning algorithms to leverage this multi-modal information. Here we propose a novel dataset and benchmark suite that enables the exploration and development of large multi-modal neural network models on gene DNA sequences and natural language descriptions of gene function. We present baseline performance on benchmarks for both unsupervised and supervised tasks that demonstrate the difficulty of this modeling objective, while demonstrating the potential benefit of incorporating multi-modal data types in function prediction compared to DNA sequences alone. Our dataset is at: https://hoarfrost-lab.github.io/BioTalk/.

Large participatory biomedical studies, studies that recruit individuals to join a dataset, are gaining popularity and investment, especially for analysis by modern AI methods. Because they purposively recruit participants, these studies are uniquely able to address a lack of historical representation, an issue that has affected many biomedical datasets. In this work, we define representativeness as the similarity to a target population distribution of a set of attributes and our goal is to mirror the U.S. population across distributions of age, gender, race, and ethnicity. Many participatory studies recruit at several institutions, so we introduce a computational approach to adaptively allocate recruitment resources among sites to improve representativeness. In simulated recruitment of 10,000-participant cohorts from medical centers in the STAR Clinical Research Network, we show that our approach yields a more representative cohort than existing baselines. Thus, we highlight the value of computational modeling in guiding recruitment efforts.

Language models can serve as a valuable tool for software developers to increase productivity. Large generative models can be used for code generation and code completion, while smaller encoder-only models are capable of performing code search tasks using natural language queries.These capabilities are heavily influenced by the quality and diversity of the available training data. Source code datasets used for training usually focus on the most popular languages and testing is mostly conducted on the same distributions, often overlooking low-resource programming languages. Motivated by the NLP generalization taxonomy proposed by Hupkes et.\,al., we propose a new benchmark dataset called GenCodeSearchNet (GeCS) which builds upon existing natural language code search datasets to systemically evaluate the programming language understanding generalization capabilities of language models. As part of the full dataset, we introduce a new, manually curated subset StatCodeSearch that focuses on R, a popular but so far underrepresented programming language that is often used by researchers outside the field of computer science. For evaluation and comparison, we collect several baseline results using fine-tuned BERT-style models and GPT-style large language models in a zero-shot setting.

The World Health Organization added Disease X to their shortlist of blueprint priority diseases to represent a hypothetical, unknown pathogen that could cause a future epidemic. During different virus outbreaks of the past, such as COVID-19, Influenza, Lyme Disease, and Zika virus, researchers from various disciplines utilized Google Trends to mine multimodal components of web behavior to study, investigate, and analyze the global awareness, preparedness, and response associated with these respective virus outbreaks. As the world prepares for Disease X, a dataset on web behavior related to Disease X would be crucial to contribute towards the timely advancement of research in this field. Furthermore, none of the prior works in this field have focused on the development of a dataset to compile relevant web behavior data, which would help to prepare for Disease X. To address these research challenges, this work presents a dataset of web behavior related to Disease X, which emerged from different geographic regions of the world, between February 2018 and August 2023. Specifically, this dataset presents the search interests related to Disease X from 94 geographic regions. The dataset was developed by collecting data using Google Trends. The relevant search interests for all these regions for each month in this time range are available in this dataset. This paper also discusses the compliance of this dataset with the FAIR principles of scientific data management. Finally, an analysis of this dataset is presented to uphold the applicability, relevance, and usefulness of this dataset for the investigation of different research questions in the interrelated fields of Big Data, Data Mining, Healthcare, Epidemiology, and Data Analysis with a specific focus on Disease X.

Keyphrase generation is the task consisting in generating a set of words or phrases that highlight the main topics of a document. There are few datasets for keyphrase generation in the biomedical domain and they do not meet the expectations in terms of size for training generative models. In this paper, we introduce kp-biomed, the first large-scale biomedical keyphrase generation dataset with more than 5M documents collected from PubMed abstracts. We train and release several generative models and conduct a series of experiments showing that using large scale datasets improves significantly the performances for present and absent keyphrase generation. The dataset is available under CC-BY-NC v4.0 license at https://huggingface.co/ datasets/taln-ls2n/kpbiomed.

The exponential surge in online health information, coupled with its increasing use by non-experts, highlights the pressing need for advanced Health Information Retrieval models that consider not only topical relevance but also the factual accuracy of the retrieved information, given the potential risks associated with health misinformation. To this aim, this paper introduces a solution driven by Retrieval-Augmented Generation (RAG), which leverages the capabilities of generative Large Language Models (LLMs) to enhance the retrieval of health-related documents grounded in scientific evidence. In particular, we propose a three-stage model: in the first stage, the user's query is employed to retrieve topically relevant passages with associated references from a knowledge base constituted by scientific literature. In the second stage, these passages, alongside the initial query, are processed by LLMs to generate a contextually relevant rich text (GenText). In the last stage, the documents to be retrieved are evaluated and ranked both from the point of view of topical relevance and factual accuracy by means of their comparison with GenText, either through stance detection or semantic similarity. In addition to calculating factual accuracy, GenText can offer a layer of explainability for it, aiding users in understanding the reasoning behind the retrieval. Experimental evaluation of our model on benchmark datasets and against baseline models demonstrates its effectiveness in enhancing the retrieval of both topically relevant and factually accurate health information, thus presenting a significant step forward in the health misinformation mitigation problem.

Introduction: The scientific publishing landscape is expanding rapidly, creating challenges for researchers to stay up-to-date with the evolution of the literature. Natural Language Processing (NLP) has emerged as a potent approach to automating knowledge extraction from this vast amount of publications and preprints. Tasks such as Named-Entity Recognition (NER) and Named-Entity Linking (NEL), in conjunction with context-dependent semantic interpretation, offer promising and complementary approaches to extracting structured information and revealing key concepts. Results: We present the SourceData-NLP dataset produced through the routine curation of papers during the publication process. A unique feature of this dataset is its emphasis on the annotation of bioentities in figure legends. We annotate eight classes of biomedical entities (small molecules, gene products, subcellular components, cell lines, cell types, tissues, organisms, and diseases), their role in the experimental design, and the nature of the experimental method as an additional class. SourceData-NLP contains more than 620,000 annotated biomedical entities, curated from 18,689 figures in 3,223 papers in molecular and cell biology. We illustrate the dataset's usefulness by assessing BioLinkBERT and PubmedBERT, two transformers-based models, fine-tuned on the SourceData-NLP dataset for NER. We also introduce a novel context-dependent semantic task that infers whether an entity is the target of a controlled intervention or the object of measurement. Conclusions: SourceData-NLP's scale highlights the value of integrating curation into publishing. Models trained with SourceData-NLP will furthermore enable the development of tools able to extract causal hypotheses from the literature and assemble them into knowledge graphs.

This paper introduces a novel framework for DNA sequence generation, comprising two key components: DiscDiff, a Latent Diffusion Model (LDM) tailored for generating discrete DNA sequences, and Absorb-Escape, a post-training algorithm designed to refine these sequences. Absorb-Escape enhances the realism of the generated sequences by correcting `round errors' inherent in the conversion process between latent and input spaces. Our approach not only sets new standards in DNA sequence generation but also demonstrates superior performance over existing diffusion models, in generating both short and long DNA sequences. Additionally, we introduce EPD-GenDNA, the first comprehensive, multi-species dataset for DNA generation, encompassing 160,000 unique sequences from 15 species. We hope this study will advance the generative modelling of DNA, with potential implications for gene therapy and protein production.

Synthetic data generation has the potential to impact applications and domains with scarce data. However, before such data is used for sensitive tasks such as mental health, we need an understanding of how different demographics are represented in it. In our paper, we analyze the potential of producing synthetic data using GPT-3 by exploring the various stressors it attributes to different race and gender combinations, to provide insight for future researchers looking into using LLMs for data generation. Using GPT-3, we develop HEADROOM, a synthetic dataset of 3,120 posts about depression-triggering stressors, by controlling for race, gender, and time frame (before and after COVID-19). Using this dataset, we conduct semantic and lexical analyses to (1) identify the predominant stressors for each demographic group; and (2) compare our synthetic data to a human-generated dataset. We present the procedures to generate queries to develop depression data using GPT-3, and conduct analyzes to uncover the types of stressors it assigns to demographic groups, which could be used to test the limitations of LLMs for synthetic data generation for depression data. Our findings show that synthetic data mimics some of the human-generated data distribution for the predominant depression stressors across diverse demographics.

The use of Project Gutenberg (PG) as a text corpus has been extremely popular in statistical analysis of language for more than 25 years. However, in contrast to other major linguistic datasets of similar importance, no consensual full version of PG exists to date. In fact, most PG studies so far either consider only a small number of manually selected books, leading to potential biased subsets, or employ vastly different pre-processing strategies (often specified in insufficient details), raising concerns regarding the reproducibility of published results. In order to address these shortcomings, here we present the Standardized Project Gutenberg Corpus (SPGC), an open science approach to a curated version of the complete PG data containing more than 50,000 books and more than 3 times 10^9 word-tokens. Using different sources of annotated metadata, we not only provide a broad characterization of the content of PG, but also show different examples highlighting the potential of SPGC for investigating language variability across time, subjects, and authors. We publish our methodology in detail, the code to download and process the data, as well as the obtained corpus itself on 3 different levels of granularity (raw text, timeseries of word tokens, and counts of words). In this way, we provide a reproducible, pre-processed, full-size version of Project Gutenberg as a new scientific resource for corpus linguistics, natural language processing, and information retrieval.

Background: Cancer remains one of the leading causes of morbidity and mortality worldwide. Comprehensive datasets that combine histopathological images with genetic and survival data across various tumour sites are essential for advancing computational pathology and personalised medicine. Results: We present SurGen, a dataset comprising 1,020 H&E-stained whole slide images (WSIs) from 843 colorectal cancer cases. The dataset includes detailed annotations for key genetic mutations (KRAS, NRAS, BRAF) and mismatch repair status, as well as survival data for 426 cases. To demonstrate SurGen's practical utility, we conducted a proof-of-concept machine learning experiment predicting mismatch repair status from the WSIs, achieving a test AUROC of 0.8316. These preliminary results underscore the dataset's potential to facilitate research in biomarker discovery, prognostic modelling, and advanced machine learning applications in colorectal cancer. Conclusions: SurGen offers a valuable resource for the scientific community, enabling studies that require high-quality WSIs linked with comprehensive clinical and genetic information on colorectal cancer. Our initial findings affirm the dataset's capacity to advance diagnostic precision and foster the development of personalised treatment strategies in colorectal oncology. Data available online at https://doi.org/10.6019/S-BIAD1285.

Pre-trained language models like ChatGPT have significantly improved code generation. As these models scale up, there is an increasing need for the output to handle more intricate tasks. Moreover, in bioinformatics, generating functional programs poses additional notable challenges due to the amount of domain knowledge, the need for complicated data operations, and intricate functional dependencies between the operations. Here, we present BioCoder, a benchmark developed to evaluate existing pre-trained models in generating bioinformatics code. In relation to function-code generation, BioCoder covers potential package dependencies, class declarations, and global variables. It incorporates 1026 functions and 1243 methods in Python and Java from GitHub and 253 examples from the Rosalind Project. BioCoder incorporates a fuzz-testing framework for evaluation, and we have applied it to evaluate many models including InCoder, CodeGen, CodeGen2, SantaCoder, StarCoder, StarCoder+, InstructCodeT5+, and ChatGPT. Our detailed analysis of these models emphasizes the importance of domain knowledge, pragmatic code generation, and contextual understanding. Our dataset, benchmark, Docker images, and scripts required for testing are all available at https://github.com/gersteinlab/biocoder.

Generative search engines directly generate responses to user queries, along with in-line citations. A prerequisite trait of a trustworthy generative search engine is verifiability, i.e., systems should cite comprehensively (high citation recall; all statements are fully supported by citations) and accurately (high citation precision; every cite supports its associated statement). We conduct human evaluation to audit four popular generative search engines -- Bing Chat, NeevaAI, perplexity.ai, and YouChat -- across a diverse set of queries from a variety of sources (e.g., historical Google user queries, dynamically-collected open-ended questions on Reddit, etc.). We find that responses from existing generative search engines are fluent and appear informative, but frequently contain unsupported statements and inaccurate citations: on average, a mere 51.5% of generated sentences are fully supported by citations and only 74.5% of citations support their associated sentence. We believe that these results are concerningly low for systems that may serve as a primary tool for information-seeking users, especially given their facade of trustworthiness. We hope that our results further motivate the development of trustworthy generative search engines and help researchers and users better understand the shortcomings of existing commercial systems.

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.

There is widespread optimism that frontier Large Language Models (LLMs) and LLM-augmented systems have the potential to rapidly accelerate scientific discovery across disciplines. Today, many benchmarks exist to measure LLM knowledge and reasoning on textbook-style science questions, but few if any benchmarks are designed to evaluate language model performance on practical tasks required for scientific research, such as literature search, protocol planning, and data analysis. As a step toward building such benchmarks, we introduce the Language Agent Biology Benchmark (LAB-Bench), a broad dataset of over 2,400 multiple choice questions for evaluating AI systems on a range of practical biology research capabilities, including recall and reasoning over literature, interpretation of figures, access and navigation of databases, and comprehension and manipulation of DNA and protein sequences. Importantly, in contrast to previous scientific benchmarks, we expect that an AI system that can achieve consistently high scores on the more difficult LAB-Bench tasks would serve as a useful assistant for researchers in areas such as literature search and molecular cloning. As an initial assessment of the emergent scientific task capabilities of frontier language models, we measure performance of several against our benchmark and report results compared to human expert biology researchers. We will continue to update and expand LAB-Bench over time, and expect it to serve as a useful tool in the development of automated research systems going forward. A public subset of LAB-Bench is available for use at the following URL: https://huggingface.co/datasets/futurehouse/lab-bench

Antibodies are proteins produced by the immune system that can identify and neutralise a wide variety of antigens with high specificity and affinity, and constitute the most successful class of biotherapeutics. With the advent of next-generation sequencing, billions of antibody sequences have been collected in recent years, though their application in the design of better therapeutics has been constrained by the sheer volume and complexity of the data. To address this challenge, we present IgBert and IgT5, the best performing antibody-specific language models developed to date which can consistently handle both paired and unpaired variable region sequences as input. These models are trained comprehensively using the more than two billion unpaired sequences and two million paired sequences of light and heavy chains present in the Observed Antibody Space dataset. We show that our models outperform existing antibody and protein language models on a diverse range of design and regression tasks relevant to antibody engineering. This advancement marks a significant leap forward in leveraging machine learning, large scale data sets and high-performance computing for enhancing antibody design for therapeutic development.

High-throughput screening techniques are commonly used to obtain large quantities of data in many fields of biology. It is well known that artifacts arising from variability in the technical execution of different experimental batches within such screens confound these observations and can lead to invalid biological conclusions. It is therefore necessary to account for these batch effects when analyzing outcomes. In this paper we describe RxRx1, a biological dataset designed specifically for the systematic study of batch effect correction methods. The dataset consists of 125,510 high-resolution fluorescence microscopy images of human cells under 1,138 genetic perturbations in 51 experimental batches across 4 cell types. Visual inspection of the images alone clearly demonstrates significant batch effects. We propose a classification task designed to evaluate the effectiveness of experimental batch correction methods on these images and examine the performance of a number of correction methods on this task. Our goal in releasing RxRx1 is to encourage the development of effective experimental batch correction methods that generalize well to unseen experimental batches. The dataset can be downloaded at https://rxrx.ai.

Previous studies have shown that automated text-mining tools are becoming increasingly important for successfully unlocking variant information in scientific literature at large scale. Despite multiple attempts in the past, existing tools are still of limited recognition scope and precision. We propose tmVar 3.0: an improved variant recognition and normalization tool. Compared to its predecessors, tmVar 3.0 is able to recognize a wide spectrum of variant related entities (e.g., allele and copy number variants), and to group different variant mentions belonging to the same concept in an article for improved accuracy. Moreover, tmVar3 provides additional variant normalization options such as allele-specific identifiers from the ClinGen Allele Registry. tmVar3 exhibits a state-of-the-art performance with over 90% accuracy in F-measure in variant recognition and normalization, when evaluated on three independent benchmarking datasets. tmVar3 is freely available for download. We have also processed the entire PubMed and PMC with tmVar3 and released its annotations on our FTP. Availability: ftp://ftp.ncbi.nlm.nih.gov/pub/lu/tmVar3

Large language models, particularly GPT-3, are able to produce high quality summaries of general domain news articles in few- and zero-shot settings. However, it is unclear if such models are similarly capable in more specialized, high-stakes domains such as biomedicine. In this paper, we enlist domain experts (individuals with medical training) to evaluate summaries of biomedical articles generated by GPT-3, given zero supervision. We consider both single- and multi-document settings. In the former, GPT-3 is tasked with generating regular and plain-language summaries of articles describing randomized controlled trials; in the latter, we assess the degree to which GPT-3 is able to synthesize evidence reported across a collection of articles. We design an annotation scheme for evaluating model outputs, with an emphasis on assessing the factual accuracy of generated summaries. We find that while GPT-3 is able to summarize and simplify single biomedical articles faithfully, it struggles to provide accurate aggregations of findings over multiple documents. We release all data and annotations used in this work.

Artificial intelligence (AI)-driven methods can vastly improve the historically costly drug design process, with various generative models already in widespread use. Generative models for de novo drug design, in particular, focus on the creation of novel biological compounds entirely from scratch, representing a promising future direction. Rapid development in the field, combined with the inherent complexity of the drug design process, creates a difficult landscape for new researchers to enter. In this survey, we organize de novo drug design into two overarching themes: small molecule and protein generation. Within each theme, we identify a variety of subtasks and applications, highlighting important datasets, benchmarks, and model architectures and comparing the performance of top models. We take a broad approach to AI-driven drug design, allowing for both micro-level comparisons of various methods within each subtask and macro-level observations across different fields. We discuss parallel challenges and approaches between the two applications and highlight future directions for AI-driven de novo drug design as a whole. An organized repository of all covered sources is available at https://github.com/gersteinlab/GenAI4Drug.

As an efficient approach to understand, generate, and process natural language texts, research in natural language processing (NLP) has exhibited a rapid spread and wide adoption in recent years. Given the increasing amount of research work in this area, several NLP-related approaches have been surveyed in the research community. However, a comprehensive study that categorizes established topics, identifies trends, and outlines areas for future research remains absent to this day. Contributing to closing this gap, we have systematically classified and analyzed research papers included in the ACL Anthology. As a result, we present a structured overview of the research landscape, provide a taxonomy of fields-of-study in NLP, analyze recent developments in NLP, summarize our findings, and highlight directions for future work.

AI alignment research is the field of study dedicated to ensuring that artificial intelligence (AI) benefits humans. As machine intelligence gets more advanced, this research is becoming increasingly important. Researchers in the field share ideas across different media to speed up the exchange of information. However, this focus on speed means that the research landscape is opaque, making it difficult for young researchers to enter the field. In this project, we collected and analyzed existing AI alignment research. We found that the field is growing quickly, with several subfields emerging in parallel. We looked at the subfields and identified the prominent researchers, recurring topics, and different modes of communication in each. Furthermore, we found that a classifier trained on AI alignment research articles can detect relevant articles that we did not originally include in the dataset. We are sharing the dataset with the research community and hope to develop tools in the future that will help both established researchers and young researchers get more involved in the field.

Data of sequential nature arise in many application domains in forms of, e.g. textual data, DNA sequences, and software execution traces. Different research disciplines have developed methods to learn sequence models from such datasets: (i) in the machine learning field methods such as (hidden) Markov models and recurrent neural networks have been developed and successfully applied to a wide-range of tasks, (ii) in process mining process discovery techniques aim to generate human-interpretable descriptive models, and (iii) in the grammar inference field the focus is on finding descriptive models in the form of formal grammars. Despite their different focuses, these fields share a common goal - learning a model that accurately describes the behavior in the underlying data. Those sequence models are generative, i.e, they can predict what elements are likely to occur after a given unfinished sequence. So far, these fields have developed mainly in isolation from each other and no comparison exists. This paper presents an interdisciplinary experimental evaluation that compares sequence modeling techniques on the task of next-element prediction on four real-life sequence datasets. The results indicate that machine learning techniques that generally have no aim at interpretability in terms of accuracy outperform techniques from the process mining and grammar inference fields that aim to yield interpretable models.

Effective DNA embedding remains crucial in genomic analysis, particularly in scenarios lacking labeled data for model fine-tuning, despite the significant advancements in genome foundation models. A prime example is metagenomics binning, a critical process in microbiome research that aims to group DNA sequences by their species from a complex mixture of DNA sequences derived from potentially thousands of distinct, often uncharacterized species. To fill the lack of effective DNA embedding models, we introduce DNABERT-S, a genome foundation model that specializes in creating species-aware DNA embeddings. To encourage effective embeddings to error-prone long-read DNA sequences, we introduce Manifold Instance Mixup (MI-Mix), a contrastive objective that mixes the hidden representations of DNA sequences at randomly selected layers and trains the model to recognize and differentiate these mixed proportions at the output layer. We further enhance it with the proposed Curriculum Contrastive Learning (C^2LR) strategy. Empirical results on 18 diverse datasets showed DNABERT-S's remarkable performance. It outperforms the top baseline's performance in 10-shot species classification with just a 2-shot training while doubling the Adjusted Rand Index (ARI) in species clustering and substantially increasing the number of correctly identified species in metagenomics binning. The code, data, and pre-trained model are publicly available at https://github.com/Zhihan1996/DNABERT_S.

Advances in natural language processing and large language models have sparked growing interest in modeling DNA, often referred to as the "language of life". However, DNA modeling poses unique challenges. First, it requires the ability to process ultra-long DNA sequences while preserving single-nucleotide resolution, as individual nucleotides play a critical role in DNA function. Second, success in this domain requires excelling at both generative and understanding tasks: generative tasks hold potential for therapeutic and industrial applications, while understanding tasks provide crucial insights into biological mechanisms and diseases. To address these challenges, we propose HybriDNA, a decoder-only DNA language model that incorporates a hybrid Transformer-Mamba2 architecture, seamlessly integrating the strengths of attention mechanisms with selective state-space models. This hybrid design enables HybriDNA to efficiently process DNA sequences up to 131kb in length with single-nucleotide resolution. HybriDNA achieves state-of-the-art performance across 33 DNA understanding datasets curated from the BEND, GUE, and LRB benchmarks, and demonstrates exceptional capability in generating synthetic cis-regulatory elements (CREs) with desired properties. Furthermore, we show that HybriDNA adheres to expected scaling laws, with performance improving consistently as the model scales from 300M to 3B and 7B parameters. These findings underscore HybriDNA's versatility and its potential to advance DNA research and applications, paving the way for innovations in understanding and engineering the "language of life".

Recent advances in multi-modal algorithms have driven and been driven by the increasing availability of large image-text datasets, leading to significant strides in various fields, including computational pathology. However, in most existing medical image-text datasets, the text typically provides high-level summaries that may not sufficiently describe sub-tile regions within a large pathology image. For example, an image might cover an extensive tissue area containing cancerous and healthy regions, but the accompanying text might only specify that this image is a cancer slide, lacking the nuanced details needed for in-depth analysis. In this study, we introduce STimage-1K4M, a novel dataset designed to bridge this gap by providing genomic features for sub-tile images. STimage-1K4M contains 1,149 images derived from spatial transcriptomics data, which captures gene expression information at the level of individual spatial spots within a pathology image. Specifically, each image in the dataset is broken down into smaller sub-image tiles, with each tile paired with 15,000-30,000 dimensional gene expressions. With 4,293,195 pairs of sub-tile images and gene expressions, STimage-1K4M offers unprecedented granularity, paving the way for a wide range of advanced research in multi-modal data analysis an innovative applications in computational pathology, and beyond.

Recent progress in large language models has enabled the deployment of many generative NLP applications. At the same time, it has also led to a misleading public discourse that ``it's all been solved.'' Not surprisingly, this has in turn made many NLP researchers -- especially those at the beginning of their career -- wonder about what NLP research area they should focus on. This document is a compilation of NLP research directions that are rich for exploration, reflecting the views of a diverse group of PhD students in an academic research lab. While we identify many research areas, many others exist; we do not cover those areas that are currently addressed by LLMs but where LLMs lag behind in performance, or those focused on LLM development. We welcome suggestions for other research directions to include: https://bit.ly/nlp-era-llm

Large language models (LLMs) such as those embedded in 'chatbots' are accelerating and democratizing research by providing comprehensible information and expertise from many different fields. However, these models may also confer easy access to dual-use technologies capable of inflicting great harm. To evaluate this risk, the 'Safeguarding the Future' course at MIT tasked non-scientist students with investigating whether LLM chatbots could be prompted to assist non-experts in causing a pandemic. In one hour, the chatbots suggested four potential pandemic pathogens, explained how they can be generated from synthetic DNA using reverse genetics, supplied the names of DNA synthesis companies unlikely to screen orders, identified detailed protocols and how to troubleshoot them, and recommended that anyone lacking the skills to perform reverse genetics engage a core facility or contract research organization. Collectively, these results suggest that LLMs will make pandemic-class agents widely accessible as soon as they are credibly identified, even to people with little or no laboratory training. Promising nonproliferation measures include pre-release evaluations of LLMs by third parties, curating training datasets to remove harmful concepts, and verifiably screening all DNA generated by synthesis providers or used by contract research organizations and robotic cloud laboratories to engineer organisms or viruses.

Literature-Based Discovery (LBD) aims to discover new scientific knowledge by mining papers and generating hypotheses. Standard LBD is limited to predicting pairwise relations between discrete concepts (e.g., drug-disease links), and ignores critical contexts like experimental settings (e.g., a specific patient population where a drug is evaluated) and background motivations (e.g., to find drugs without specific side effects). We address these limitations with a novel formulation of contextualized-LBD (C-LBD): generating scientific hypotheses in natural language, while grounding them in a context that controls the hypothesis search space. We present a modeling framework using retrieval of ``inspirations'' from past scientific papers. Our evaluations reveal that GPT-4 tends to generate ideas with overall low technical depth and novelty, while our inspiration prompting approaches partially mitigate this issue. Our work represents a first step toward building language models that generate new ideas derived from scientific literature.

Medical systematic reviews can be very costly and resource intensive. We explore how Large Language Models (LLMs) can support and be trained to perform literature screening when provided with a detailed set of selection criteria. Specifically, we instruction tune LLaMA and Guanaco models to perform abstract screening for medical systematic reviews. Our best model, Bio-SIEVE, outperforms both ChatGPT and trained traditional approaches, and generalises better across medical domains. However, there remains the challenge of adapting the model to safety-first scenarios. We also explore the impact of multi-task training with Bio-SIEVE-Multi, including tasks such as PICO extraction and exclusion reasoning, but find that it is unable to match single-task Bio-SIEVE's performance. We see Bio-SIEVE as an important step towards specialising LLMs for the biomedical systematic review process and explore its future developmental opportunities. We release our models, code and a list of DOIs to reconstruct our dataset for reproducibility.

Protein Language Models (PLMs) have emerged as performant and scalable tools for predicting the functional impact and clinical significance of protein-coding variants, but they still lag experimental accuracy. Here, we present a novel fine-tuning approach to improve the performance of PLMs with experimental maps of variant effects from Deep Mutational Scanning (DMS) assays using a Normalised Log-odds Ratio (NLR) head. We find consistent improvements in a held-out protein test set, and on independent DMS and clinical variant annotation benchmarks from ProteinGym and ClinVar. These findings demonstrate that DMS is a promising source of sequence diversity and supervised training data for improving the performance of PLMs for variant effect prediction.

The development of vision-language models (VLMs) is driven by large-scale and diverse multimodal datasets. However, progress toward generalist biomedical VLMs is limited by the lack of annotated, publicly accessible datasets across biology and medicine. Existing efforts are restricted to narrow domains, missing the full diversity of biomedical knowledge encoded in scientific literature. To address this gap, we introduce BIOMEDICA, a scalable, open-source framework to extract, annotate, and serialize the entirety of the PubMed Central Open Access subset into an easy-to-use, publicly accessible dataset.Our framework produces a comprehensive archive with over 24 million unique image-text pairs from over 6 million articles. Metadata and expert-guided annotations are also provided. We demonstrate the utility and accessibility of our resource by releasing BMCA-CLIP, a suite of CLIP-style models continuously pre-trained on the BIOMEDICA dataset via streaming, eliminating the need to download 27 TB of data locally.On average, our models achieve state-of-the-art performance across 40 tasks - spanning pathology, radiology, ophthalmology, dermatology, surgery, molecular biology, parasitology, and cell biology - excelling in zero-shot classification with a 6.56% average improvement (as high as 29.8% and 17.5% in dermatology and ophthalmology, respectively), and stronger image-text retrieval, all while using 10x less compute. To foster reproducibility and collaboration, we release our codebase and dataset for the broader research community.

We study the problem of adaptively identifying patient subpopulations that benefit from a given treatment during a confirmatory clinical trial. This type of adaptive clinical trial has been thoroughly studied in biostatistics, but has been allowed only limited adaptivity so far. Here, we aim to relax classical restrictions on such designs and investigate how to incorporate ideas from the recent machine learning literature on adaptive and online experimentation to make trials more flexible and efficient. We find that the unique characteristics of the subpopulation selection problem -- most importantly that (i) one is usually interested in finding subpopulations with any treatment benefit (and not necessarily the single subgroup with largest effect) given a limited budget and that (ii) effectiveness only has to be demonstrated across the subpopulation on average -- give rise to interesting challenges and new desiderata when designing algorithmic solutions. Building on these findings, we propose AdaGGI and AdaGCPI, two meta-algorithms for subpopulation construction. We empirically investigate their performance across a range of simulation scenarios and derive insights into their (dis)advantages across different settings.

Combating bias in NLP requires bias measurement. Bias measurement is almost always achieved by using lexicons of seed terms, i.e. sets of words specifying stereotypes or dimensions of interest. This reproducibility study focuses on the original authors' main claim that the rationale for the construction of these lexicons needs thorough checking before usage, as the seeds used for bias measurement can themselves exhibit biases. The study aims to evaluate the reproducibility of the quantitative and qualitative results presented in the paper and the conclusions drawn thereof. We reproduce most of the results supporting the original authors' general claim: seed sets often suffer from biases that affect their performance as a baseline for bias metrics. Generally, our results mirror the original paper's. They are slightly different on select occasions, but not in ways that undermine the paper's general intent to show the fragility of seed sets.

The task of Prior Case Retrieval (PCR) in the legal domain is about automatically citing relevant (based on facts and precedence) prior legal cases in a given query case. To further promote research in PCR, in this paper, we propose a new large benchmark (in English) for the PCR task: IL-PCR (Indian Legal Prior Case Retrieval) corpus. Given the complex nature of case relevance and the long size of legal documents, BM25 remains a strong baseline for ranking the cited prior documents. In this work, we explore the role of events in legal case retrieval and propose an unsupervised retrieval method-based pipeline U-CREAT (Unsupervised Case Retrieval using Events Extraction). We find that the proposed unsupervised retrieval method significantly increases performance compared to BM25 and makes retrieval faster by a considerable margin, making it applicable to real-time case retrieval systems. Our proposed system is generic, we show that it generalizes across two different legal systems (Indian and Canadian), and it shows state-of-the-art performance on the benchmarks for both the legal systems (IL-PCR and COLIEE corpora).

The ability to accurately model the fitness landscape of protein sequences is critical to a wide range of applications, from quantifying the effects of human variants on disease likelihood, to predicting immune-escape mutations in viruses and designing novel biotherapeutic proteins. Deep generative models of protein sequences trained on multiple sequence alignments have been the most successful approaches so far to address these tasks. The performance of these methods is however contingent on the availability of sufficiently deep and diverse alignments for reliable training. Their potential scope is thus limited by the fact many protein families are hard, if not impossible, to align. Large language models trained on massive quantities of non-aligned protein sequences from diverse families address these problems and show potential to eventually bridge the performance gap. We introduce Tranception, a novel transformer architecture leveraging autoregressive predictions and retrieval of homologous sequences at inference to achieve state-of-the-art fitness prediction performance. Given its markedly higher performance on multiple mutants, robustness to shallow alignments and ability to score indels, our approach offers significant gain of scope over existing approaches. To enable more rigorous model testing across a broader range of protein families, we develop ProteinGym -- an extensive set of multiplexed assays of variant effects, substantially increasing both the number and diversity of assays compared to existing benchmarks.

As language models grow ever larger, the need for large-scale high-quality text datasets has never been more pressing, especially in multilingual settings. The BigScience workshop, a 1-year international and multidisciplinary initiative, was formed with the goal of researching and training large language models as a values-driven undertaking, putting issues of ethics, harm, and governance in the foreground. This paper documents the data creation and curation efforts undertaken by BigScience to assemble the Responsible Open-science Open-collaboration Text Sources (ROOTS) corpus, a 1.6TB dataset spanning 59 languages that was used to train the 176-billion-parameter BigScience Large Open-science Open-access Multilingual (BLOOM) language model. We further release a large initial subset of the corpus and analyses thereof, and hope to empower large-scale monolingual and multilingual modeling projects with both the data and the processing tools, as well as stimulate research around this large multilingual corpus.

Despite being self-supervised, protein language models have shown remarkable performance in fundamental biological tasks such as predicting impact of genetic variation on protein structure and function. The effectiveness of these models on diverse set of tasks suggests that they learn meaningful representations of fitness landscape that can be useful for downstream clinical applications. Here, we interrogate the use of these language models in characterizing known pathogenic mutations in curated, medically actionable genes through an exhaustive search of putative compensatory mutations on each variant's genetic background. Systematic analysis of the predicted effects of these compensatory mutations reveal unappreciated structural features of proteins that are missed by other structure predictors like AlphaFold. While deep mutational scan experiments provide an unbiased estimate of the mutational landscape, we encourage the community to generate and curate rescue mutation experiments to inform the design of more sophisticated co-masking strategies and leverage large language models more effectively for downstream clinical prediction tasks.

We assessed the performance of commercial Large Language Models (LLMs) GPT-3.5-Turbo and GPT-4 on tasks from the 2023 BioASQ challenge. In Task 11b Phase B, which is focused on answer generation, both models demonstrated competitive abilities with leading systems. Remarkably, they achieved this with simple zero-shot learning, grounded with relevant snippets. Even without relevant snippets, their performance was decent, though not on par with the best systems. Interestingly, the older and cheaper GPT-3.5-Turbo system was able to compete with GPT-4 in the grounded Q&A setting on factoid and list answers. In Task 11b Phase A, focusing on retrieval, query expansion through zero-shot learning improved performance, but the models fell short compared to other systems. The code needed to rerun these experiments is available through GitHub.

Motivation: The development of novel compounds targeting proteins of interest is one of the most important tasks in the pharmaceutical industry. Deep generative models have been applied to targeted molecular design and have shown promising results. Recently, target-specific molecule generation has been viewed as a translation between the protein language and the chemical language. However, such a model is limited by the availability of interacting protein-ligand pairs. On the other hand, large amounts of unlabeled protein sequences and chemical compounds are available and have been used to train language models that learn useful representations. In this study, we propose exploiting pretrained biochemical language models to initialize (i.e. warm start) targeted molecule generation models. We investigate two warm start strategies: (i) a one-stage strategy where the initialized model is trained on targeted molecule generation (ii) a two-stage strategy containing a pre-finetuning on molecular generation followed by target specific training. We also compare two decoding strategies to generate compounds: beam search and sampling. Results: The results show that the warm-started models perform better than a baseline model trained from scratch. The two proposed warm-start strategies achieve similar results to each other with respect to widely used metrics from benchmarks. However, docking evaluation of the generated compounds for a number of novel proteins suggests that the one-stage strategy generalizes better than the two-stage strategy. Additionally, we observe that beam search outperforms sampling in both docking evaluation and benchmark metrics for assessing compound quality. Availability and implementation: The source code is available at https://github.com/boun-tabi/biochemical-lms-for-drug-design and the materials are archived in Zenodo at https://doi.org/10.5281/zenodo.6832145

Discovering novel drug candidate molecules is one of the most fundamental and critical steps in drug development. Generative deep learning models, which create synthetic data given a probability distribution, have been developed with the purpose of picking completely new samples from a partially known space. Generative models offer high potential for designing de novo molecules; however, in order for them to be useful in real-life drug development pipelines, these models should be able to design target-specific molecules, which is the next step in this field. In this study, we propose DrugGEN, for the de novo design of drug candidate molecules that interact with selected target proteins. The proposed system represents compounds and protein structures as graphs and processes them via serially connected two generative adversarial networks comprising graph transformers. DrugGEN is trained using a large dataset of compounds from ChEMBL and target-specific bioactive molecules, to design effective and specific inhibitory molecules against the AKT1 protein, which has critical importance for developing treatments against various types of cancer. On fundamental benchmarks, DrugGEN models have either competitive or better performance against other methods. To assess the target-specific generation performance, we conducted further in silico analysis with molecular docking and deep learning-based bioactivity prediction. Results indicate that de novo molecules have high potential for interacting with the AKT1 protein structure in the level of its native ligand. DrugGEN can be used to design completely novel and effective target-specific drug candidate molecules for any druggable protein, given target features and a dataset of experimental bioactivities. Code base, datasets, results and trained models of DrugGEN are available at https://github.com/HUBioDataLab/DrugGEN

The integration of biomolecular modeling with natural language (BL) has emerged as a promising interdisciplinary area at the intersection of artificial intelligence, chemistry and biology. This approach leverages the rich, multifaceted descriptions of biomolecules contained within textual data sources to enhance our fundamental understanding and enable downstream computational tasks such as biomolecule property prediction. The fusion of the nuanced narratives expressed through natural language with the structural and functional specifics of biomolecules described via various molecular modeling techniques opens new avenues for comprehensively representing and analyzing biomolecules. By incorporating the contextual language data that surrounds biomolecules into their modeling, BL aims to capture a holistic view encompassing both the symbolic qualities conveyed through language as well as quantitative structural characteristics. In this review, we provide an extensive analysis of recent advancements achieved through cross modeling of biomolecules and natural language. (1) We begin by outlining the technical representations of biomolecules employed, including sequences, 2D graphs, and 3D structures. (2) We then examine in depth the rationale and key objectives underlying effective multi-modal integration of language and molecular data sources. (3) We subsequently survey the practical applications enabled to date in this developing research area. (4) We also compile and summarize the available resources and datasets to facilitate future work. (5) Looking ahead, we identify several promising research directions worthy of further exploration and investment to continue advancing the field. The related resources and contents are updating in https://github.com/QizhiPei/Awesome-Biomolecule-Language-Cross-Modeling.

Motivation: The gut microbiota has recently emerged as a key factor that underpins certain connections between diet and human health. A tremendous amount of knowledge has been amassed from experimental studies on diet, human metabolism and microbiome. However, this evidence remains mostly buried in scientific publications, and biomedical literature mining in this domain remains scarce. We developed DiMB-RE, a comprehensive corpus annotated with 15 entity types (e.g., Nutrient, Microorganism) and 13 relation types (e.g., increases, improves) capturing diet-microbiome associations. We also trained and evaluated state-of-the-art natural language processing (NLP) models for named entity, trigger, and relation extraction as well as factuality detection using DiMB-RE. Results: DiMB-RE consists of 14,450 entities and 4,206 relationships from 165 articles. While NLP models performed reasonably well for named entity recognition (0.760 F_{1}), end-to-end relation extraction performance was modest (0.356 F_{1}), partly due to missed entities and triggers as well as cross-sentence relations. Conclusions: To our knowledge, DiMB-RE is largest and most diverse dataset focusing on diet-microbiome interactions. It can serve as a benchmark corpus for biomedical literature mining. Availability: DiMB-RE and the NLP models are available at https://github.com/ScienceNLP-Lab/DiMB-RE.

Patient recruitment is challenging for clinical trials. We introduce TrialGPT, an end-to-end framework for zero-shot patient-to-trial matching with large language models. TrialGPT comprises three modules: it first performs large-scale filtering to retrieve candidate trials (TrialGPT-Retrieval); then predicts criterion-level patient eligibility (TrialGPT-Matching); and finally generates trial-level scores (TrialGPT-Ranking). We evaluate TrialGPT on three cohorts of 183 synthetic patients with over 75,000 trial annotations. TrialGPT-Retrieval can recall over 90% of relevant trials using less than 6% of the initial collection. Manual evaluations on 1,015 patient-criterion pairs show that TrialGPT-Matching achieves an accuracy of 87.3% with faithful explanations, close to the expert performance. The TrialGPT-Ranking scores are highly correlated with human judgments and outperform the best-competing models by 43.8% in ranking and excluding trials. Furthermore, our user study reveals that TrialGPT can reduce the screening time by 42.6% in patient recruitment. Overall, these results have demonstrated promising opportunities for patient-to-trial matching with TrialGPT.

Foundation models (FMs) have exhibited remarkable performance across a wide range of downstream tasks in many domains. Nevertheless, general-purpose FMs often face challenges when confronted with domain-specific problems, due to their limited access to the proprietary training data in a particular domain. In biomedicine, there are various biological modalities, such as molecules, proteins, and cells, which are encoded by the language of life and exhibit significant modality gaps with human natural language. In this paper, we introduce BioMedGPT, an open multimodal generative pre-trained transformer (GPT) for biomedicine, to bridge the gap between the language of life and human natural language. BioMedGPT allows users to easily ``communicate'' with diverse biological modalities through free text, which is the first of its kind. BioMedGPT aligns different biological modalities with natural language via a large generative language model, namely, BioMedGPT-LM. We publish BioMedGPT-10B, which unifies the feature spaces of molecules, proteins, and natural language via encoding and alignment. Through fine-tuning, BioMedGPT-10B outperforms or is on par with human and significantly larger general-purpose foundation models on the biomedical QA task. It also demonstrates promising performance in the molecule QA and protein QA tasks, which could greatly accelerate the discovery of new drugs and therapeutic targets. In addition, BioMedGPT-LM-7B is the first large generative language model based on Llama2 in the biomedical domain, therefore is commercial friendly. Both BioMedGPT-10B and BioMedGPT-LM-7B are open-sourced to the research community. In addition, we publish the datasets that are meticulously curated for the alignment of multi-modalities, i.e., PubChemQA and UniProtQA. All the models, codes, and datasets are available at https://github.com/PharMolix/OpenBioMed.

In machine learning, generative modeling aims to learn to generate new data statistically similar to the training data distribution. In this paper, we survey learning generative models under limited data, few shots and zero shot, referred to as Generative Modeling under Data Constraint (GM-DC). This is an important topic when data acquisition is challenging, e.g. healthcare applications. We discuss background, challenges, and propose two taxonomies: one on GM-DC tasks and another on GM-DC approaches. Importantly, we study interactions between different GM-DC tasks and approaches. Furthermore, we highlight research gaps, research trends, and potential avenues for future exploration. Project website: https://gmdc-survey.github.io.

Large language models have already demonstrated their formidable capabilities in general domains, ushering in a revolutionary transformation. However, exploring and exploiting the extensive knowledge of these models to comprehend multi-omics biology remains underexplored. To fill this research gap, we first introduce Biology-Instructions, the first large-scale multi-omics biological sequences-related instruction-tuning dataset including DNA, RNA, proteins, and multi-molecules, designed to bridge the gap between large language models (LLMs) and complex biological sequences-related tasks. This dataset can enhance the versatility of LLMs by integrating diverse biological sequenced-based prediction tasks with advanced reasoning capabilities, while maintaining conversational fluency. Additionally, we reveal significant performance limitations in even state-of-the-art LLMs on biological sequence-related multi-omics tasks without specialized pre-training and instruction-tuning. We further develop a strong baseline called ChatMultiOmics with a novel three-stage training pipeline, demonstrating the powerful ability to understand biology by using Biology-Instructions. Biology-Instructions and ChatMultiOmics are publicly available and crucial resources for enabling more effective integration of LLMs with multi-omics sequence analysis.

Given the dominance of dense retrievers that do not generalize well beyond their training dataset distributions, domain-specific test sets are essential in evaluating retrieval. There are few test datasets for retrieval systems intended for use by healthcare providers in a point-of-care setting. To fill this gap we have collaborated with medical professionals to create CURE, an ad-hoc retrieval test dataset for passage ranking with 2000 queries spanning 10 medical domains with a monolingual (English) and two cross-lingual (French/Spanish -> English) conditions. In this paper, we describe how CURE was constructed and provide baseline results to showcase its effectiveness as an evaluation tool. CURE is published with a Creative Commons Attribution Non Commercial 4.0 license and can be accessed on Hugging Face.

Training and evaluating language models increasingly requires the construction of meta-datasets --diverse collections of curated data with clear provenance. Natural language prompting has recently lead to improved zero-shot generalization by transforming existing, supervised datasets into a diversity of novel pretraining tasks, highlighting the benefits of meta-dataset curation. While successful in general-domain text, translating these data-centric approaches to biomedical language modeling remains challenging, as labeled biomedical datasets are significantly underrepresented in popular data hubs. To address this challenge, we introduce BigBIO a community library of 126+ biomedical NLP datasets, currently covering 12 task categories and 10+ languages. BigBIO facilitates reproducible meta-dataset curation via programmatic access to datasets and their metadata, and is compatible with current platforms for prompt engineering and end-to-end few/zero shot language model evaluation. We discuss our process for task schema harmonization, data auditing, contribution guidelines, and outline two illustrative use cases: zero-shot evaluation of biomedical prompts and large-scale, multi-task learning. BigBIO is an ongoing community effort and is available at https://github.com/bigscience-workshop/biomedical

This work delved into the realm of automatic text generation, exploring a variety of techniques ranging from traditional deterministic approaches to more modern stochastic methods. Through analysis of greedy search, beam search, top-k sampling, top-p sampling, contrastive searching, and locally typical searching, this work has provided valuable insights into the strengths, weaknesses, and potential applications of each method. Each text-generating method is evaluated using several standard metrics and a comparative study has been made on the performance of the approaches. Finally, some future directions of research in the field of automatic text generation are also identified.

Over the past decade, the revolution in single-cell sequencing has enabled the simultaneous molecular profiling of various modalities across thousands of individual cells, allowing scientists to investigate the diverse functions of complex tissues and uncover underlying disease mechanisms. Among all the analytical steps, assigning individual cells to specific types is fundamental for understanding cellular heterogeneity. However, this process is usually labor-intensive and requires extensive expert knowledge. Recent advances in large language models (LLMs) have demonstrated their ability to efficiently process and synthesize vast corpora of text to automatically extract essential biological knowledge, such as marker genes, potentially promoting more efficient and automated cell type annotations. To thoroughly evaluate the capability of modern instruction-tuned LLMs in automating the cell type identification process, we introduce SOAR, a comprehensive benchmarking study of LLMs for cell type annotation tasks in single-cell genomics. Specifically, we assess the performance of 8 instruction-tuned LLMs across 11 datasets, spanning multiple cell types and species. Our study explores the potential of LLMs to accurately classify and annotate cell types in single-cell RNA sequencing (scRNA-seq) data, while extending their application to multiomics data through cross-modality translation. Additionally, we evaluate the effectiveness of chain-of-thought (CoT) prompting techniques in generating detailed biological insights during the annotation process. The results demonstrate that LLMs can provide robust interpretations of single-cell data without requiring additional fine-tuning, advancing the automation of cell type annotation in genomics research.

This paper presents the system description of our entry for the COLING 2025 RegNLP RIRAG (Regulatory Information Retrieval and Answer Generation) challenge, focusing on leveraging advanced information retrieval and answer generation techniques in regulatory domains. We experimented with a combination of embedding models, including Stella, BGE, CDE, and Mpnet, and leveraged fine-tuning and reranking for retrieving relevant documents in top ranks. We utilized a novel approach, LeSeR, which achieved competitive results with a recall@10 of 0.8201 and map@10 of 0.6655 for retrievals. This work highlights the transformative potential of natural language processing techniques in regulatory applications, offering insights into their capabilities for implementing a retrieval augmented generation system while identifying areas for future improvement in robustness and domain adaptation.

Protein modeling is an increasingly popular area of machine learning research. Semi-supervised learning has emerged as an important paradigm in protein modeling due to the high cost of acquiring supervised protein labels, but the current literature is fragmented when it comes to datasets and standardized evaluation techniques. To facilitate progress in this field, we introduce the Tasks Assessing Protein Embeddings (TAPE), a set of five biologically relevant semi-supervised learning tasks spread across different domains of protein biology. We curate tasks into specific training, validation, and test splits to ensure that each task tests biologically relevant generalization that transfers to real-life scenarios. We benchmark a range of approaches to semi-supervised protein representation learning, which span recent work as well as canonical sequence learning techniques. We find that self-supervised pretraining is helpful for almost all models on all tasks, more than doubling performance in some cases. Despite this increase, in several cases features learned by self-supervised pretraining still lag behind features extracted by state-of-the-art non-neural techniques. This gap in performance suggests a huge opportunity for innovative architecture design and improved modeling paradigms that better capture the signal in biological sequences. TAPE will help the machine learning community focus effort on scientifically relevant problems. Toward this end, all data and code used to run these experiments are available at https://github.com/songlab-cal/tape.

Understanding the origin(s) of life (OoL) is a fundamental challenge for science in the 21st century. Research on OoL spans many disciplines, including chemistry, physics, biology, planetary sciences, computer science, mathematics and philosophy. The sheer number of different scientific perspectives relevant to the problem has resulted in the coexistence of diverse tools, techniques, data, and software in OoL studies. This has made communication between the disciplines relevant to the OoL extremely difficult because the interpretation of data, analyses, or standards of evidence can vary dramatically. Here, we hope to bridge this wide field of study by providing common ground via the consolidation of tools and techniques rather than positing a unifying view on how life emerges. We review the common tools and techniques that have been used significantly in OoL studies in recent years. In particular, we aim to identify which information is most relevant for comparing and integrating the results of experimental analyses into mathematical and computational models. This review aims to provide a baseline expectation and understanding of technical aspects of origins research, rather than being a primer on any particular topic. As such, it spans broadly -- from analytical chemistry to mathematical models -- and highlights areas of future work that will benefit from a multidisciplinary approach to tackling the mystery of life's origin. Ultimately, we hope to empower a new generation of OoL scientists by reviewing how they can investigate life's origin, rather than dictating how to think about the problem.

The rapid expansion of genomic sequence data calls for new methods to achieve robust sequence representations. Existing techniques often neglect intricate structural details, emphasizing mainly contextual information. To address this, we developed k-mer embeddings that merge contextual and structural string information by enhancing De Bruijn graphs with structural similarity connections. Subsequently, we crafted a self-supervised method based on Contrastive Learning that employs a heterogeneous Graph Convolutional Network encoder and constructs positive pairs based on node similarities. Our embeddings consistently outperform prior techniques for Edit Distance Approximation and Closest String Retrieval tasks.

Jupyter notebooks facilitate the bundling of executable code with its documentation and output in one interactive environment, and they represent a popular mechanism to document and share computational workflows. The reproducibility of computational aspects of research is a key component of scientific reproducibility but has not yet been assessed at scale for Jupyter notebooks associated with biomedical publications. We address computational reproducibility at two levels: First, using fully automated workflows, we analyzed the computational reproducibility of Jupyter notebooks related to publications indexed in PubMed Central. We identified such notebooks by mining the articles full text, locating them on GitHub and re-running them in an environment as close to the original as possible. We documented reproduction success and exceptions and explored relationships between notebook reproducibility and variables related to the notebooks or publications. Second, this study represents a reproducibility attempt in and of itself, using essentially the same methodology twice on PubMed Central over two years. Out of 27271 notebooks from 2660 GitHub repositories associated with 3467 articles, 22578 notebooks were written in Python, including 15817 that had their dependencies declared in standard requirement files and that we attempted to re-run automatically. For 10388 of these, all declared dependencies could be installed successfully, and we re-ran them to assess reproducibility. Of these, 1203 notebooks ran through without any errors, including 879 that produced results identical to those reported in the original notebook and 324 for which our results differed from the originally reported ones. Running the other notebooks resulted in exceptions. We zoom in on common problems, highlight trends and discuss potential improvements to Jupyter-related workflows associated with biomedical publications.

In recent years, groundbreaking advancements in natural language processing have culminated in the emergence of powerful large language models (LLMs), which have showcased remarkable capabilities across a vast array of domains, including the understanding, generation, and translation of natural language, and even tasks that extend beyond language processing. In this report, we delve into the performance of LLMs within the context of scientific discovery, focusing on GPT-4, the state-of-the-art language model. Our investigation spans a diverse range of scientific areas encompassing drug discovery, biology, computational chemistry (density functional theory (DFT) and molecular dynamics (MD)), materials design, and partial differential equations (PDE). Evaluating GPT-4 on scientific tasks is crucial for uncovering its potential across various research domains, validating its domain-specific expertise, accelerating scientific progress, optimizing resource allocation, guiding future model development, and fostering interdisciplinary research. Our exploration methodology primarily consists of expert-driven case assessments, which offer qualitative insights into the model's comprehension of intricate scientific concepts and relationships, and occasionally benchmark testing, which quantitatively evaluates the model's capacity to solve well-defined domain-specific problems. Our preliminary exploration indicates that GPT-4 exhibits promising potential for a variety of scientific applications, demonstrating its aptitude for handling complex problem-solving and knowledge integration tasks. Broadly speaking, we evaluate GPT-4's knowledge base, scientific understanding, scientific numerical calculation abilities, and various scientific prediction capabilities.

Clinical trial matching is a key process in health delivery and discovery. In practice, it is plagued by overwhelming unstructured data and unscalable manual processing. In this paper, we conduct a systematic study on scaling clinical trial matching using large language models (LLMs), with oncology as the focus area. Our study is grounded in a clinical trial matching system currently in test deployment at a large U.S. health network. Initial findings are promising: out of box, cutting-edge LLMs, such as GPT-4, can already structure elaborate eligibility criteria of clinical trials and extract complex matching logic (e.g., nested AND/OR/NOT). While still far from perfect, LLMs substantially outperform prior strong baselines and may serve as a preliminary solution to help triage patient-trial candidates with humans in the loop. Our study also reveals a few significant growth areas for applying LLMs to end-to-end clinical trial matching, such as context limitation and accuracy, especially in structuring patient information from longitudinal medical records.

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

This paper introduces a pioneering approach to artificial intelligence research, embodied in our O1 Replication Journey. In response to the announcement of OpenAI's groundbreaking O1 model, we embark on a transparent, real-time exploration to replicate its capabilities while reimagining the process of conducting and communicating AI research. Our methodology addresses critical challenges in modern AI research, including the insularity of prolonged team-based projects, delayed information sharing, and the lack of recognition for diverse contributions. By providing comprehensive, real-time documentation of our replication efforts, including both successes and failures, we aim to foster open science, accelerate collective advancement, and lay the groundwork for AI-driven scientific discovery. Our research progress report diverges significantly from traditional research papers, offering continuous updates, full process transparency, and active community engagement throughout the research journey. Technologically, we proposed the journey learning paradigm, which encourages models to learn not just shortcuts, but the complete exploration process, including trial and error, reflection, and backtracking. With only 327 training samples and without any additional tricks, journey learning outperformed conventional supervised learning by over 8\% on the MATH dataset, demonstrating its extremely powerful potential. We believe this to be the most crucial component of O1 technology that we have successfully decoded. We share valuable resources including technical hypotheses and insights, cognitive exploration maps, custom-developed tools, etc at https://github.com/GAIR-NLP/O1-Journey.

The increased capabilities of generative AI have dramatically expanded its possible use cases in medicine. We provide a comprehensive overview of generative AI use cases for clinicians, patients, clinical trial organizers, researchers, and trainees. We then discuss the many challenges -- including maintaining privacy and security, improving transparency and interpretability, upholding equity, and rigorously evaluating models -- which must be overcome to realize this potential, and the open research directions they give rise to.

Recent advances in generative models, including large language models (LLMs), vision language models (VLMs), and diffusion models, have accelerated the field of natural language and image processing in medicine and marked a significant paradigm shift in how biomedical models can be developed and deployed. While these models are highly adaptable to new tasks, scaling and evaluating their usage presents new challenges not addressed in previous frameworks. In particular, the ability of these models to produce useful outputs with little to no specialized training data ("zero-" or "few-shot" approaches), as well as the open-ended nature of their outputs, necessitate the development of new guidelines for robust reporting of clinical generative model research. In response to gaps in standards and best practices for the development of clinical AI tools identified by US Executive Order 141103 and several emerging national networks for clinical AI evaluation, we begin to formalize some of these guidelines by building on the original MI-CLAIM checklist. The new checklist, MI-CLAIM-GEN (Table 1), aims to address differences in training, evaluation, interpretability, and reproducibility of new generative models compared to non-generative ("predictive") AI models. This MI-CLAIM-GEN checklist also seeks to clarify cohort selection reporting with unstructured clinical data and adds additional items on alignment with ethical standards for clinical AI research.

Retrieval-Augmented Generation allows to enhance Large Language Models with external knowledge. In response to the recent popularity of generative LLMs, many RAG approaches have been proposed, which involve an intricate number of different configurations such as evaluation datasets, collections, metrics, retrievers, and LLMs. Inconsistent benchmarking poses a major challenge in comparing approaches and understanding the impact of each component in the pipeline. In this work, we study best practices that lay the groundwork for a systematic evaluation of RAG and present BERGEN, an end-to-end library for reproducible research standardizing RAG experiments. In an extensive study focusing on QA, we benchmark different state-of-the-art retrievers, rerankers, and LLMs. Additionally, we analyze existing RAG metrics and datasets. Our open-source library BERGEN is available under https://github.com/naver/bergen.

Despite its crucial role in research experiments, code correctness is often presumed only on the basis of the perceived quality of results. This assumption comes with the risk of erroneous outcomes and potentially misleading findings. To address this issue, we posit that the current focus on reproducibility should go hand in hand with the emphasis on software quality. We present a case study in which we identify and fix three bugs in widely used implementations of the state-of-the-art Conformer architecture. Through experiments on speech recognition and translation in various languages, we demonstrate that the presence of bugs does not prevent the achievement of good and reproducible results, which however can lead to incorrect conclusions that potentially misguide future research. As a countermeasure, we propose a Code-quality Checklist and release pangoliNN, a library dedicated to testing neural models, with the goal of promoting coding best practices and improving research software quality within the NLP community.

There is enormous enthusiasm and concerns in using large language models (LLMs) in healthcare, yet current assumptions are all based on general-purpose LLMs such as ChatGPT. This study develops a clinical generative LLM, GatorTronGPT, using 277 billion words of mixed clinical and English text with a GPT-3 architecture of 20 billion parameters. GatorTronGPT improves biomedical natural language processing for medical research. Synthetic NLP models trained using GatorTronGPT generated text outperform NLP models trained using real-world clinical text. Physicians Turing test using 1 (worst) to 9 (best) scale shows that there is no significant difference in linguistic readability (p = 0.22; 6.57 of GatorTronGPT compared with 6.93 of human) and clinical relevance (p = 0.91; 7.0 of GatorTronGPT compared with 6.97 of human) and that physicians cannot differentiate them (p < 0.001). This study provides insights on the opportunities and challenges of LLMs for medical research and healthcare.

Summary: GeneFEAST, implemented in Python, is a gene-centric functional enrichment analysis summarisation and visualisation tool that can be applied to large functional enrichment analysis (FEA) results arising from upstream FEA pipelines. It produces a systematic, navigable HTML report, making it easy to identify sets of genes putatively driving multiple enrichments and to explore gene-level quantitative data first used to identify input genes. Further, GeneFEAST can compare FEA results from multiple studies, making it possible, for example, to highlight patterns of gene expression amongst genes commonly differentially expressed in two sets of conditions, and giving rise to shared enrichments under those conditions. GeneFEAST offers a novel, effective way to address the complexities of linking up many overlapping FEA results to their underlying genes and data, advancing gene-centric hypotheses, and providing pivotal information for downstream validation experiments. Availability: GeneFEAST is available at https://github.com/avigailtaylor/GeneFEAST Contact: [email protected]

Scientific discovery is a complex cognitive process that has driven human knowledge and technological progress for centuries. While artificial intelligence (AI) has made significant advances in automating aspects of scientific reasoning, simulation, and experimentation, we still lack integrated AI systems capable of performing autonomous long-term scientific research and discovery. This paper examines the current state of AI for scientific discovery, highlighting recent progress in large language models and other AI techniques applied to scientific tasks. We then outline key challenges and promising research directions toward developing more comprehensive AI systems for scientific discovery, including the need for science-focused AI agents, improved benchmarks and evaluation metrics, multimodal scientific representations, and unified frameworks combining reasoning, theorem proving, and data-driven modeling. Addressing these challenges could lead to transformative AI tools to accelerate progress across disciplines towards scientific discovery.

PubTator 3.0 (https://www.ncbi.nlm.nih.gov/research/pubtator3/) is a biomedical literature resource using state-of-the-art AI techniques to offer semantic and relation searches for key concepts like proteins, genetic variants, diseases, and chemicals. It currently provides over one billion entity and relation annotations across approximately 36 million PubMed abstracts and 6 million full-text articles from the PMC open access subset, updated weekly. PubTator 3.0's online interface and API utilize these precomputed entity relations and synonyms to provide advanced search capabilities and enable large-scale analyses, streamlining many complex information needs. We showcase the retrieval quality of PubTator 3.0 using a series of entity pair queries, demonstrating that PubTator 3.0 retrieves a greater number of articles than either PubMed or Google Scholar, with higher precision in the top 20 results. We further show that integrating ChatGPT (GPT-4) with PubTator APIs dramatically improves the factuality and verifiability of its responses. In summary, PubTator 3.0 offers a comprehensive set of features and tools that allow researchers to navigate the ever-expanding wealth of biomedical literature, expediting research and unlocking valuable insights for scientific discovery.

Based on the BioBricks standard, restriction synthesis is a novel catabolic iterative DNA synthesis method that utilizes endonucleases to synthesize a query sequence from a reference sequence. In this work, the reference sequence is built from shorter subsequences by classifying them as applicable or inapplicable for the synthesis method using three different machine learning methods: Support Vector Machines (SVMs), random forest, and Convolution Neural Networks (CNNs). Before applying these methods to the data, a series of feature selection, curation, and reduction steps are applied to create an accurate and representative feature space. Following these preprocessing steps, three different pipelines are proposed to classify subsequences based on their nucleotide sequence and other relevant features corresponding to the restriction sites of over 200 endonucleases. The sensitivity using SVMs, random forest, and CNNs are 94.9%, 92.7%, 91.4%, respectively. Moreover, each method scores lower in specificity with SVMs, random forest, and CNNs resulting in 77.4%, 85.7%, and 82.4%, respectively. In addition to analyzing these results, the misclassifications in SVMs and CNNs are investigated. Across these two models, different features with a derived nucleotide specificity visually contribute more to classification compared to other features. This observation is an important factor when considering new nucleotide sensitivity features for future studies.

High-throughput drug screening -- using cell imaging or gene expression measurements as readouts of drug effect -- is a critical tool in biotechnology to assess and understand the relationship between the chemical structure and biological activity of a drug. Since large-scale screens have to be divided into multiple experiments, a key difficulty is dealing with batch effects, which can introduce systematic errors and non-biological associations in the data. We propose InfoCORE, an Information maximization approach for COnfounder REmoval, to effectively deal with batch effects and obtain refined molecular representations. InfoCORE establishes a variational lower bound on the conditional mutual information of the latent representations given a batch identifier. It adaptively reweighs samples to equalize their implied batch distribution. Extensive experiments on drug screening data reveal InfoCORE's superior performance in a multitude of tasks including molecular property prediction and molecule-phenotype retrieval. Additionally, we show results for how InfoCORE offers a versatile framework and resolves general distribution shifts and issues of data fairness by minimizing correlation with spurious features or removing sensitive attributes. The code is available at https://github.com/uhlerlab/InfoCORE.

In the pharmaceutical industry, the use of artificial intelligence (AI) has seen consistent growth over the past decade. This rise is attributed to major advancements in statistical machine learning methodologies, computational capabilities and the increased availability of large datasets. AI techniques are applied throughout different stages of drug development, ranging from drug discovery to post-marketing benefit-risk assessment. Kolluri et al. provided a review of several case studies that span these stages, featuring key applications such as protein structure prediction, success probability estimation, subgroup identification, and AI-assisted clinical trial monitoring. From a regulatory standpoint, there was a notable uptick in submissions incorporating AI components in 2021. The most prevalent therapeutic areas leveraging AI were oncology (27%), psychiatry (15%), gastroenterology (12%), and neurology (11%). The paradigm of personalized or precision medicine has gained significant traction in recent research, partly due to advancements in AI techniques hamburg2010path. This shift has had a transformative impact on the pharmaceutical industry. Departing from the traditional "one-size-fits-all" model, personalized medicine incorporates various individual factors, such as environmental conditions, lifestyle choices, and health histories, to formulate customized treatment plans. By utilizing sophisticated machine learning algorithms, clinicians and researchers are better equipped to make informed decisions in areas such as disease prevention, diagnosis, and treatment selection, thereby optimizing health outcomes for each individual.

Genetic pathways usually encode molecular mechanisms that can inform targeted interventions. It is often challenging for existing machine learning approaches to jointly model genetic pathways (higher-order features) and variants (atomic features), and present to clinicians interpretable models. In order to build more accurate and better interpretable machine learning models for genetic medicine, we introduce Pathway Augmented Nonnegative Tensor factorization for HighER-order feature learning (PANTHER). PANTHER selects informative genetic pathways that directly encode molecular mechanisms. We apply genetically motivated constrained tensor factorization to group pathways in a way that reflects molecular mechanism interactions. We then train a softmax classifier for disease types using the identified pathway groups. We evaluated PANTHER against multiple state-of-the-art constrained tensor/matrix factorization models, as well as group guided and Bayesian hierarchical models. PANTHER outperforms all state-of-the-art comparison models significantly (p<0.05). Our experiments on large scale Next Generation Sequencing (NGS) and whole-genome genotyping datasets also demonstrated wide applicability of PANTHER. We performed feature analysis in predicting disease types, which suggested insights and benefits of the identified pathway groups.

Inferring causal structure poses a combinatorial search problem that typically involves evaluating structures with a score or independence test. The resulting search is costly, and designing suitable scores or tests that capture prior knowledge is difficult. In this work, we propose to amortize causal structure learning. Rather than searching over structures, we train a variational inference model to directly predict the causal structure from observational or interventional data. This allows our inference model to acquire domain-specific inductive biases for causal discovery solely from data generated by a simulator, bypassing both the hand-engineering of suitable score functions and the search over graphs. The architecture of our inference model emulates permutation invariances that are crucial for statistical efficiency in structure learning, which facilitates generalization to significantly larger problem instances than seen during training. On synthetic data and semisynthetic gene expression data, our models exhibit robust generalization capabilities when subject to substantial distribution shifts and significantly outperform existing algorithms, especially in the challenging genomics domain. Our code and models are publicly available at: https://github.com/larslorch/avici.

We describe the SemEval task of extracting keyphrases and relations between them from scientific documents, which is crucial for understanding which publications describe which processes, tasks and materials. Although this was a new task, we had a total of 26 submissions across 3 evaluation scenarios. We expect the task and the findings reported in this paper to be relevant for researchers working on understanding scientific content, as well as the broader knowledge base population and information extraction communities.

The automation of scientific discovery has been a long-standing goal within the research community, driven by the potential to accelerate knowledge creation. While significant progress has been made using commercial large language models (LLMs) as research assistants or idea generators, the possibility of automating the entire research process with open-source LLMs remains largely unexplored. This paper explores the feasibility of using open-source post-trained LLMs as autonomous agents capable of performing the full cycle of automated research and review, from literature review and manuscript preparation to peer review and paper revision. Our iterative preference training framework consists of CycleResearcher, which conducts research tasks, and CycleReviewer, which simulates the peer review process, providing iterative feedback via reinforcement learning. To train these models, we develop two new datasets, Review-5k and Research-14k, reflecting real-world machine learning research and peer review dynamics. Our results demonstrate that CycleReviewer achieves a 26.89\% improvement in mean absolute error (MAE) over individual human reviewers in predicting paper scores, indicating that LLMs can surpass expert-level performance in research evaluation. In research, the papers generated by the CycleResearcher model achieved a score of 5.36 in simulated peer reviews, surpassing the preprint level of 5.24 from human experts and approaching the accepted paper level of 5.69. This work represents a significant step toward fully automated scientific inquiry, providing ethical safeguards and advancing AI-driven research capabilities. The code, dataset and model weight are released at http://github/minjun-zhu/Researcher.

As opposed to scaling-up protein language models (PLMs), we seek improving performance via protein-specific optimization. Although the proportionality between the language model size and the richness of its learned representations is validated, we prioritize accessibility and pursue a path of data-efficient, cost-reduced, and knowledge-guided optimization. Through over twenty experiments ranging from masking, architecture, and pre-training data, we derive insights from protein-specific experimentation into building a model that interprets the language of life, optimally. We present Ankh, the first general-purpose PLM trained on Google's TPU-v4 surpassing the state-of-the-art performance with fewer parameters (<10% for pre-training, <7% for inference, and <30% for the embedding dimension). We provide a representative range of structure and function benchmarks where Ankh excels. We further provide a protein variant generation analysis on High-N and One-N input data scales where Ankh succeeds in learning protein evolutionary conservation-mutation trends and introducing functional diversity while retaining key structural-functional characteristics. We dedicate our work to promoting accessibility to research innovation via attainable resources.

Machine learning, notably deep learning, has significantly propelled molecular investigations within the biochemical sphere. Traditionally, modeling for such research has centered around a handful of paradigms. For instance, the prediction paradigm is frequently deployed for tasks such as molecular property prediction. To enhance the generation and decipherability of purely data-driven models, scholars have integrated biochemical domain knowledge into these molecular study models. This integration has sparked a surge in paradigm transfer, which is solving one molecular learning task by reformulating it as another one. With the emergence of Large Language Models, these paradigms have demonstrated an escalating trend towards harmonized unification. In this work, we delineate a literature survey focused on knowledge-informed molecular learning from the perspective of paradigm transfer. We classify the paradigms, scrutinize their methodologies, and dissect the contribution of domain knowledge. Moreover, we encapsulate prevailing trends and identify intriguing avenues for future exploration in molecular learning.

Background: Health datasets from clinical sources do not reflect the breadth and diversity of disease in the real world, impacting research, medical education, and artificial intelligence (AI) tool development. Dermatology is a suitable area to develop and test a new and scalable method to create representative health datasets. Methods: We used Google Search advertisements to invite contributions to an open access dataset of images of dermatology conditions, demographic and symptom information. With informed contributor consent, we describe and release this dataset containing 10,408 images from 5,033 contributions from internet users in the United States over 8 months starting March 2023. The dataset includes dermatologist condition labels as well as estimated Fitzpatrick Skin Type (eFST) and Monk Skin Tone (eMST) labels for the images. Results: We received a median of 22 submissions/day (IQR 14-30). Female (66.72%) and younger (52% < age 40) contributors had a higher representation in the dataset compared to the US population, and 32.6% of contributors reported a non-White racial or ethnic identity. Over 97.5% of contributions were genuine images of skin conditions. Dermatologist confidence in assigning a differential diagnosis increased with the number of available variables, and showed a weaker correlation with image sharpness (Spearman's P values <0.001 and 0.01 respectively). Most contributions were short-duration (54% with onset < 7 days ago ) and 89% were allergic, infectious, or inflammatory conditions. eFST and eMST distributions reflected the geographical origin of the dataset. The dataset is available at github.com/google-research-datasets/scin . Conclusion: Search ads are effective at crowdsourcing images of health conditions. The SCIN dataset bridges important gaps in the availability of representative images of common skin conditions.

Hypertension, defined as blood pressure (BP) that is above normal, holds paramount significance in the realm of public health, as it serves as a critical precursor to various cardiovascular diseases (CVDs) and significantly contributes to elevated mortality rates worldwide. However, many existing BP measurement technologies and standards might be biased because they do not consider clinical outcomes, comorbidities, or demographic factors, making them inconclusive for diagnostic purposes. There is limited data-driven research focused on studying the variance in BP measurements across these variables. In this work, we employed GPT-35-turbo, a large language model (LLM), to automatically extract the mean and standard deviation values of BP for both males and females from a dataset comprising 25 million abstracts sourced from PubMed. 993 article abstracts met our predefined inclusion criteria (i.e., presence of references to blood pressure, units of blood pressure such as mmHg, and mention of biological sex). Based on the automatically-extracted information from these articles, we conducted an analysis of the variations of BP values across biological sex. Our results showed the viability of utilizing LLMs to study the BP variations across different demographic factors.

Synthesizing clinical evidence largely relies on systematic reviews of clinical trials and retrospective analyses from medical literature. However, the rapid expansion of publications presents challenges in efficiently identifying, summarizing, and updating clinical evidence. Here, we introduce TrialMind, a generative artificial intelligence (AI) pipeline for facilitating human-AI collaboration in three crucial tasks for evidence synthesis: study search, screening, and data extraction. To assess its performance, we chose published systematic reviews to build the benchmark dataset, named TrialReviewBench, which contains 100 systematic reviews and the associated 2,220 clinical studies. Our results show that TrialMind excels across all three tasks. In study search, it generates diverse and comprehensive search queries to achieve high recall rates (Ours 0.711-0.834 v.s. Human baseline 0.138-0.232). For study screening, TrialMind surpasses traditional embedding-based methods by 30% to 160%. In data extraction, it outperforms a GPT-4 baseline by 29.6% to 61.5%. We further conducted user studies to confirm its practical utility. Compared to manual efforts, human-AI collaboration using TrialMind yielded a 71.4% recall lift and 44.2% time savings in study screening and a 23.5% accuracy lift and 63.4% time savings in data extraction. Additionally, when comparing synthesized clinical evidence presented in forest plots, medical experts favored TrialMind's outputs over GPT-4's outputs in 62.5% to 100% of cases. These findings show the promise of LLM-based approaches like TrialMind to accelerate clinical evidence synthesis via streamlining study search, screening, and data extraction from medical literature, with exceptional performance improvement when working with human experts.

In modern data-driven science, reproducibility and reusability are key challenges. Scientists are well skilled in the process from data to publication. Although some publication channels require source code and data to be made accessible, rerunning and verifying experiments is usually hard due to a lack of standards. Therefore, reusing existing scientific data processing code from state-of-the-art research is hard as well. This is why we introduce CLAIMED, which has a proven track record in scientific research for addressing the repeatability and reusability issues in modern data-driven science. CLAIMED is a framework to build reusable operators and scalable scientific workflows by supporting the scientist to draw from previous work by re-composing workflows from existing libraries of coarse-grained scientific operators. Although various implementations exist, CLAIMED is programming language, scientific library, and execution environment agnostic.

During a virus's evolution,various regions of the genome are subjected to distinct levels of functional constraints.Combined with factors like codon bias and DNA repair efficiency,these constraints contribute to unique mutation patterns within the genome or a specific gene. In this project, we harnessed the power of Large Language Models(LLMs) to predict the evolution of SARS-CoV-2. By treating the mutation process from one generation to the next as a translation task, we trained a transformer model, called VirusT5, to capture the mutation patterns underlying SARS-CoV-2 evolution. We evaluated the VirusT5's ability to detect these mutation patterns including its ability to identify mutation hotspots and explored the potential of using VirusT5 to predict future virus variants. Our findings demonstrate the feasibility of using a large language model to model viral evolution as a translation process. This study establishes the groundbreaking concept of "mutation-as-translation," paving the way for new methodologies and tools for combating virus threats

Attention-based models trained on protein sequences have demonstrated incredible success at classification and generation tasks relevant for artificial intelligence-driven protein design. However, we lack a sufficient understanding of how very large-scale models and data play a role in effective protein model development. We introduce a suite of protein language models, named ProGen2, that are scaled up to 6.4B parameters and trained on different sequence datasets drawn from over a billion proteins from genomic, metagenomic, and immune repertoire databases. ProGen2 models show state-of-the-art performance in capturing the distribution of observed evolutionary sequences, generating novel viable sequences, and predicting protein fitness without additional finetuning. As large model sizes and raw numbers of protein sequences continue to become more widely accessible, our results suggest that a growing emphasis needs to be placed on the data distribution provided to a protein sequence model. We release the ProGen2 models and code at https://github.com/salesforce/progen.

This briefing paper focuses on data equity within foundation models, both in terms of the impact of Generative AI (genAI) on society and on the further development of genAI tools. GenAI promises immense potential to drive digital and social innovation, such as improving efficiency, enhancing creativity and augmenting existing data. GenAI has the potential to democratize access and usage of technologies. However, left unchecked, it could deepen inequities. With the advent of genAI significantly increasing the rate at which AI is deployed and developed, exploring frameworks for data equity is more urgent than ever. The goals of the briefing paper are threefold: to establish a shared vocabulary to facilitate collaboration and dialogue; to scope initial concerns to establish a framework for inquiry on which stakeholders can focus; and to shape future development of promising technologies. The paper represents a first step in exploring and promoting data equity in the context of genAI. The proposed definitions, framework and recommendations are intended to proactively shape the development of promising genAI technologies.

Antibodies comprise the most versatile class of binding molecules, with numerous applications in biomedicine. Computational design of antibodies involves generating novel and diverse sequences, while maintaining structural consistency. Unique to antibodies, designing the complementarity-determining region (CDR), which determines the antigen binding affinity and specificity, creates its own unique challenges. Recent deep learning models have shown impressive results, however the limited number of known antibody sequence/structure pairs frequently leads to degraded performance, particularly lacking diversity in the generated sequences. In our work we address this challenge by leveraging Model Reprogramming (MR), which repurposes pretrained models on a source language to adapt to the tasks that are in a different language and have scarce data - where it may be difficult to train a high-performing model from scratch or effectively fine-tune an existing pre-trained model on the specific task. Specifically, we introduce ReprogBert in which a pretrained English language model is repurposed for protein sequence infilling - thus considers cross-language adaptation using less data. Results on antibody design benchmarks show that our model on low-resourced antibody sequence dataset provides highly diverse CDR sequences, up to more than a two-fold increase of diversity over the baselines, without losing structural integrity and naturalness. The generated sequences also demonstrate enhanced antigen binding specificity and virus neutralization ability. Code is available at https://github.com/IBM/ReprogBERT

In the era of digital healthcare, the huge volumes of textual information generated every day in hospitals constitute an essential but underused asset that could be exploited with task-specific, fine-tuned biomedical language representation models, improving patient care and management. For such specialized domains, previous research has shown that fine-tuning models stemming from broad-coverage checkpoints can largely benefit additional training rounds over large-scale in-domain resources. However, these resources are often unreachable for less-resourced languages like Italian, preventing local medical institutions to employ in-domain adaptation. In order to reduce this gap, our work investigates two accessible approaches to derive biomedical language models in languages other than English, taking Italian as a concrete use-case: one based on neural machine translation of English resources, favoring quantity over quality; the other based on a high-grade, narrow-scoped corpus natively written in Italian, thus preferring quality over quantity. Our study shows that data quantity is a harder constraint than data quality for biomedical adaptation, but the concatenation of high-quality data can improve model performance even when dealing with relatively size-limited corpora. The models published from our investigations have the potential to unlock important research opportunities for Italian hospitals and academia. Finally, the set of lessons learned from the study constitutes valuable insights towards a solution to build biomedical language models that are generalizable to other less-resourced languages and different domain settings.

The exponential growth of knowledge and the increasing complexity of interdisciplinary research pose significant challenges for researchers, including information overload and difficulties in exploring novel ideas. The advancements in large language models (LLMs), such as GPT-4, have shown great potential in enhancing idea proposals, but how to effectively utilize large models for reasonable idea proposal has not been thoroughly explored. This paper proposes a scientific paper idea proposer (SciPIP). Based on a user-provided research background, SciPIP retrieves helpful papers from a literature database while leveraging the capabilities of LLMs to generate more novel and feasible ideas. To this end, 1) we construct a literature retrieval database, extracting lots of papers' multi-dimension information for fast access. Then, a literature retrieval method based on semantics, entity, and citation co-occurrences is proposed to search relevant literature from multiple aspects based on the user-provided background. 2) After literature retrieval, we introduce dual-path idea proposal strategies, where one path infers solutions from the retrieved literature and the other path generates original ideas through model brainstorming. We then combine the two to achieve a good balance between feasibility and originality. Through extensive experiments on the natural language processing (NLP) field, we demonstrate that SciPIP can retrieve citations similar to those of existing top conference papers and generate many ideas consistent with them. Additionally, we evaluate the originality of other ideas generated by SciPIP using large language models, further validating the effectiveness of our proposed method. The code and the database are released at https://github.com/cheerss/SciPIP.

We present a corpus of 5,000 richly annotated abstracts of medical articles describing clinical randomized controlled trials. Annotations include demarcations of text spans that describe the Patient population enrolled, the Interventions studied and to what they were Compared, and the Outcomes measured (the `PICO' elements). These spans are further annotated at a more granular level, e.g., individual interventions within them are marked and mapped onto a structured medical vocabulary. We acquired annotations from a diverse set of workers with varying levels of expertise and cost. We describe our data collection process and the corpus itself in detail. We then outline a set of challenging NLP tasks that would aid searching of the medical literature and the practice of evidence-based medicine.

Foundation models have revolutionized natural language processing and artificial intelligence, significantly enhancing how machines comprehend and generate human languages. Inspired by the success of these foundation models, researchers have developed foundation models for individual scientific domains, including small molecules, materials, proteins, DNA, and RNA. However, these models are typically trained in isolation, lacking the ability to integrate across different scientific domains. Recognizing that entities within these domains can all be represented as sequences, which together form the "language of nature", we introduce Nature Language Model (briefly, NatureLM), a sequence-based science foundation model designed for scientific discovery. Pre-trained with data from multiple scientific domains, NatureLM offers a unified, versatile model that enables various applications including: (i) generating and optimizing small molecules, proteins, RNA, and materials using text instructions; (ii) cross-domain generation/design, such as protein-to-molecule and protein-to-RNA generation; and (iii) achieving state-of-the-art performance in tasks like SMILES-to-IUPAC translation and retrosynthesis on USPTO-50k. NatureLM offers a promising generalist approach for various scientific tasks, including drug discovery (hit generation/optimization, ADMET optimization, synthesis), novel material design, and the development of therapeutic proteins or nucleotides. We have developed NatureLM models in different sizes (1 billion, 8 billion, and 46.7 billion parameters) and observed a clear improvement in performance as the model size increases.

In an effort to catalog insect biodiversity, we propose a new large dataset of hand-labelled insect images, the BIOSCAN-Insect Dataset. Each record is taxonomically classified by an expert, and also has associated genetic information including raw nucleotide barcode sequences and assigned barcode index numbers, which are genetically-based proxies for species classification. This paper presents a curated million-image dataset, primarily to train computer-vision models capable of providing image-based taxonomic assessment, however, the dataset also presents compelling characteristics, the study of which would be of interest to the broader machine learning community. Driven by the biological nature inherent to the dataset, a characteristic long-tailed class-imbalance distribution is exhibited. Furthermore, taxonomic labelling is a hierarchical classification scheme, presenting a highly fine-grained classification problem at lower levels. Beyond spurring interest in biodiversity research within the machine learning community, progress on creating an image-based taxonomic classifier will also further the ultimate goal of all BIOSCAN research: to lay the foundation for a comprehensive survey of global biodiversity. This paper introduces the dataset and explores the classification task through the implementation and analysis of a baseline classifier.

We study the problem of extrapolative controlled generation, i.e., generating sequences with attribute values beyond the range seen in training. This task is of significant importance in automated design, especially drug discovery, where the goal is to design novel proteins that are better (e.g., more stable) than existing sequences. Thus, by definition, the target sequences and their attribute values are out of the training distribution, posing challenges to existing methods that aim to directly generate the target sequence. Instead, in this work, we propose Iterative Controlled Extrapolation (ICE) which iteratively makes local edits to a sequence to enable extrapolation. We train the model on synthetically generated sequence pairs that demonstrate small improvement in the attribute value. Results on one natural language task (sentiment analysis) and two protein engineering tasks (ACE2 stability and AAV fitness) show that ICE considerably outperforms state-of-the-art approaches despite its simplicity. Our code and models are available at: https://github.com/vishakhpk/iter-extrapolation.

The rapid expansion of scientific literature in computer science presents challenges in tracking research trends and extracting key insights. Existing datasets provide metadata but lack structured summaries that capture core contributions and methodologies. We introduce CS-PaperSum, a large-scale dataset of 91,919 papers from 31 top-tier computer science conferences, enriched with AI-generated structured summaries using ChatGPT. To assess summary quality, we conduct embedding alignment analysis and keyword overlap analysis, demonstrating strong preservation of key concepts. We further present a case study on AI research trends, highlighting shifts in methodologies and interdisciplinary crossovers, including the rise of self-supervised learning, retrieval-augmented generation, and multimodal AI. Our dataset enables automated literature analysis, research trend forecasting, and AI-driven scientific discovery, providing a valuable resource for researchers, policymakers, and scientific information retrieval systems.

We propose ParaSCI, the first large-scale paraphrase dataset in the scientific field, including 33,981 paraphrase pairs from ACL (ParaSCI-ACL) and 316,063 pairs from arXiv (ParaSCI-arXiv). Digging into characteristics and common patterns of scientific papers, we construct this dataset though intra-paper and inter-paper methods, such as collecting citations to the same paper or aggregating definitions by scientific terms. To take advantage of sentences paraphrased partially, we put up PDBERT as a general paraphrase discovering method. The major advantages of paraphrases in ParaSCI lie in the prominent length and textual diversity, which is complementary to existing paraphrase datasets. ParaSCI obtains satisfactory results on human evaluation and downstream tasks, especially long paraphrase generation.

People increasingly search online for answers to their medical questions but the rate at which medical questions are asked online significantly exceeds the capacity of qualified people to answer them. This leaves many questions unanswered or inadequately answered. Many of these questions are not unique, and reliable identification of similar questions would enable more efficient and effective question answering schema. COVID-19 has only exacerbated this problem. Almost every government agency and healthcare organization has tried to meet the informational need of users by building online FAQs, but there is no way for people to ask their question and know if it is answered on one of these pages. While many research efforts have focused on the problem of general question similarity, these approaches do not generalize well to domains that require expert knowledge to determine semantic similarity, such as the medical domain. In this paper, we show how a double fine-tuning approach of pretraining a neural network on medical question-answer pairs followed by fine-tuning on medical question-question pairs is a particularly useful intermediate task for the ultimate goal of determining medical question similarity. While other pretraining tasks yield an accuracy below 78.7% on this task, our model achieves an accuracy of 82.6% with the same number of training examples, an accuracy of 80.0% with a much smaller training set, and an accuracy of 84.5% when the full corpus of medical question-answer data is used. We also describe a currently live system that uses the trained model to match user questions to COVID-related FAQs.

False assumptions about sex and gender are deeply embedded in the medical system, including that they are binary, static, and concordant. Machine learning researchers must understand the nature of these assumptions in order to avoid perpetuating them. In this perspectives piece, we identify three common mistakes that researchers make when dealing with sex/gender data: "sex confusion", the failure to identity what sex in a dataset does or doesn't mean; "sex obsession", the belief that sex, specifically sex assigned at birth, is the relevant variable for most applications; and "sex/gender slippage", the conflation of sex and gender even in contexts where only one or the other is known. We then discuss how these pitfalls show up in machine learning studies based on electronic health record data, which is commonly used for everything from retrospective analysis of patient outcomes to the development of algorithms to predict risk and administer care. Finally, we offer a series of recommendations about how machine learning researchers can produce both research and algorithms that more carefully engage with questions of sex/gender, better serving all patients, including transgender people.

Chemical similarity searches are widely used in-silico methods for identifying new drug-like molecules. These methods have historically relied on structure-based comparisons to compute molecular similarity. Here, we use a chemical language model to create a vector-based chemical search. We extend implementations by creating a prompt engineering strategy that utilizes two different chemical string representation algorithms: one for the query and the other for the database. We explore this method by reviewing the search results from five drug-like query molecules (penicillin G, nirmatrelvir, zidovudine, lysergic acid diethylamide, and fentanyl) and three dye-like query molecules (acid blue 25, avobenzone, and 2-diphenylaminocarbazole). We find that this novel method identifies molecules that are functionally similar to the query, indicated by the associated patent literature, and that many of these molecules are structurally distinct from the query, making them unlikely to be found with traditional chemical similarity search methods. This method may aid in the discovery of novel structural classes of molecules that achieve target functionality.

Research has a long history of discussing what is superior in predicting certain outcomes: statistical methods or the human brain. This debate has repeatedly been sparked off by the remarkable technological advances in the field of artificial intelligence (AI), such as solving tasks like object and speech recognition, achieving significant improvements in accuracy through deep-learning algorithms (Goodfellow et al. 2016), or combining various methods of computational intelligence, such as fuzzy logic, genetic algorithms, and case-based reasoning (Medsker 2012). One of the implicit promises that underlie these advancements is that machines will 1 day be capable of performing complex tasks or may even supersede humans in performing these tasks. This triggers new heated debates of when machines will ultimately replace humans (McAfee and Brynjolfsson 2017). While previous research has proved that AI performs well in some clearly defined tasks such as playing chess, playing Go or identifying objects on images, it is doubted that the development of an artificial general intelligence (AGI) which is able to solve multiple tasks at the same time can be achieved in the near future (e.g., Russell and Norvig 2016). Moreover, the use of AI to solve complex business problems in organizational contexts occurs scarcely, and applications for AI that solve complex problems remain mainly in laboratory settings instead of being implemented in practice. Since the road to AGI is still a long one, we argue that the most likely paradigm for the division of labor between humans and machines in the next decades is Hybrid Intelligence. This concept aims at using the complementary strengths of human intelligence and AI, so that they can perform better than each of the two could separately (e.g., Kamar 2016).

Advancements in high-throughput technologies have led to a shift from traditional hypothesis-driven methodologies to data-driven approaches. Multi-omics refers to the integrative analysis of data derived from multiple 'omes', such as genomics, proteomics, transcriptomics, metabolomics, and microbiomics. This approach enables a comprehensive understanding of biological systems by capturing different layers of biological information. Deep learning methods are increasingly utilized to integrate multi-omics data, offering insights into molecular interactions and enhancing research into complex diseases. However, these models, with their numerous interconnected layers and nonlinear relationships, often function as black boxes, lacking transparency in decision-making processes. To overcome this challenge, explainable artificial intelligence (xAI) methods are crucial for creating transparent models that allow clinicians to interpret and work with complex data more effectively. This review explores how xAI can improve the interpretability of deep learning models in multi-omics research, highlighting its potential to provide clinicians with clear insights, thereby facilitating the effective application of such models in clinical settings.

With the recent advances in natural language processing (NLP), a vast number of applications have emerged across various use cases. Among the plethora of NLP applications, many academic researchers are motivated to do work that has a positive social impact, in line with the recent initiatives of NLP for Social Good (NLP4SG). However, it is not always obvious to researchers how their research efforts are tackling today's big social problems. Thus, in this paper, we introduce NLP4SGPAPERS, a scientific dataset with three associated tasks that can help identify NLP4SG papers and characterize the NLP4SG landscape by: (1) identifying the papers that address a social problem, (2) mapping them to the corresponding UN Sustainable Development Goals (SDGs), and (3) identifying the task they are solving and the methods they are using. Using state-of-the-art NLP models, we address each of these tasks and use them on the entire ACL Anthology, resulting in a visualization workspace that gives researchers a comprehensive overview of the field of NLP4SG. Our website is available at https://nlp4sg.vercel.app . We released our data at https://huggingface.co/datasets/feradauto/NLP4SGPapers and code at https://github.com/feradauto/nlp4sg .

This paper presents a comprehensive study of Retrieval-Augmented Generation (RAG), tracing its evolution from foundational concepts to the current state of the art. RAG combines retrieval mechanisms with generative language models to enhance the accuracy of outputs, addressing key limitations of LLMs. The study explores the basic architecture of RAG, focusing on how retrieval and generation are integrated to handle knowledge-intensive tasks. A detailed review of the significant technological advancements in RAG is provided, including key innovations in retrieval-augmented language models and applications across various domains such as question-answering, summarization, and knowledge-based tasks. Recent research breakthroughs are discussed, highlighting novel methods for improving retrieval efficiency. Furthermore, the paper examines ongoing challenges such as scalability, bias, and ethical concerns in deployment. Future research directions are proposed, focusing on improving the robustness of RAG models, expanding the scope of application of RAG models, and addressing societal implications. This survey aims to serve as a foundational resource for researchers and practitioners in understanding the potential of RAG and its trajectory in natural language processing.

The digitization of medical records ushered in a new era of big data to clinical science, and with it the possibility that data could be shared, to multiply insights beyond what investigators could abstract from paper records. The need to share individual-level medical data to accelerate innovation in precision medicine continues to grow, and has never been more urgent, as scientists grapple with the COVID-19 pandemic. However, enthusiasm for the use of big data has been tempered by a fully appropriate concern for patient autonomy and privacy. That is, the ability to extract private or confidential information about an individual, in practice, renders it difficult to share data, since significant infrastructure and data governance must be established before data can be shared. Although HIPAA provided de-identification as an approved mechanism for data sharing, linkage attacks were identified as a major vulnerability. A variety of mechanisms have been established to avoid leaking private information, such as field suppression or abstraction, strictly limiting the amount of information that can be shared, or employing mathematical techniques such as differential privacy. Another approach, which we focus on here, is creating synthetic data that mimics the underlying data. For synthetic data to be a useful mechanism in support of medical innovation and a proxy for real-world evidence, one must demonstrate two properties of the synthetic dataset: (1) any analysis on the real data must be matched by analysis of the synthetic data (statistical fidelity) and (2) the synthetic data must preserve privacy, with minimal risk of re-identification (privacy guarantee). In this paper we propose a framework for quantifying the statistical fidelity and privacy preservation properties of synthetic datasets and demonstrate these metrics for synthetic data generated by Syntegra technology.

In the field of language modeling, models augmented with retrieval components have emerged as a promising solution to address several challenges faced in the natural language processing (NLP) field, including knowledge grounding, interpretability, and scalability. Despite the primary focus on NLP, we posit that the paradigm of retrieval-enhancement can be extended to a broader spectrum of machine learning (ML) such as computer vision, time series prediction, and computational biology. Therefore, this work introduces a formal framework of this paradigm, Retrieval-Enhanced Machine Learning (REML), by synthesizing the literature in various domains in ML with consistent notations which is missing from the current literature. Also, we found that while a number of studies employ retrieval components to augment their models, there is a lack of integration with foundational Information Retrieval (IR) research. We bridge this gap between the seminal IR research and contemporary REML studies by investigating each component that comprises the REML framework. Ultimately, the goal of this work is to equip researchers across various disciplines with a comprehensive, formally structured framework of retrieval-enhanced models, thereby fostering interdisciplinary future research.

We survey clinical document corpora, with focus on German textual data. Due to rigid data privacy legislation in Germany these resources, with only few exceptions, are stored in safe clinical data spaces and locked against clinic-external researchers. This situation stands in stark contrast with established workflows in the field of natural language processing where easy accessibility and reuse of data collections are common practice. Hence, alternative corpus designs have been examined to escape from this data poverty. Besides machine translation of English clinical datasets and the generation of synthetic corpora with fictitious clinical contents, several other types of domain proxies have come up as substitutes for authentic clinical documents. Common instances of close proxies are medical journal publications, clinical therapy guidelines, drug labels, etc., more distant proxies include online encyclopedic medical articles or medical contents from social media channels. After PRISM-conformant screening of 359 hits from four bibliographic systems, 75 relevant documents were finally selected for this review and 59 distinct corpora were determined. We identified 24 real clinical corpora (from 40 publications) out of which only 5 are publicly distributable. 2 translations of real corpora and 3 synthetic ones complement the set of clinical corpora. 14 corpora were categorized as close domain proxies, 16 as distant ones. There is a clear divide between the large number of non-accessible authentic clinical German-language corpora and their publicly accessible substitutes: translated or synthetic, close or more distant proxies. So on first sight, the data bottleneck seems broken. Intuitively yet, differences in genre-specific writing style, wording and medical domain expertise in this typological space are also obvious. This raises the question how valid alternative corpus designs really are.

Biomedical research is growing at such an exponential pace that scientists, researchers, and practitioners are no more able to cope with the amount of published literature in the domain. The knowledge presented in the literature needs to be systematized in such a way that claims and hypotheses can be easily found, accessed, and validated. Knowledge graphs can provide such a framework for semantic knowledge representation from literature. However, in order to build a knowledge graph, it is necessary to extract knowledge as relationships between biomedical entities and normalize both entities and relationship types. In this paper, we present and compare few rule-based and machine learning-based (Naive Bayes, Random Forests as examples of traditional machine learning methods and DistilBERT, PubMedBERT, T5 and SciFive-based models as examples of modern deep learning transformers) methods for scalable relationship extraction from biomedical literature, and for the integration into the knowledge graphs. We examine how resilient are these various methods to unbalanced and fairly small datasets. Our experiments show that transformer-based models handle well both small (due to pre-training on a large dataset) and unbalanced datasets. The best performing model was the PubMedBERT-based model fine-tuned on balanced data, with a reported F1-score of 0.92. DistilBERT-based model followed with F1-score of 0.89, performing faster and with lower resource requirements. BERT-based models performed better then T5-based generative models.

In molecular research, simulation \& design of molecules are key areas with significant implications for drug development, material science, and other fields. Current classical computational power falls inadequate to simulate any more than small molecules, let alone protein chains on hundreds of peptide. Therefore these experiment are done physically in wet-lab, but it takes a lot of time \& not possible to examine every molecule due to the size of the search area, tens of billions of dollars are spent every year in these research experiments. Molecule simulation \& design has lately advanced significantly by machine learning models, A fresh perspective on the issue of chemical synthesis is provided by deep generative models for graph-structured data. By optimising differentiable models that produce molecular graphs directly, it is feasible to avoid costly search techniques in the discrete and huge space of chemical structures. But these models also suffer from computational limitations when dimensions become huge and consume huge amount of resources. Quantum Generative machine learning in recent years have shown some empirical results promising significant advantages over classical counterparts.

With the introduction of ChatGPT, Large Language Models (LLMs) have received enormous attention in healthcare. Despite their potential benefits, researchers have underscored various ethical implications. While individual instances have drawn much attention, the debate lacks a systematic overview of practical applications currently researched and ethical issues connected to them. Against this background, this work aims to map the ethical landscape surrounding the current stage of deployment of LLMs in medicine and healthcare. Electronic databases and preprint servers were queried using a comprehensive search strategy. Studies were screened and extracted following a modified rapid review approach. Methodological quality was assessed using a hybrid approach. For 53 records, a meta-aggregative synthesis was performed. Four fields of applications emerged and testify to a vivid exploration phase. Advantages of using LLMs are attributed to their capacity in data analysis, personalized information provisioning, support in decision-making, mitigating information loss and enhancing information accessibility. However, we also identifies recurrent ethical concerns connected to fairness, bias, non-maleficence, transparency, and privacy. A distinctive concern is the tendency to produce harmful misinformation or convincingly but inaccurate content. A recurrent plea for ethical guidance and human oversight is evident. Given the variety of use cases, it is suggested that the ethical guidance debate be reframed to focus on defining what constitutes acceptable human oversight across the spectrum of applications. This involves considering diverse settings, varying potentials for harm, and different acceptable thresholds for performance and certainty in healthcare. In addition, a critical inquiry is necessary to determine the extent to which the current experimental use of LLMs is necessary and justified.

Drug discovery typically consists of multiple steps, including identifying a target protein key to a disease's etiology, validating that interacting with this target could prevent symptoms or cure the disease, discovering a small molecule or biologic therapeutic to interact with it, and optimizing the candidate molecule through a complex landscape of required properties. Drug discovery related tasks often involve prediction and generation while considering multiple entities that potentially interact, which poses a challenge for typical AI models. For this purpose we present MAMMAL - Molecular Aligned Multi-Modal Architecture and Language - a method that we applied to create a versatile multi-task foundation model ibm/biomed.omics.bl.sm.ma-ted-458m that learns from large-scale biological datasets (2 billion samples) across diverse modalities, including proteins, small molecules, and genes. We introduce a prompt syntax that supports a wide range of classification, regression, and generation tasks. It allows combining different modalities and entity types as inputs and/or outputs. Our model handles combinations of tokens and scalars and enables the generation of small molecules and proteins, property prediction, and transcriptomic lab test predictions. We evaluated the model on 11 diverse downstream tasks spanning different steps within a typical drug discovery pipeline, where it reaches new SOTA in 9 tasks and is comparable to SOTA in 2 tasks. This performance is achieved while using a unified architecture serving all tasks, in contrast to the original SOTA performance achieved using tailored architectures. The model code and pretrained weights are publicly available at https://github.com/BiomedSciAI/biomed-multi-alignment and https://huggingface.co/ibm/biomed.omics.bl.sm.ma-ted-458m.

Concerns about the reproducibility of deep learning research are more prominent than ever, with no clear solution in sight. The relevance of machine learning research can only be improved if we also employ empirical rigor that incorporates reproducibility guidelines, especially so in the medical imaging field. The Medical Imaging with Deep Learning (MIDL) conference has made advancements in this direction by advocating open access, and recently also recommending authors to make their code public - both aspects being adopted by the majority of the conference submissions. This helps the reproducibility of the methods, however, there is currently little or no support for further evaluation of these supplementary material, making them vulnerable to poor quality, which affects the impact of the entire submission. We have evaluated all accepted full paper submissions to MIDL between 2018 and 2022 using established, but slightly adjusted guidelines on reproducibility and the quality of the public repositories. The evaluations show that publishing repositories and using public datasets are becoming more popular, which helps traceability, but the quality of the repositories has not improved over the years, leaving room for improvement in every aspect of designing repositories. Merely 22% of all submissions contain a repository that were deemed repeatable using our evaluations. From the commonly encountered issues during the evaluations, we propose a set of guidelines for machine learning-related research for medical imaging applications, adjusted specifically for future submissions to MIDL.

Recent advancements in machine learning research, i.e., deep learning, introduced methods that excel conventional algorithms as well as humans in several complex tasks, ranging from detection of objects in images and speech recognition to playing difficult strategic games. However, the current methodology of machine learning research and consequently, implementations of the real-world applications of such algorithms, seems to have a recurring HARKing (Hypothesizing After the Results are Known) issue. In this work, we elaborate on the algorithmic, economic and social reasons and consequences of this phenomenon. We present examples from current common practices of conducting machine learning research (e.g. avoidance of reporting negative results) and failure of generalization ability of the proposed algorithms and datasets in actual real-life usage. Furthermore, a potential future trajectory of machine learning research and development from the perspective of accountable, unbiased, ethical and privacy-aware algorithmic decision making is discussed. We would like to emphasize that with this discussion we neither claim to provide an exhaustive argumentation nor blame any specific institution or individual on the raised issues. This is simply a discussion put forth by us, insiders of the machine learning field, reflecting on us.

In common law jurisdictions, legal practitioners rely on precedents to construct arguments, in line with the doctrine of stare decisis. As the number of cases grow over the years, prior case retrieval (PCR) has garnered significant attention. Besides lacking real-world scale, existing PCR datasets do not simulate a realistic setting, because their queries use complete case documents while only masking references to prior cases. The query is thereby exposed to legal reasoning not yet available when constructing an argument for an undecided case as well as spurious patterns left behind by citation masks, potentially short-circuiting a comprehensive understanding of case facts and legal principles. To address these limitations, we introduce a PCR dataset based on judgements from the European Court of Human Rights (ECtHR), which explicitly separate facts from arguments and exhibit precedential practices, aiding us to develop this PCR dataset to foster systems' comprehensive understanding. We benchmark different lexical and dense retrieval approaches with various negative sampling strategies, adapting them to deal with long text sequences using hierarchical variants. We found that difficulty-based negative sampling strategies were not effective for the PCR task, highlighting the need for investigation into domain-specific difficulty criteria. Furthermore, we observe performance of the dense models degrade with time and calls for further research into temporal adaptation of retrieval models. Additionally, we assess the influence of different views , Halsbury's and Goodhart's, in practice in ECtHR jurisdiction using PCR task.

Generative tasks about molecules, including but not limited to molecule generation, are crucial for drug discovery and material design, and have consistently attracted significant attention. In recent years, diffusion models have emerged as an impressive class of deep generative models, sparking extensive research and leading to numerous studies on their application to molecular generative tasks. Despite the proliferation of related work, there remains a notable lack of up-to-date and systematic surveys in this area. Particularly, due to the diversity of diffusion model formulations, molecular data modalities, and generative task types, the research landscape is challenging to navigate, hindering understanding and limiting the area's growth. To address this, this paper conducts a comprehensive survey of diffusion model-based molecular generative methods. We systematically review the research from the perspectives of methodological formulations, data modalities, and task types, offering a novel taxonomy. This survey aims to facilitate understanding and further flourishing development in this area. The relevant papers are summarized at: https://github.com/AzureLeon1/awesome-molecular-diffusion-models.

In recent years, the rapid advancement of Large Language Models (LLMs) has transformed the landscape of scientific research, offering unprecedented support across various stages of the research cycle. This paper presents the first systematic survey dedicated to exploring how LLMs are revolutionizing the scientific research process. We analyze the unique roles LLMs play across four critical stages of research: hypothesis discovery, experiment planning and implementation, scientific writing, and peer reviewing. Our review comprehensively showcases the task-specific methodologies and evaluation benchmarks. By identifying current challenges and proposing future research directions, this survey not only highlights the transformative potential of LLMs, but also aims to inspire and guide researchers and practitioners in leveraging LLMs to advance scientific inquiry. Resources are available at the following repository: https://github.com/du-nlp-lab/LLM4SR

The COVID-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on COVID-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 200K times and has served as the basis of many COVID-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and describe several shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for COVID-19.

Vectors are universal mathematical objects that can represent text, images, speech, or a mix of these data modalities. That happens regardless of whether data is represented by hand-crafted features or learnt embeddings. Collect a large enough quantity of such vectors and the question of retrieval becomes urgently relevant: Finding vectors that are more similar to a query vector. This monograph is concerned with the question above and covers fundamental concepts along with advanced data structures and algorithms for vector retrieval. In doing so, it recaps this fascinating topic and lowers barriers of entry into this rich area of research.

In an era of increasing pressure to achieve sustainable agriculture, the optimization of livestock feed for enhancing yield and minimizing environmental impact is a paramount objective. This study presents a pioneering approach towards this goal, using rumen microbiome data to predict the efficacy of feed additives in dairy cattle. We collected an extensive dataset that includes methane emissions from 2,190 Holstein cows distributed across 34 distinct sites. The cows were divided into control and experimental groups in a double-blind, unbiased manner, accounting for variables such as age, days in lactation, and average milk yield. The experimental groups were administered one of four leading commercial feed additives: Agolin, Kexxtone, Allimax, and Relyon. Methane emissions were measured individually both before the administration of additives and over a subsequent 12-week period. To develop our predictive model for additive efficacy, rumen microbiome samples were collected from 510 cows from the same herds prior to the study's onset. These samples underwent deep metagenomic shotgun sequencing, yielding an average of 15.7 million reads per sample. Utilizing innovative artificial intelligence techniques we successfully estimated the efficacy of these feed additives across different farms. The model's robustness was further confirmed through validation with independent cohorts, affirming its generalizability and reliability. Our results underscore the transformative capability of using targeted feed additive strategies to both optimize dairy yield and milk composition, and to significantly reduce methane emissions. Specifically, our predictive model demonstrates a scenario where its application could guide the assignment of additives to farms where they are most effective. In doing so, we could achieve an average potential reduction of over 27\% in overall emissions.

We consider the problem of predicting gene expressions from DNA sequences. A key challenge of this task is to find the regulatory elements that control gene expressions. Here, we introduce Seq2Exp, a Sequence to Expression network explicitly designed to discover and extract regulatory elements that drive target gene expression, enhancing the accuracy of the gene expression prediction. Our approach captures the causal relationship between epigenomic signals, DNA sequences and their associated regulatory elements. Specifically, we propose to decompose the epigenomic signals and the DNA sequence conditioned on the causal active regulatory elements, and apply an information bottleneck with the Beta distribution to combine their effects while filtering out non-causal components. Our experiments demonstrate that Seq2Exp outperforms existing baselines in gene expression prediction tasks and discovers influential regions compared to commonly used statistical methods for peak detection such as MACS3. The source code is released as part of the AIRS library (https://github.com/divelab/AIRS/).

Scientific documents record research findings and valuable human knowledge, comprising a vast corpus of high-quality data. Leveraging multi-modality data extracted from these documents and assessing large models' abilities to handle scientific document-oriented tasks is therefore meaningful. Despite promising advancements, large models still perform poorly on multi-page scientific document extraction and understanding tasks, and their capacity to process within-document data formats such as charts and equations remains under-explored. To address these issues, we present DocGenome, a structured document benchmark constructed by annotating 500K scientific documents from 153 disciplines in the arXiv open-access community, using our custom auto-labeling pipeline. DocGenome features four key characteristics: 1) Completeness: It is the first dataset to structure data from all modalities including 13 layout attributes along with their LaTeX source codes. 2) Logicality: It provides 6 logical relationships between different entities within each scientific document. 3) Diversity: It covers various document-oriented tasks, including document classification, visual grounding, document layout detection, document transformation, open-ended single-page QA and multi-page QA. 4) Correctness: It undergoes rigorous quality control checks conducted by a specialized team. We conduct extensive experiments to demonstrate the advantages of DocGenome and objectively evaluate the performance of large models on our benchmark.

Identifying disease phenotypes from electronic health records (EHRs) is critical for numerous secondary uses. Manually encoding physician knowledge into rules is particularly challenging for rare diseases due to inadequate EHR coding, necessitating review of clinical notes. Large language models (LLMs) offer promise in text understanding but may not efficiently handle real-world clinical documentation. We propose a zero-shot LLM-based method enriched by retrieval-augmented generation and MapReduce, which pre-identifies disease-related text snippets to be used in parallel as queries for the LLM to establish diagnosis. We show that this method as applied to pulmonary hypertension (PH), a rare disease characterized by elevated arterial pressures in the lungs, significantly outperforms physician logic rules (F_1 score of 0.62 vs. 0.75). This method has the potential to enhance rare disease cohort identification, expanding the scope of robust clinical research and care gap identification.

Software engineers are increasingly adding semantic search capabilities to applications using a strategy known as Retrieval Augmented Generation (RAG). A RAG system involves finding documents that semantically match a query and then passing the documents to a large language model (LLM) such as ChatGPT to extract the right answer using an LLM. RAG systems aim to: a) reduce the problem of hallucinated responses from LLMs, b) link sources/references to generated responses, and c) remove the need for annotating documents with meta-data. However, RAG systems suffer from limitations inherent to information retrieval systems and from reliance on LLMs. In this paper, we present an experience report on the failure points of RAG systems from three case studies from separate domains: research, education, and biomedical. We share the lessons learned and present 7 failure points to consider when designing a RAG system. The two key takeaways arising from our work are: 1) validation of a RAG system is only feasible during operation, and 2) the robustness of a RAG system evolves rather than designed in at the start. We conclude with a list of potential research directions on RAG systems for the software engineering community.

Information retrieval (IR) is essential in biomedical knowledge acquisition and clinical decision support. While recent progress has shown that language model encoders perform better semantic retrieval, training such models requires abundant query-article annotations that are difficult to obtain in biomedicine. As a result, most biomedical IR systems only conduct lexical matching. In response, we introduce BioCPT, a first-of-its-kind Contrastively Pre-trained Transformer model for zero-shot biomedical IR. To train BioCPT, we collected an unprecedented scale of 255 million user click logs from PubMed. With such data, we use contrastive learning to train a pair of closely-integrated retriever and re-ranker. Experimental results show that BioCPT sets new state-of-the-art performance on five biomedical IR tasks, outperforming various baselines including much larger models such as GPT-3-sized cpt-text-XL. In addition, BioCPT also generates better biomedical article and sentence representations for semantic evaluations. As such, BioCPT can be readily applied to various real-world biomedical IR tasks. BioCPT API and code are publicly available at https://github.com/ncbi/BioCPT.

Scientific literature searches are often exploratory, whereby users are not yet familiar with a particular field or concept but are interested in learning more about it. However, existing systems for scientific literature search are typically tailored to keyword-based lookup searches, limiting the possibilities for exploration. We propose NLP-KG, a feature-rich system designed to support the exploration of research literature in unfamiliar natural language processing (NLP) fields. In addition to a semantic search, NLP-KG allows users to easily find survey papers that provide a quick introduction to a field of interest. Further, a Fields of Study hierarchy graph enables users to familiarize themselves with a field and its related areas. Finally, a chat interface allows users to ask questions about unfamiliar concepts or specific articles in NLP and obtain answers grounded in knowledge retrieved from scientific publications. Our system provides users with comprehensive exploration possibilities, supporting them in investigating the relationships between different fields, understanding unfamiliar concepts in NLP, and finding relevant research literature. Demo, video, and code are available at: https://github.com/NLP-Knowledge-Graph/NLP-KG-WebApp.