Opportunities and challenges for ChatGPT and large language models in biomedicine and health.

ChatGPT has drawn considerable attention from both the general public and domain experts with its remarkable text generation capabilities. This has subsequently led to the emergence of diverse applications in the field of biomedicine and health. In this work, we examine the diverse applications of large language models (LLMs), such as ChatGPT, in biomedicine and health. Specifically, we explore the areas of biomedical information retrieval, question answering, medical text summarization, information extraction and medical education and investigate whether LLMs possess the transformative power to revolutionize these tasks or whether the distinct complexities of biomedical domain presents unique challenges. Following an extensive literature survey, we find that significant advances have been made in the field of text generation tasks, surpassing the previous state-of-the-art methods. For other applications, the advances have been modest. Overall, LLMs have not yet revolutionized biomedicine, but recent rapid progress indicates that such methods hold great potential to provide valuable means for accelerating discovery and improving health. We also find that the use of LLMs, like ChatGPT, in the fields of biomedicine and health entails various risks and challenges, including fabricated information in its generated responses, as well as legal and privacy concerns associated with sensitive patient data. We believe this survey can provide a comprehensive and timely overview to biomedical researchers and healthcare practitioners on the opportunities and challenges associated with using ChatGPT and other LLMs for transforming biomedicine and health.

Evolving use of ancestry, ethnicity, and race in genetics research-A survey spanning seven decades.

To inform continuous and rigorous reflection about the description of human populations in genomics research, this study investigates the historical and contemporary use of the terms "ancestry," "ethnicity," "race," and other population labels in The American Journal of Human Genetics from 1949 to 2018. We characterize these terms' frequency of use and assess their odds of co-occurrence with a set of social and genetic topical terms. Throughout The Journal's 70-year history, "ancestry" and "ethnicity" have increased in use, appearing in 33% and 26% of articles in 2009-2018, while the use of "race" has decreased, occurring in 4% of articles in 2009-2018. Although its overall use has declined, the odds of "race" appearing in the presence of "ethnicity" has increased relative to the odds of occurring in its absence. Forms of population descriptors "Caucasian" and "Negro" have largely disappeared from The Journal (<1% of articles in 2009-2018). Conversely, the continental labels "African," "Asian," and "European" have increased in use and appear in 18%, 14%, and 42% of articles from 2009-2018, respectively. Decreasing uses of the terms "race," "Caucasian," and "Negro" are indicative of a transition away from the field's history of explicitly biological race science; at the same time, the increasing use of "ancestry," "ethnicity," and continental labels should serve to motivate ongoing reflection as the terminology used to describe genetic variation continues to evolve.

GNorm2: an improved gene name recognition and normalization system.

MOTIVATION: Gene name normalization is an important yet highly complex task in biomedical text mining research, as gene names can be highly ambiguous and may refer to different genes in different species or share similar names with other bioconcepts. This poses a challenge for accurately identifying and linking gene mentions to their corresponding entries in databases such as NCBI Gene or UniProt. While there has been a body of literature on the gene normalization task, few have addressed all of these challenges or make their solutions publicly available to the scientific community. RESULTS: Building on the success of GNormPlus, we have created GNorm2: a more advanced tool with optimized functions and improved performance. GNorm2 integrates a range of advanced deep learning-based methods, resulting in the highest levels of accuracy and efficiency for gene recognition and normalization to date. Our tool is freely available for download. AVAILABILITY AND IMPLEMENTATION: https://github.com/ncbi/GNorm2.

TeamTat: a collaborative text annotation tool.

Manually annotated data is key to developing text-mining and information-extraction algorithms. However, human annotation requires considerable time, effort and expertise. Given the rapid growth of biomedical literature, it is paramount to build tools that facilitate speed and maintain expert quality. While existing text annotation tools may provide user-friendly interfaces to domain experts, limited support is available for figure display, project management, and multi-user team annotation. In response, we developed TeamTat (https://www.teamtat.org), a web-based annotation tool (local setup available), equipped to manage team annotation projects engagingly and efficiently. TeamTat is a novel tool for managing multi-user, multi-label document annotation, reflecting the entire production life cycle. Project managers can specify annotation schema for entities and relations and select annotator(s) and distribute documents anonymously to prevent bias. Document input format can be plain text, PDF or BioC (uploaded locally or automatically retrieved from PubMed/PMC), and output format is BioC with inline annotations. TeamTat displays figures from the full text for the annotator's convenience. Multiple users can work on the same document independently in their workspaces, and the team manager can track task completion. TeamTat provides corpus quality assessment via inter-annotator agreement statistics, and a user-friendly interface convenient for annotation review and inter-annotator disagreement resolution to improve corpus quality.

NLM-Gene, a richly annotated gold standard dataset for gene entities that addresses ambiguity and multi-species gene recognition.

The automatic recognition of gene names and their corresponding database identifiers in biomedical text is an important first step for many downstream text-mining applications. While current methods for tagging gene entities have been developed for biomedical literature, their performance on species other than human is substantially lower due to the lack of annotation data. We therefore present the NLM-Gene corpus, a high-quality manually annotated corpus for genes developed at the US National Library of Medicine (NLM), covering ambiguous gene names, with an average of 29 gene mentions (10 unique identifiers) per document, and a broader representation of different species (including Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Arabidopsis thaliana, Danio rerio, etc.) when compared to previous gene annotation corpora. NLM-Gene consists of 550 PubMed abstracts from 156 biomedical journals, doubly annotated by six experienced NLM indexers, randomly paired for each document to control for bias. The annotators worked in three annotation rounds until they reached complete agreement. This gold-standard corpus can serve as a benchmark to develop & test new gene text mining algorithms. Using this new resource, we have developed a new gene finding algorithm based on deep learning which improved both on precision and recall from existing tools. The NLM-Gene annotated corpus is freely available at ftp://ftp.ncbi.nlm.nih.gov/pub/lu/NLMGene. We have also applied this tool to the entire PubMed/PMC with their results freely accessible through our web-based tool PubTator (www.ncbi.nlm.nih.gov/research/pubtator).

The biomedical relationship corpus of the BioRED track at the BioCreative VIII challenge and workshop.

The automatic recognition of biomedical relationships is an important step in the semantic understanding of the information contained in the unstructured text of the published literature. The BioRED track at BioCreative VIII aimed to foster the development of such methods by providing the participants the BioRED-BC8 corpus, a collection of 1000 PubMed documents manually curated for diseases, gene/proteins, chemicals, cell lines, gene variants, and species, as well as pairwise relationships between them which are disease-gene, chemical-gene, disease-variant, gene-gene, chemical-disease, chemical-chemical, chemical-variant, and variant-variant. Furthermore, relationships are categorized into the following semantic categories: positive correlation, negative correlation, binding, conversion, drug interaction, comparison, cotreatment, and association. Unlike most of the previous publicly available corpora, all relationships are expressed at the document level as opposed to the sentence level, and as such, the entities are normalized to the corresponding concept identifiers of the standardized vocabularies, namely, diseases and chemicals are normalized to MeSH, genes (and proteins) to National Center for Biotechnology Information (NCBI) Gene, species to NCBI Taxonomy, cell lines to Cellosaurus, and gene/protein variants to Single Nucleotide Polymorphism Database. Finally, each annotated relationship is categorized as 'novel' depending on whether it is a novel finding or experimental verification in the publication it is expressed in. This distinction helps differentiate novel findings from other relationships in the same text that provides known facts and/or background knowledge. The BioRED-BC8 corpus uses the previous BioRED corpus of 600 PubMed articles as the training dataset and includes a set of newly published 400 articles to serve as the test data for the challenge. All test articles were manually annotated for the BioCreative VIII challenge by expert biocurators at the National Library of Medicine, using the original annotation guidelines, where each article is doubly annotated in a three-round annotation process until full agreement is reached between all curators. This manuscript details the characteristics of the BioRED-BC8 corpus as a critical resource for biomedical named entity recognition and relation extraction. Using this new resource, we have demonstrated advancements in biomedical text-mining algorithm development. Database URL: https://codalab.lisn.upsaclay.fr/competitions/16381.

The overview of the BioRED (Biomedical Relation Extraction Dataset) track at BioCreative VIII.

The BioRED track at BioCreative VIII calls for a community effort to identify, semantically categorize, and highlight the novelty factor of the relationships between biomedical entities in unstructured text. Relation extraction is crucial for many biomedical natural language processing (NLP) applications, from drug discovery to custom medical solutions. The BioRED track simulates a real-world application of biomedical relationship extraction, and as such, considers multiple biomedical entity types, normalized to their specific corresponding database identifiers, as well as defines relationships between them in the documents. The challenge consisted of two subtasks: (i) in Subtask 1, participants were given the article text and human expert annotated entities, and were asked to extract the relation pairs, identify their semantic type and the novelty factor, and (ii) in Subtask 2, participants were given only the article text, and were asked to build an end-to-end system that could identify and categorize the relationships and their novelty. We received a total of 94 submissions from 14 teams worldwide. The highest F-score performances achieved for the Subtask 1 were: 77.17% for relation pair identification, 58.95% for relation type identification, 59.22% for novelty identification, and 44.55% when evaluating all of the above aspects of the comprehensive relation extraction. The highest F-score performances achieved for the Subtask 2 were: 55.84% for relation pair, 43.03% for relation type, 42.74% for novelty, and 32.75% for comprehensive relation extraction. The entire BioRED track dataset and other challenge materials are available at https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/ and https://codalab.lisn.upsaclay.fr/competitions/13377 and https://codalab.lisn.upsaclay.fr/competitions/13378. Database URL: https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/https://codalab.lisn.upsaclay.fr/competitions/13377https://codalab.lisn.upsaclay.fr/competitions/13378.

Comprehensively identifying 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 scientific articles relevant to Long Covid is challenging since there is no standardized or consensus terminology. We developed an iterative human-in-the-loop machine learning framework combining data programming with active learning into a robust ensemble model, demonstrating higher specificity and considerably higher sensitivity than other methods. Analysis of the Long Covid Collection shows 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 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.

Opportunities and Challenges for ChatGPT and Large Language Models in Biomedicine and Health.

ChatGPT has drawn considerable attention from both the general public and domain experts with its remarkable text generation capabilities. This has subsequently led to the emergence of diverse applications in the field of biomedicine and health. In this work, we examine the diverse applications of large language models (LLMs), such as ChatGPT, in biomedicine and health. Specifically we explore the areas of biomedical information retrieval, question answering, medical text summarization, information extraction, and medical education, and investigate whether LLMs possess the transformative power to revolutionize these tasks or whether the distinct complexities of biomedical domain presents unique challenges. Following an extensive literature survey, we find that significant advances have been made in the field of text generation tasks, surpassing the previous state-of-the-art methods. For other applications, the advances have been modest. Overall, LLMs have not yet revolutionized biomedicine, but recent rapid progress indicates that such methods hold great potential to provide valuable means for accelerating discovery and improving health. We also find that the use of LLMs, like ChatGPT, in the fields of biomedicine and health entails various risks and challenges, including fabricated information in its generated responses, as well as legal and privacy concerns associated with sensitive patient data. We believe this survey can provide a comprehensive and timely overview to biomedical researchers and healthcare practitioners on the opportunities and challenges associated with using ChatGPT and other LLMs for transforming biomedicine and health.

Chemical identification and indexing in full-text articles: an overview of the NLM-Chem track at BioCreative VII.

The BioCreative National Library of Medicine (NLM)-Chem track calls for a community effort to fine-tune automated recognition of chemical names in the biomedical literature. Chemicals are one of the most searched biomedical entities in PubMed, and-as highlighted during the coronavirus disease 2019 pandemic-their identification may significantly advance research in multiple biomedical subfields. While previous community challenges focused on identifying chemical names mentioned in titles and abstracts, the full text contains valuable additional detail. We, therefore, organized the BioCreative NLM-Chem track as a community effort to address automated chemical entity recognition in full-text articles. The track consisted of two tasks: (i) chemical identification and (ii) chemical indexing. The chemical identification task required predicting all chemicals mentioned in recently published full-text articles, both span [i.e. named entity recognition (NER)] and normalization (i.e. entity linking), using Medical Subject Headings (MeSH). The chemical indexing task required identifying which chemicals reflect topics for each article and should therefore appear in the listing of MeSH terms for the document in the MEDLINE article indexing. This manuscript summarizes the BioCreative NLM-Chem track and post-challenge experiments. We received a total of 85 submissions from 17 teams worldwide. The highest performance achieved for the chemical identification task was 0.8672 F-score (0.8759 precision and 0.8587 recall) for strict NER performance and 0.8136 F-score (0.8621 precision and 0.7702 recall) for strict normalization performance. The highest performance achieved for the chemical indexing task was 0.6073 F-score (0.7417 precision and 0.5141 recall). This community challenge demonstrated that (i) the current substantial achievements in deep learning technologies can be utilized to improve automated prediction accuracy further and (ii) the chemical indexing task is substantially more challenging. We look forward to further developing biomedical text-mining methods to respond to the rapid growth of biomedical literature. The NLM-Chem track dataset and other challenge materials are publicly available at https://ftp.ncbi.nlm.nih.gov/pub/lu/BC7-NLM-Chem-track/. Database URL https://ftp.ncbi.nlm.nih.gov/pub/lu/BC7-NLM-Chem-track/.

Assigning species information to corresponding genes by a sequence labeling framework.

The automatic assignment of species information to the corresponding genes in a research article is a critically important step in the gene normalization task, whereby a gene mention is normalized and linked to a database record or an identifier by a text-mining algorithm. Existing methods typically rely on heuristic rules based on gene and species co-occurrence in the article, but their accuracy is suboptimal. We therefore developed a high-performance method, using a novel deep learning-based framework, to identify whether there is a relation between a gene and a species. Instead of the traditional binary classification framework in which all possible pairs of genes and species in the same article are evaluated, we treat the problem as a sequence labeling task such that only a fraction of the pairs needs to be considered. Our benchmarking results show that our approach obtains significantly higher performance compared to that of the rule-based baseline method for the species assignment task (from 65.8-81.3% in accuracy). The source code and data for species assignment are freely available. Database URL https://github.com/ncbi/SpeciesAssignment.

NLM-Chem-BC7: manually annotated full-text resources for chemical entity annotation and indexing in biomedical articles.

The automatic recognition of chemical names and their corresponding database identifiers in biomedical text is an important first step for many downstream text-mining applications. The task is even more challenging when considering the identification of these entities in the article's full text and, furthermore, the identification of candidate substances for that article's metadata [Medical Subject Heading (MeSH) article indexing]. The National Library of Medicine (NLM)-Chem track at BioCreative VII aimed to foster the development of algorithms that can predict with high quality the chemical entities in the biomedical literature and further identify the chemical substances that are candidates for article indexing. As a result of this challenge, the NLM-Chem track produced two comprehensive, manually curated corpora annotated with chemical entities and indexed with chemical substances: the chemical identification corpus and the chemical indexing corpus. The NLM-Chem BioCreative VII (NLM-Chem-BC7) Chemical Identification corpus consists of 204 full-text PubMed Central (PMC) articles, fully annotated for chemical entities by 12 NLM indexers for both span (i.e. named entity recognition) and normalization (i.e. entity linking) using MeSH. This resource was used for the training and testing of the Chemical Identification task to evaluate the accuracy of algorithms in predicting chemicals mentioned in recently published full-text articles. The NLM-Chem-BC7 Chemical Indexing corpus consists of 1333 recently published PMC articles, equipped with chemical substance indexing by manual experts at the NLM. This resource was used for the evaluation of the Chemical Indexing task, which evaluated the accuracy of algorithms in predicting the chemicals that should be indexed, i.e. appear in the listing of MeSH terms for the document. This set was further enriched after the challenge in two ways: (i) 11 NLM indexers manually verified each of the candidate terms appearing in the prediction results of the challenge participants, but not in the MeSH indexing, and the chemical indexing terms appearing in the MeSH indexing list, but not in the prediction results, and (ii) the challenge organizers algorithmically merged the chemical entity annotations in the full text for all predicted chemical entities and used a statistical approach to keep those with the highest degree of confidence. As a result, the NLM-Chem-BC7 Chemical Indexing corpus is a gold-standard corpus for chemical indexing of journal articles and a silver-standard corpus for chemical entity identification in full-text journal articles. Together, these resources are currently the most comprehensive resources for chemical entity recognition, and we demonstrate improvements in the chemical entity recognition algorithms. We detail the characteristics of these novel resources and make them available for the community. Database URL: https://ftp.ncbi.nlm.nih.gov/pub/lu/NLM-Chem-BC7-corpus/.

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

The coronavirus disease 2019 (COVID-19) pandemic has been severely impacting global society since December 2019. The related findings such as vaccine and drug development 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. The annotated topics have been widely used for navigating the COVID literature, rapidly locating articles of interest and other downstream studies. However, annotating the topics has been the bottleneck of manual curation. 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 multi-label classification datasets in biomedical scientific literature. Nineteen 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. Notably, these scores are substantially higher (e.g. 12%, higher for macro F1-score) than the corresponding scores of the state-of-art multi-label classification method. 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. Database URL https://ftp.ncbi.nlm.nih.gov/pub/lu/LitCovid/biocreative/.

NLM-Chem, a new resource for chemical entity recognition in PubMed full text literature.

Automatically identifying chemical and drug names in scientific publications advances information access for this important class of entities in a variety of biomedical disciplines by enabling improved retrieval and linkage to related concepts. While current methods for tagging chemical entities were developed for the article title and abstract, their performance in the full article text is substantially lower. However, the full text frequently contains more detailed chemical information, such as the properties of chemical compounds, their biological effects and interactions with diseases, genes and other chemicals. We therefore present the NLM-Chem corpus, a full-text resource to support the development and evaluation of automated chemical entity taggers. The NLM-Chem corpus consists of 150 full-text articles, doubly annotated by ten expert NLM indexers, with ~5000 unique chemical name annotations, mapped to ~2000 MeSH identifiers. We also describe a substantially improved chemical entity tagger, with automated annotations for all of PubMed and PMC freely accessible through the PubTator web-based interface and API. The NLM-Chem corpus is freely available.

PDC - a probabilistic distributional clustering algorithm: a case study on suicide articles in PubMed.

The need to organize a large collection in a manner that facilitates human comprehension is crucial given the ever-increasing volumes of information. In this work, we present PDC (probabilistic distributional clustering), a novel algorithm that, given a document collection, computes disjoint term sets representing topics in the collection. The algorithm relies on probabilities of word co-occurrences to partition the set of terms appearing in the collection of documents into disjoint groups of related terms. In this work, we also present an environment to visualize the computed topics in the term space and retrieve the most related PubMed articles for each group of terms. We illustrate the algorithm by applying it to PubMed documents on the topic of suicide. Suicide is a major public health problem identified as the tenth leading cause of death in the US. In this application, our goal is to provide a global view of the mental health literature pertaining to the subject of suicide, and through this, to help create a rich environment of multifaceted data to guide health care researchers in their endeavor to better understand the breadth, depth and scope of the problem. We demonstrate the usefulness of the proposed algorithm by providing a web portal that allows mental health researchers to peruse the suicide-related literature in PubMed.

PubMed Text Similarity Model and its application to curation efforts in the Conserved Domain Database.

This study proposes a text similarity model to help biocuration efforts of the Conserved Domain Database (CDD). CDD is a curated resource that catalogs annotated multiple sequence alignment models for ancient domains and full-length proteins. These models allow for fast searching and quick identification of conserved motifs in protein sequences via Reverse PSI-BLAST. In addition, CDD curators prepare summaries detailing the function of these conserved domains and specific protein families, based on published peer-reviewed articles. To facilitate information access for database users, it is desirable to specifically identify the referenced articles that support the assertions of curator-composed sentences. Moreover, CDD curators desire an alert system that scans the newly published literature and proposes related articles of relevance to the existing CDD records. Our approach to address these needs is a text similarity method that automatically maps a curator-written statement to candidate sentences extracted from the list of referenced articles, as well as the articles in the PubMed Central database. To evaluate this proposal, we paired CDD description sentences with the top 10 matching sentences from the literature, which were given to curators for review. Through this exercise, we discovered that we were able to map the articles in the reference list to the CDD description statements with an accuracy of 77%. In the dataset that was reviewed by curators, we were able to successfully provide references for 86% of the curator statements. In addition, we suggested new articles for curator review, which were accepted by curators to be added into the reference list at an acceptance rate of 50%. Through this process, we developed a substantial corpus of similar sentences from biomedical articles on protein sequence, structure and function research, which constitute the CDD text similarity corpus. This corpus contains 5159 sentence pairs judged for their similarity on a scale from 1 (low) to 5 (high) doubly annotated by four CDD curators. Curator-assigned similarity scores have a Pearson correlation coefficient of 0.70 and an inter-annotator agreement of 85%. To date, this is the largest biomedical text similarity resource that has been manually judged, evaluated and made publicly available to the community to foster research and development of text similarity algorithms.