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.

Advancing entity recognition in biomedicine via instruction tuning of large language models.

MOTIVATION: Large Language Models (LLMs) have the potential to revolutionize the field of Natural Language Processing, excelling not only in text generation and reasoning tasks but also in their ability for zero/few-shot learning, swiftly adapting to new tasks with minimal fine-tuning. LLMs have also demonstrated great promise in biomedical and healthcare applications. However, when it comes to Named Entity Recognition (NER), particularly within the biomedical domain, LLMs fall short of the effectiveness exhibited by fine-tuned domain-specific models. One key reason is that NER is typically conceptualized as a sequence labeling task, whereas LLMs are optimized for text generation and reasoning tasks. RESULTS: We developed an instruction-based learning paradigm that transforms biomedical NER from a sequence labeling task into a generation task. This paradigm is end-to-end and streamlines the training and evaluation process by automatically repurposing pre-existing biomedical NER datasets. We further developed BioNER-LLaMA using the proposed paradigm with LLaMA-7B as the foundational LLM. We conducted extensive testing on BioNER-LLaMA across three widely recognized biomedical NER datasets, consisting of entities related to diseases, chemicals, and genes. The results revealed that BioNER-LLaMA consistently achieved higher F1-scores ranging from 5% to 30% compared to the few-shot learning capabilities of GPT-4 on datasets with different biomedical entities. We show that a general-domain LLM can match the performance of rigorously fine-tuned PubMedBERT models and PMC-LLaMA, biomedical-specific language model. Our findings underscore the potential of our proposed paradigm in developing general-domain LLMs that can rival SOTA performances in multi-task, multi-domain scenarios in biomedical and health applications. AVAILABILITY AND IMPLEMENTATION: Datasets and other resources are available at https://github.com/BIDS-Xu-Lab/BioNER-LLaMA.

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.

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.

BioREx: Improving biomedical relation extraction by leveraging heterogeneous datasets.

Biomedical relation extraction (RE) is the task of automatically identifying and characterizing relations between biomedical concepts from free text. RE is a central task in biomedical natural language processing (NLP) research and plays a critical role in many downstream applications, such as literature-based discovery and knowledge graph construction. State-of-the-art methods were used primarily to train machine learning models on individual RE datasets, such as protein-protein interaction and chemical-induced disease relation. Manual dataset annotation, however, is highly expensive and time-consuming, as it requires domain knowledge. Existing RE datasets are usually domain-specific or small, which limits the development of generalized and high-performing RE models. In this work, we present a novel framework for systematically addressing the data heterogeneity of individual datasets and combining them into a large dataset. Based on the framework and dataset, we report on BioREx, a data-centric approach for extracting relations. Our evaluation shows that BioREx achieves significantly higher performance than the benchmark system trained on the individual dataset, setting a new SOTA from 74.4% to 79.6% in F-1 measure on the recently released BioRED corpus. We further demonstrate that the combined dataset can improve performance for five different RE tasks. In addition, we show that on average BioREx compares favorably to current best-performing methods such as transfer learning and multi-task learning. Finally, we demonstrate BioREx's robustness and generalizability in two independent RE tasks not previously seen in training data: drug-drug N-ary combination and document-level gene-disease RE. The integrated dataset and optimized method have been packaged as a stand-alone tool available at https://github.com/ncbi/BioREx.

BioREx: Improving Biomedical Relation Extraction by Leveraging Heterogeneous Datasets.

Biomedical relation extraction (RE) is the task of automatically identifying and characterizing relations between biomedical concepts from free text. RE is a central task in biomedical natural language processing (NLP) research and plays a critical role in many downstream applications, such as literature-based discovery and knowledge graph construction. State-of-the-art methods were used primarily to train machine learning models on individual RE datasets, such as protein-protein interaction and chemical-induced disease relation. Manual dataset annotation, however, is highly expensive and time-consuming, as it requires domain knowledge. Existing RE datasets are usually domain-specific or small, which limits the development of generalized and high-performing RE models. In this work, we present a novel framework for systematically addressing the data heterogeneity of individual datasets and combining them into a large dataset. Based on the framework and dataset, we report on BioREx, a data-centric approach for extracting relations. Our evaluation shows that BioREx achieves significantly higher performance than the benchmark system trained on the individual dataset, setting a new SOTA from 74.4% to 79.6% in F-1 measure on the recently released BioRED corpus. We further demonstrate that the combined dataset can improve performance for five different RE tasks. In addition, we show that on average BioREx compares favorably to current best-performing methods such as transfer learning and multi-task learning. Finally, we demonstrate BioREx's robustness and generalizability in two independent RE tasks not previously seen in training data: drug-drug N-ary combination and document-level gene-disease RE. The integrated dataset and optimized method have been packaged as a stand-alone tool available at https://github.com/ncbi/BioREx.

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

MOTIVATION: 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). RESULTS: We therefore propose a novel all-in-one (AIO) scheme that uses external data from existing annotated resources to enhance the accuracy and stability of BioNER models. 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). AVAILABILITY AND IMPLEMENTATION: The source code, trained models and data for AIONER are freely available at https://github.com/ncbi/AIONER.

Bioformer: an efficient transformer language model for biomedical text mining.

Pretrained language models such as Bidirectional Encoder Representations from Transformers (BERT) have achieved state-of-the-art performance in natural language processing (NLP) tasks. Recently, BERT has been adapted to the biomedical domain. Despite the effectiveness, these models have hundreds of millions of parameters and are computationally expensive when applied to large-scale NLP applications. We hypothesized that the number of parameters of the original BERT can be dramatically reduced with minor impact on performance. In this study, we present Bioformer, a compact BERT model for biomedical text mining. We pretrained two Bioformer models (named Bioformer8L and Bioformer16L) which reduced the model size by 60% compared to BERTBase. Bioformer uses a biomedical vocabulary and was pre-trained from scratch on PubMed abstracts and PubMed Central full-text articles. We thoroughly evaluated the performance of Bioformer as well as existing biomedical BERT models including BioBERT and PubMedBERT on 15 benchmark datasets of four different biomedical NLP tasks: named entity recognition, relation extraction, question answering and document classification. The results show that with 60% fewer parameters, Bioformer16L is only 0.1% less accurate than PubMedBERT while Bioformer8L is 0.9% less accurate than PubMedBERT. Both Bioformer16L and Bioformer8L outperformed BioBERTBase-v1.1. In addition, Bioformer16L and Bioformer8L are 2-3 fold as fast as PubMedBERT/BioBERTBase-v1.1. Bioformer has been successfully deployed to PubTator Central providing gene annotations over 35 million PubMed abstracts and 5 million PubMed Central full-text articles. We make Bioformer publicly available via https://github.com/WGLab/bioformer, including pre-trained models, datasets, and instructions for downstream use.

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 2.5 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 United States. In response to the continuing evolution of the COVID-19 pandemic, this article describes significant updates to LitCovid over the last 2 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.

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.

A sequence labeling framework for extracting drug-protein relations from biomedical literature.

Automatic extracting interactions between chemical compound/drug and gene/protein are significantly beneficial to drug discovery, drug repurposing, drug design and biomedical knowledge graph construction. To promote the development of the relation extraction between drug and protein, the BioCreative VII challenge organized the DrugProt track. This paper describes the approach we developed for this task. In addition to the conventional text classification framework that has been widely used in relation extraction tasks, we propose a sequence labeling framework to drug-protein relation extraction. We first comprehensively compared the cutting-edge biomedical pre-trained language models for both frameworks. Then, we explored several ensemble methods to further improve the final performance. In the evaluation of the challenge, our best submission (i.e. the ensemble of models in two frameworks via major voting) achieved the F1-score of 0.795 on the official test set. Further, we realized the sequence labeling framework is more efficient and achieves better performance than the text classification framework. Finally, our ensemble of the sequence labeling models with majority voting achieves the best F1-score of 0.800 on the test set. DATABASE URL: https://github.com/lingluodlut/BioCreativeVII_DrugProt.

tmVar 3.0: an improved variant concept recognition and normalization tool.

MOTIVATION: 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. RESULT: We propose tmVar 3.0: an improved variant recognition and normalization system. Compared to its predecessors, tmVar 3.0 recognizes a wider spectrum of variant-related entities (e.g. allele and copy number variants), and groups together different variant mentions belonging to the same genomic sequence position in an article for improved accuracy. Moreover, tmVar 3.0 provides advanced variant normalization options such as allele-specific identifiers from the ClinGen Allele Registry. tmVar 3.0 exhibits state-of-the-art performance with over 90% in F-measure for variant recognition and normalization, when evaluated on three independent benchmarking datasets. tmVar 3.0 as well as annotations for the entire PubMed and PMC datasets are freely available for download. AVAILABILITY AND IMPLEMENTATION: https://github.com/ncbi/tmVar3.

BioRED: a rich biomedical relation extraction dataset.

Automated relation extraction (RE) from biomedical literature is critical for many downstream text mining applications in both research and real-world settings. However, most existing benchmarking datasets for biomedical RE only focus on relations of a single type (e.g. protein-protein interactions) at the sentence level, greatly limiting the development of RE systems in biomedicine. In this work, we first review commonly used named entity recognition (NER) and RE datasets. Then, we present a first-of-its-kind biomedical relation extraction dataset (BioRED) with multiple entity types (e.g. gene/protein, disease, chemical) and relation pairs (e.g. gene-disease; chemical-chemical) at the document level, on a set of 600 PubMed abstracts. Furthermore, we label each relation as describing either a novel finding or previously known background knowledge, enabling automated algorithms to differentiate between novel and background information. We assess the utility of BioRED by benchmarking several existing state-of-the-art methods, including Bidirectional Encoder Representations from Transformers (BERT)-based models, on the NER and RE tasks. Our results show that while existing approaches can reach high performance on the NER task (F-score of 89.3%), there is much room for improvement for the RE task, especially when extracting novel relations (F-score of 47.7%). Our experiments also demonstrate that such a rich dataset can successfully facilitate the development of more accurate, efficient and robust RE systems for biomedicine. Availability: The BioRED dataset and annotation guidelines are freely available at https://ftp.ncbi.nlm.nih.gov/pub/lu/BioRED/.

Artificial Intelligence in Action: Addressing the COVID-19 Pandemic with Natural Language Processing.

The COVID-19 (coronavirus disease 2019) pandemic has had a significant impact on society, both because of the serious health effects of COVID-19 and because of public health measures implemented to slow its spread. Many of these difficulties are fundamentally information needs; attempts to address these needs have caused an information overload for both researchers and the public. Natural language processing (NLP)-the branch of artificial intelligence that interprets human language-can be applied to address many of the information needs made urgent by the COVID-19 pandemic. This review surveys approximately 150 NLP studies and more than 50 systems and datasets addressing the COVID-19 pandemic. We detail work on four core NLP tasks: information retrieval, named entity recognition, literature-based discovery, and question answering. We also describe work that directly addresses aspects of the pandemic through four additional tasks: topic modeling, sentiment and emotion analysis, caseload forecasting, and misinformation detection. We conclude by discussing observable trends and remaining challenges.

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).

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.

Recent advances of automated methods for searching and extracting genomic variant information from biomedical literature.

MOTIVATION: To obtain key information for personalized medicine and cancer research, clinicians and researchers in the biomedical field are in great need of searching genomic variant information from the biomedical literature now than ever before. Due to the various written forms of genomic variants, however, it is difficult to locate the right information from the literature when using a general literature search system. To address the difficulty of locating genomic variant information from the literature, researchers have suggested various solutions based on automated literature-mining techniques. There is, however, no study for summarizing and comparing existing tools for genomic variant literature mining in terms of how to search easily for information in the literature on genomic variants. RESULTS: In this article, we systematically compared currently available genomic variant recognition and normalization tools as well as the literature search engines that adopted these literature-mining techniques. First, we explain the problems that are caused by the use of non-standard formats of genomic variants in the PubMed literature by considering examples from the literature and show the prevalence of the problem. Second, we review literature-mining tools that address the problem by recognizing and normalizing the various forms of genomic variants in the literature and systematically compare them. Third, we present and compare existing literature search engines that are designed for a genomic variant search by using the literature-mining techniques. We expect this work to be helpful for researchers who seek information about genomic variants from the literature, developers who integrate genomic variant information from the literature and beyond.

Ten tips for a text-mining-ready article: How to improve automated discoverability and interpretability.

Data-driven research in biomedical science requires structured, computable data. Increasingly, these data are created with support from automated text mining. Text-mining tools have rapidly matured: although not perfect, they now frequently provide outstanding results. We describe 10 straightforward writing tips-and a web tool, PubReCheck-guiding authors to help address the most common cases that remain difficult for text-mining tools. We anticipate these guides will help authors' work be found more readily and used more widely, ultimately increasing the impact of their work and the overall benefit to both authors and readers. PubReCheck is available at http://www.ncbi.nlm.nih.gov/research/pubrecheck.

BioConceptVec: Creating and evaluating literature-based biomedical concept embeddings on a large scale.

A massive number of biological entities, such as genes and mutations, are mentioned in the biomedical literature. The capturing of the semantic relatedness of biological entities is vital to many biological applications, such as protein-protein interaction prediction and literature-based discovery. Concept embeddings-which involve the learning of vector representations of concepts using machine learning models-have been employed to capture the semantics of concepts. To develop concept embeddings, named-entity recognition (NER) tools are first used to identify and normalize concepts from the literature, and then different machine learning models are used to train the embeddings. Despite multiple attempts, existing biomedical concept embeddings generally suffer from suboptimal NER tools, small-scale evaluation, and limited availability. In response, we employed high-performance machine learning-based NER tools for concept recognition and trained our concept embeddings, BioConceptVec, via four different machine learning models on ~30 million PubMed abstracts. BioConceptVec covers over 400,000 biomedical concepts mentioned in the literature and is of the largest among the publicly available biomedical concept embeddings to date. To evaluate the validity and utility of BioConceptVec, we respectively performed two intrinsic evaluations (identifying related concepts based on drug-gene and gene-gene interactions) and two extrinsic evaluations (protein-protein interaction prediction and drug-drug interaction extraction), collectively using over 25 million instances from nine independent datasets (17 million instances from six intrinsic evaluation tasks and 8 million instances from three extrinsic evaluation tasks), which is, by far, the most comprehensive to our best knowledge. The intrinsic evaluation results demonstrate that BioConceptVec consistently has, by a large margin, better performance than existing concept embeddings in identifying similar and related concepts. More importantly, the extrinsic evaluation results demonstrate that using BioConceptVec with advanced deep learning models can significantly improve performance in downstream bioinformatics studies and biomedical text-mining applications. Our BioConceptVec embeddings and benchmarking datasets are publicly available at https://github.com/ncbi-nlp/BioConceptVec.