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.

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.

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).

MOTIVATION: Interest in text mining full-text biomedical research articles is growing. To facilitate automated processing of nearly 3 million full-text articles (in PubMed Central® Open Access and Author Manuscript subsets) and to improve interoperability, we convert these articles to BioC, a community-driven simple data structure in either XML or JavaScript Object Notation format for conveniently sharing text and annotations. RESULTS: The resultant articles can be downloaded via both File Transfer Protocol for bulk access and a Web API for updates or a more focused collection. Since the availability of the Web API in 2017, our BioC collection has been widely used by the research community. AVAILABILITY AND IMPLEMENTATION: https://www.ncbi.nlm.nih.gov/research/bionlp/APIs/BioC-PMC/.

Log analysis shows that PubMed users frequently use author names in queries for retrieving scientific literature. However, author name ambiguity may lead to irrelevant retrieval results. To improve the PubMed user experience with author name queries, we designed an author name disambiguation system consisting of similarity estimation and agglomerative clustering. A machine-learning method was employed to score the features for disambiguating a pair of papers with ambiguous names. These features enable the computation of pairwise similarity scores to estimate the probability of a pair of papers belonging to the same author, which drives an agglomerative clustering algorithm regulated by 2 factors: name compatibility and probability level. With transitivity violation correction, high precision author clustering is achieved by focusing on minimizing false-positive pairing. Disambiguation performance is evaluated with manual verification of random samples of pairs from clustering results. When compared with a state-of-the-art system, our evaluation shows that among all the pairs the lumping error rate drops from 10.1% to 2.2% for our system, while the splitting error rises from 1.8% to 7.7%. This results in an overall error rate of 9.9%, compared with 11.9% for the state-of-the-art method. Other evaluations based on gold standard data also show the increase in accuracy of our clustering. We attribute the performance improvement to the machine-learning method driven by a large-scale training set and the clustering algorithm regulated by a name compatibility scheme preferring precision. With integration of the author name disambiguation system into the PubMed search engine, the overall click-through-rate of PubMed users on author name query results improved from 34.9% to 36.9%.

Information encoded in natural language in biomedical literature publications is only useful if efficient and reliable ways of accessing and analyzing that information are available. Natural language processing and text mining tools are therefore essential for extracting valuable information, however, the development of powerful, highly effective tools to automatically detect central biomedical concepts such as diseases is conditional on the availability of annotated corpora. This paper presents the disease name and concept annotations of the NCBI disease corpus, a collection of 793 PubMed abstracts fully annotated at the mention and concept level to serve as a research resource for the biomedical natural language processing community. Each PubMed abstract was manually annotated by two annotators with disease mentions and their corresponding concepts in Medical Subject Headings (MeSH®) or Online Mendelian Inheritance in Man (OMIM®). Manual curation was performed using PubTator, which allowed the use of pre-annotations as a pre-step to manual annotations. Fourteen annotators were randomly paired and differing annotations were discussed for reaching a consensus in two annotation phases. In this setting, a high inter-annotator agreement was observed. Finally, all results were checked against annotations of the rest of the corpus to assure corpus-wide consistency. The public release of the NCBI disease corpus contains 6892 disease mentions, which are mapped to 790 unique disease concepts. Of these, 88% link to a MeSH identifier, while the rest contain an OMIM identifier. We were able to link 91% of the mentions to a single disease concept, while the rest are described as a combination of concepts. In order to help researchers use the corpus to design and test disease identification methods, we have prepared the corpus as training, testing and development sets. To demonstrate its utility, we conducted a benchmarking experiment where we compared three different knowledge-based disease normalization methods with a best performance in F-measure of 63.7%. These results show that the NCBI disease corpus has the potential to significantly improve the state-of-the-art in disease name recognition and normalization research, by providing a high-quality gold standard thus enabling the development of machine-learning based approaches for such tasks. The NCBI disease corpus, guidelines and other associated resources are available at: http://www.ncbi.nlm.nih.gov/CBBresearch/Dogan/DISEASE/.

MOTIVATION: Despite the central role of diseases in biomedical research, there have been much fewer attempts to automatically determine which diseases are mentioned in a text-the task of disease name normalization (DNorm)-compared with other normalization tasks in biomedical text mining research. METHODS: In this article we introduce the first machine learning approach for DNorm, using the NCBI disease corpus and the MEDIC vocabulary, which combines MeSH® and OMIM. Our method is a high-performing and mathematically principled framework for learning similarities between mentions and concept names directly from training data. The technique is based on pairwise learning to rank, which has not previously been applied to the normalization task but has proven successful in large optimization problems for information retrieval. RESULTS: We compare our method with several techniques based on lexical normalization and matching, MetaMap and Lucene. Our algorithm achieves 0.782 micro-averaged F-measure and 0.809 macro-averaged F-measure, an increase over the highest performing baseline method of 0.121 and 0.098, respectively. AVAILABILITY: The source code for DNorm is available at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/DNorm, along with a web-based demonstration and links to the NCBI disease corpus. Results on PubMed abstracts are available in PubTator: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/PubTator .

Associating functional information with biological sequences remains a challenge for machine learning methods. The performance of these methods often depends on deriving predictive features from the sequences sought to be classified. Feature generation is a difficult problem, as the connection between the sequence features and the sought property is not known a priori. It is often the task of domain experts or exhaustive feature enumeration techniques to generate a few features whose predictive power is then tested in the context of classification. This paper proposes an evolutionary algorithm to effectively explore a large feature space and generate predictive features from sequence data. The effectiveness of the algorithm is demonstrated on an important component of the gene-finding problem, DNA splice site prediction. This application is chosen due to the complexity of the features needed to obtain high classification accuracy and precision. Our results test the effectiveness of the obtained features in the context of classification by Support Vector Machines and show significant improvement in accuracy and precision over state-of-the-art approaches.

BACKGROUND: Patient records contain valuable information regarding explanation of diagnosis, progression of disease, prescription and/or effectiveness of treatment, and more. Automatic recognition of clinically important concepts and the identification of relationships between those concepts in patient records are preliminary steps for many important applications in medical informatics, ranging from quality of care to hypothesis generation. METHODS: In this work we describe an approach that facilitates the automatic recognition of eight relationships defined between medical problems, treatments and tests. Unlike the traditional bag-of-words representation, in this work, we represent a relationship with a scheme of five distinct context-blocks determined by the position of concepts in the text. As a preliminary step to relationship recognition, and in order to provide an end-to-end system, we also addressed the automatic extraction of medical problems, treatments and tests. Our approach combined the outcome of a statistical model for concept recognition and simple natural language processing features in a conditional random fields model. A set of 826 patient records from the 4th i2b2 challenge was used for training and evaluating the system. RESULTS: Results show that our concept recognition system achieved an F-measure of 0.870 for exact span concept detection. Moreover the context-block representation of relationships was more successful (F-Measure = 0.775) at identifying relationships than bag-of-words (F-Measure = 0.402). Most importantly, the performance of the end-to-end system of relationship extraction using automatically extracted concepts (F-Measure = 0.704) was comparable to that obtained using manually annotated concepts (F-Measure = 0.711), and their difference was not statistically significant. CONCLUSIONS: We extracted important clinical relationships from text in an automated manner, starting with concept recognition, and ending with relationship identification. The advantage of the context-blocks representation scheme was the correct management of word position information, which may be critical in identifying certain relationships. Our results may serve as benchmark for comparison to other systems developed on i2b2 challenge data. Finally, our system may serve as a preliminary step for other discovery tasks in medical informatics.

Life science researchers and health care professionals rely heavily on biomedical literature databases such as MEDLINE to access information essential for research, health care, education, as well as to keep up with the latest developments in their fields. Providing ways to efficiently access and analyze text information is critical and is becoming more challenging with the increasing volume of publications in the biomedical domain. The last decade has shown an exponential rate of growth of biomedical literature [ 1 ].

The identification of relationships between clinical concepts in patient records is a preliminary step for many important applications in medical informatics, ranging from quality of care to hypothesis generation. In this work we describe an approach that facilitates the automatic recognition of relationships defined between two different concepts in text. Unlike the traditional bag-of-words representation, in this work, a relationship is represented with a scheme of five distinct context-blocks based on the position of concepts in the text. This scheme was applied to eight different relationships, between medical problems, treatments and tests, on a set of 349 patient records from the 4th i2b2 challenge. Results show that the context-block representation was very successful (F-Measure = 0.775) compared to the bag-of-words model (F-Measure = 0.402). The advantage of this representation scheme was the correct management of word position information, which may be critical in identifying certain relationships.

MOTIVATION: Recognizing words that are key to a document is important for ranking relevant scientific documents. Traditionally, important words in a document are either nominated subjectively by authors and indexers or selected objectively by some statistical measures. As an alternative, we propose to use documents' words popularity in user queries to identify click-words, a set of prominent words from the users' perspective. Although they often overlap, click-words differ significantly from other document keywords. RESULTS: We developed a machine learning approach to learn the unique characteristics of click-words. Each word was represented by a set of features that included different types of information, such as semantic type, part of speech tag, term frequency-inverse document frequency (TF-IDF) weight and location in the abstract. We identified the most important features and evaluated our model using 6 months of PubMed click-through logs. Our results suggest that, in addition to carrying high TF-IDF weight, click-words tend to be biomedical entities, to exist in article titles, and to occur repeatedly in article abstracts. Given the abstract and title of a document, we are able to accurately predict the words likely to appear in user queries that lead to document clicks.

OBJECTIVE: The authors used the i2b2 Medication Extraction Challenge to evaluate their entity extraction methods, contribute to the generation of a publicly available collection of annotated clinical notes, and start developing methods for ontology-based reasoning using structured information generated from the unstructured clinical narrative. DESIGN: Extraction of salient features of medication orders from the text of de-identified hospital discharge summaries was addressed with a knowledge-based approach using simple rules and lookup lists. The entity recognition tool, MetaMap, was combined with dose, frequency, and duration modules specifically developed for the Challenge as well as a prototype module for reason identification. MEASUREMENTS: Evaluation metrics and corresponding results were provided by the Challenge organizers. RESULTS: The results indicate that robust rule-based tools achieve satisfactory results in extraction of simple elements of medication orders, but more sophisticated methods are needed for identification of reasons for the orders and durations. LIMITATIONS: Owing to the time constraints and nature of the Challenge, some obvious follow-on analysis has not been completed yet. CONCLUSIONS: The authors plan to integrate the new modules with MetaMap to enhance its accuracy. This integration effort will provide guidance in retargeting existing tools for better processing of clinical text.

BACKGROUND: Accurate selection of splice sites during the splicing of precursors to messenger RNA requires both relatively well-characterized signals at the splice sites and auxiliary signals in the adjacent exons and introns. We previously described a feature generation algorithm (FGA) that is capable of achieving high classification accuracy on human 3' splice sites. In this paper, we extend the splice-site prediction to 5' splice sites and explore the generated features for biologically meaningful splicing signals. RESULTS: We present examples from the observed features that correspond to known signals, both core signals (including the branch site and pyrimidine tract) and auxiliary signals (including GGG triplets and exon splicing enhancers). We present evidence that features identified by FGA include splicing signals not found by other methods. CONCLUSION: Our generated features capture known biological signals in the expected sequence interval flanking splice sites. The method can be easily applied to other species and to similar classification problems, such as tissue-specific regulatory elements, polyadenylation sites, promoters, etc.