Demystifying Large Language Models for Medicine: A Primer

Large language models (LLMs) represent a transformative class of AI tools capable of revolutionizing various aspects of healthcare by generating human-like responses across diverse contexts and adapting to novel tasks following human instructions. Their potential application spans a broad range of medical tasks, such as clinical documentation, matching patients to clinical trials, and answering medical questions. In this primer paper, we propose an actionable guideline to help healthcare professionals more efficiently utilize LLMs in their work, along with a set of best practices. This approach consists of several main phases, including formulating the task, choosing LLMs, prompt engineering, fine-tuning, and deployment. We start with the discussion of critical considerations in identifying healthcare tasks that align with the core capabilities of LLMs and selecting models based on the selected task and data, performance requirements, and model interface. We then review the strategies, such as prompt engineering and fine-tuning, to adapt standard LLMs to specialized medical tasks. Deployment considerations, including regulatory compliance, ethical guidelines, and continuous monitoring for fairness and bias, are also discussed. By providing a structured step-by-step methodology, this tutorial aims to equip healthcare professionals with the tools necessary to effectively integrate LLMs into clinical practice, ensuring that these powerful technologies are applied in a safe, reliable, and impactful manner.

EnzChemRED, a rich enzyme chemistry relation extraction dataset

Expert curation is essential to capture knowledge of enzyme functions from the scientific literature in FAIR open knowledgebases but cannot keep pace with the rate of new discoveries and new publications. In this work we present EnzChemRED, for Enzyme Chemistry Relation Extraction Dataset, a new training and benchmarking dataset to support the development of Natural Language Processing (NLP) methods such as (large) language models that can assist enzyme curation. EnzChemRED consists of 1,210 expert curated PubMed abstracts in which enzymes and the chemical reactions they catalyze are annotated using identifiers from the UniProt Knowledgebase (UniProtKB) and the ontology of Chemical Entities of Biological Interest (ChEBI). We show that fine-tuning pre-trained language models with EnzChemRED can significantly boost their ability to identify mentions of proteins and chemicals in text (Named Entity Recognition, or NER) and to extract the chemical conversions in which they participate (Relation Extraction, or RE), with average F1 score of 86.30% for NER, 86.66% for RE for chemical conversion pairs, and 83.79% for RE for chemical conversion pairs and linked enzymes. We combine the best performing methods after fine-tuning using EnzChemRED to create an end-to-end pipeline for knowledge extraction from text and apply this to abstracts at PubMed scale to create a draft map of enzyme functions in literature to guide curation efforts in UniProtKB and the reaction knowledgebase Rhea. The EnzChemRED corpus is freely available at https://ftp.expasy.org/databases/rhea/nlp/.

PubTator 3.0: an AI-powered Literature Resource for Unlocking Biomedical Knowledge

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.

PubMed and Beyond: Recent Advances and Best Practices in Biomedical Literature Search

Biomedical research yields a wealth of information, much of which is only accessible through the literature. Consequently, literature search is an essential tool for building on prior knowledge in clinical and biomedical research. Although recent improvements in artificial intelligence have expanded functionality beyond keyword-based search, these advances may be unfamiliar to clinicians and researchers. In response, we present a survey of literature search tools tailored to both general and specific information needs in biomedicine, with the objective of helping readers efficiently fulfill their information needs. We first examine the widely used PubMed search engine, discussing recent improvements and continued challenges. We then describe literature search tools catering to five specific information needs: 1. Identifying high-quality clinical research for evidence-based medicine. 2. Retrieving gene-related information for precision medicine and genomics. 3. Searching by meaning, including natural language questions. 4. Locating related articles with literature recommendation. 5. Mining literature to discover associations between concepts such as diseases and genetic variants. Additionally, we cover practical considerations and best practices for choosing and using these tools. Finally, we provide a perspective on the future of literature search engines, considering recent breakthroughs in large language models such as ChatGPT. In summary, our survey provides a comprehensive view of biomedical literature search functionalities with 36 publicly available tools.

AIONER: All-in-one scheme-based biomedical named entity recognition using deep learning

Biomedical named entity recognition (BioNER) seeks to automatically recognize biomedical entities in natural language text, serving as a necessary foundation for downstream text mining tasks and applications such as information extraction and question answering. Manually labeling training data for the BioNER task is costly, however, due to the significant domain expertise required for accurate annotation. The resulting data scarcity causes current BioNER approaches to be prone to overfitting, to suffer from limited generalizability, and to address a single entity type at a time (e.g., gene or disease). We therefore propose a novel all-in-one (AIO) scheme that uses external data from existing annotated resources to improve generalization. We further present AIONER, a general-purpose BioNER tool based on cutting-edge deep learning and our AIO schema. We evaluate AIONER on 14 BioNER benchmark tasks and show that AIONER is effective, robust, and compares favorably to other state-of-the-art approaches such as multi-task learning. We further demonstrate the practical utility of AIONER in three independent tasks to recognize entity types not previously seen in training data, as well as the advantages of AIONER over existing methods for processing biomedical text at a large scale (e.g., the entire PubMed data).

LitCovid in 2022: an information resource for the COVID-19 literature

LitCovid (https://www.ncbi.nlm.nih.gov/research/coronavirus/), first launched in February 2020, is a first-of-its-kind literature hub for tracking up-to-date published research on COVID-19. The number of articles in LitCovid has increased from 55,000 to ~300,000 over the past two and half years, with a consistent growth rate of ~10,000 articles per month. In addition to the rapid literature growth, the COVID-19 pandemic has evolved dramatically. For instance, the Omicron variant has now accounted for over 98% of new infections in the U.S. In response to the continuing evolution of the COVID-19 pandemic, this article describes significant updates to LitCovid over the last two years. First, we introduced the Long Covid collection consisting of the articles on COVID-19 survivors experiencing ongoing multisystemic symptoms, including respiratory issues, cardiovascular disease, cognitive impairment, and profound fatigue. Second, we provided new annotations on the latest COVID-19 strains and vaccines mentioned in the literature. Third, we improved several existing features with more accurate machine learning algorithms for annotating topics and classifying articles relevant to COVID-19. LitCovid has been widely used with millions of accesses by users worldwide on various information needs and continues to play a critical role in collecting, curating, and standardizing the latest knowledge on the COVID-19 literature.

Comprehensive identification of Long Covid articles with human-in-the-loop machine learning

A significant percentage of COVID-19 survivors experience ongoing multisystemic symptoms that often affect daily living, a condition known as Long Covid or post-acute-sequelae of SARS-CoV-2 infection. However, identifying Long Covid articles is challenging since articles refer to the condition using a variety of less common terms or refrain from naming it at all. We developed an iterative human-in-the-loop machine learning framework designed to effectively leverage the data available and make the most efficient use of human labels. Specifically, our approach combines data programming with active learning into a robust ensemble model. Evaluating our model on a holdout set demonstrates over three times the sensitivity of other methods. We apply our model to PubMed to create the Long Covid collection, and demonstrate that (1) most Long Covid articles do not refer to Long Covid by any name (2) when the condition is named, the name used most frequently in the biomedical literature is Long Covid, and (3) Long Covid is associated with disorders in a wide variety of body systems. The Long Covid collection is updated weekly and is searchable online at the LitCovid portal: https://www.ncbi.nlm.nih.gov/research/coronavirus/docsum?filters=e_condition.LongCovid

Multi-label classification for biomedical literature: an overview of the BioCreative VII LitCovid Track for COVID-19 literature topic annotations

The COVID-19 pandemic has been severely impacting global society since December 2019. Massive research has been undertaken to understand the characteristics of the virus and design vaccines and drugs. The related findings have been reported in biomedical literature at a rate of about 10,000 articles on COVID-19 per month. Such rapid growth significantly challenges manual curation and interpretation. For instance, LitCovid is a literature database of COVID-19-related articles in PubMed, which has accumulated more than 200,000 articles with millions of accesses each month by users worldwide. One primary curation task is to assign up to eight topics (e.g., Diagnosis and Treatment) to the articles in LitCovid. Despite the continuing advances in biomedical text mining methods, few have been dedicated to topic annotations in COVID-19 literature. To close the gap, we organized the BioCreative LitCovid track to call for a community effort to tackle automated topic annotation for COVID-19 literature. The BioCreative LitCovid dataset, consisting of over 30,000 articles with manually reviewed topics, was created for training and testing. It is one of the largest multilabel classification datasets in biomedical scientific literature. 19 teams worldwide participated and made 80 submissions in total. Most teams used hybrid systems based on transformers. The highest performing submissions achieved 0.8875, 0.9181, and 0.9394 for macro F1-score, micro F1-score, and instance-based F1-score, respectively. The level of participation and results demonstrate a successful track and help close the gap between dataset curation and method development. The dataset is publicly available via https://ftp.ncbi.nlm.nih.gov/pub/lu/LitCovid/biocreative/ for benchmarking and further development.

A Comprehensive Dictionary and Term Variation Analysis for COVID-19 and SARS-CoV-2

The number of unique terms in the scientific literature used to refer to either SARS-CoV-2 or COVID-19 is remarkably large and has continued to increase rapidly despite well-established standardized terms. This high degree of term variation makes high recall identification of these important entities difficult. In this manuscript we present an extensive dictionary of terms used in the literature to refer to SARS-CoV-2 and COVID-19. We use a rule-based approach to iteratively generate new term variants, then locate these variants in a large text corpus. We compare our dictionary to an extensive collection of terminological resources, demonstrating that our resource provides a substantial number of additional terms. We use our dictionary to analyze the usage of SARS-CoV-2 and COVID-19 terms over time and show that the number of unique terms continues to grow rapidly. Our dictionary is freely available at https://github.com/ncbi-nlp/CovidTermVar.

Navigating the landscape of COVID-19 research through literature analysis: A bird's eye view

Timely access to accurate scientific literature in the battle with the ongoing COVID-19 pandemic is critical. This unprecedented public health risk has motivated research towards understanding the disease in general, identifying drugs to treat the disease, developing potential vaccines, etc. This has given rise to a rapidly growing body of literature that doubles in number of publications every 20 days as of May 2020. Providing medical professionals with means to quickly analyze the literature and discover growing areas of knowledge is necessary for addressing their question and information needs. In this study we analyze the LitCovid collection, 13,369 COVID-19 related articles found in PubMed as of May 15th, 2020 with the purpose of examining the landscape of literature and presenting it in a format that facilitates information navigation and understanding. We do that by applying state-of-the-art named entity recognition, classification, clustering and other NLP techniques. By applying NER tools, we capture relevant bioentities (such as diseases, internal body organs, etc.) and assess the strength of their relationship with COVID-19 by the extent they are discussed in the corpus. We also collect a variety of symptoms and co-morbidities discussed in reference to COVID-19. Our clustering algorithm identifies topics represented by groups of related terms, and computes clusters corresponding to documents associated with the topic terms. Among the topics we observe several that persist through the duration of multiple weeks and have numerous associated documents, as well several that appear as emerging topics with fewer documents. All the tools and data are publicly available, and this framework can be applied to any literature collection. Taken together, these analyses produce a comprehensive, synthesized view of COVID-19 research to facilitate knowledge discovery from literature.