This paper evaluates the retrieval effectiveness of relevance ranking strategies on a collection of 55 queries and about 160,000 MEDLINE((R)) citations used in the 2006 and 2007 Text Retrieval Conference (TREC) Genomics Tracks. The authors study two relevance ranking strategies: term frequency-inverse document frequency (TF-IDF) weighting and sentence-level co-occurrence, and examine their ability to rank retrieved MEDLINE documents given user queries. Furthermore, the authors use the reverse chronological order-PubMed's default display option-as a baseline for comparison. Retrieval effectiveness is assessed using both mean average precision and mean rank precision. Experimental results show that retrievals based on the two strategies had improved performance over the baseline performance, and that TF-IDF weighting is more effective in retrieving relevant documents based on the comparison between the two strategies.

In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, Reference Sequence, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus, Entrez Probe, GENSAT, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool, Biosystems, Peptidome, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. All these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

Biomedical research yields vast information, much of which is only accessible through the literature. Consequently, literature search is crucial for healthcare and biomedicine. Recent improvements in artificial intelligence (AI) have expanded functionality beyond keywords, but they might be unfamiliar to clinicians and researchers. In response, we present an overview of over 30 literature search tools tailored to common biomedical use cases, aiming at helping readers efficiently fulfill their information needs. We first discuss recent improvements and continued challenges of the widely used PubMed. Then, we describe AI-based literature search tools catering to five specific information needs: 1. Evidence-based medicine. 2. Precision medicine and genomics. 3. Searching by meaning, including questions. 4. Finding related articles with literature recommendation. 5. Discovering hidden associations through literature mining. Finally, we discuss the impacts of recent developments of large language models such as ChatGPT on biomedical information seeking.

Determining usefulness of biomedical text mining systems requires realistic task definition and data selection criteria without artificial constraints, measuring performance aspects that go beyond traditional metrics. The BioCreative III Protein-Protein Interaction (PPI) tasks were motivated by such considerations, trying to address aspects including how the end user would oversee the generated output, for instance by providing ranked results, textual evidence for human interpretation or measuring time savings by using automated systems. Detecting articles describing complex biological events like PPIs was addressed in the Article Classification Task (ACT), where participants were asked to implement tools for detecting PPI-describing abstracts. Therefore the BCIII-ACT corpus was provided, which includes a training, development and test set of over 12,000 PPI relevant and non-relevant PubMed abstracts labeled manually by domain experts and recording also the human classification times. The Interaction Method Task (IMT) went beyond abstracts and required mining for associations between more than 3,500 full text articles and interaction detection method ontology concepts that had been applied to detect the PPIs reported in them.

In addition to maintaining the GenBank® nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI Website. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Genome and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, BioProject, BioSample, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Probe, Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), Biosystems, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

As suggested in recent studies, species recognition and disambiguation is one of the most critical and challenging steps in many downstream text-mining applications such as the gene normalization task and protein-protein interaction extraction. We report SR4GN: an open source tool for species recognition and disambiguation in biomedical text. In addition to the species detection function in existing tools, SR4GN is optimized for the Gene Normalization task. As such it is developed to link detected species with corresponding gene mentions in a document. SR4GN achieves 85.42% in accuracy and compares favorably to the other state-of-the-art techniques in benchmark experiments. Finally, SR4GN is implemented as a standalone software tool, thus making it convenient and robust for use in many text-mining applications. SR4GN can be downloaded at: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/downloads/SR4GN.

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.

Early menopause and infertility often occur in female cancer patients after chemotherapy (CTx). For these patients, oocyte/embryo cryopreservation or ovarian tissue cryopreservation is the current modality for fertility preservation. However, the above methods are limited in the long-term protection of ovarian function, especially for fertility preservation (very few females with cancer have achieved pregnancy with cryopreserved ovarian tissue or eggs until now). In addition, the above methods are subject to their scope (females with no husband or prepubertal females with no mature oocytes). Thus, many females who suffer from cancers would not adopt the above methods pre- and post-CTx due to their uncertainty, safety and cost-effectiveness. Therefore, millions of women have achieved long-term survival after thorough CTx treatment and have desired to rescue their ovarian function and fertility with economic, durable and reliable methods. Recently, some studies showed that mice with infertility caused by CTx can produce normal offspring through intraovarian injection of exogenous female germline stem cells (FGSCs). Though exogenous FGSC can be derived from mice without immune rejection in the same strain, it is difficult to obtain human female germline stem cells (hFGSCs), and immune rejection could occur between different individuals. In this study, infertility in mice was caused by CTx, and the ability of FGSCs to restore ovarian function or even produce offspring was assessed. We had successfully isolated and purified the FGSCs from adult female mice two weeks after CTx. After infection with GFP-carrying virus, the FGSCs were transplanted into ovaries of mice with infertility caused by CTx. Finally, ovarian function was restored and the recipients produced offspring long-term. These findings showed that mice with CTx possessed FGSCs, restoring ovarian function and avoiding immune rejection from exogenous germline stem cells.

Gene function curation via Gene Ontology (GO) annotation is a common task among Model Organism Database groups. Owing to its manual nature, this task is considered one of the bottlenecks in literature curation. There have been many previous attempts at automatic identification of GO terms and supporting information from full text. However, few systems have delivered an accuracy that is comparable with humans. One recognized challenge in developing such systems is the lack of marked sentence-level evidence text that provides the basis for making GO annotations. We aim to create a corpus that includes the GO evidence text along with the three core elements of GO annotations: (i) a gene or gene product, (ii) a GO term and (iii) a GO evidence code. To ensure our results are consistent with real-life GO data, we recruited eight professional GO curators and asked them to follow their routine GO annotation protocols. Our annotators marked up more than 5000 text passages in 200 articles for 1356 distinct GO terms. For evidence sentence selection, the inter-annotator agreement (IAA) results are 9.3% (strict) and 42.7% (relaxed) in F1-measures. For GO term selection, the IAAs are 47% (strict) and 62.9% (hierarchical). Our corpus analysis further shows that abstracts contain ∼ 10% of relevant evidence sentences and 30% distinct GO terms, while the Results/Experiment section has nearly 60% relevant sentences and >70% GO terms. Further, of those evidence sentences found in abstracts, less than one-third contain enough experimental detail to fulfill the three core criteria of a GO annotation. This result demonstrates the need of using full-text articles for text mining GO annotations. Through its use at the BioCreative IV GO (BC4GO) task, we expect our corpus to become a valuable resource for the BioNLP research community. Database URL: http://www.biocreative.org/resources/corpora/bc-iv-go-task-corpus/.

Gene ontology (GO) annotation is a common task among model organism databases (MODs) for capturing gene function data from journal articles. It is a time-consuming and labor-intensive task, and is thus often considered as one of the bottlenecks in literature curation. There is a growing need for semiautomated or fully automated GO curation techniques that will help database curators to rapidly and accurately identify gene function information in full-length articles. Despite multiple attempts in the past, few studies have proven to be useful with regard to assisting real-world GO curation. The shortage of sentence-level training data and opportunities for interaction between text-mining developers and GO curators has limited the advances in algorithm development and corresponding use in practical circumstances. To this end, we organized a text-mining challenge task for literature-based GO annotation in BioCreative IV. More specifically, we developed two subtasks: (i) to automatically locate text passages that contain GO-relevant information (a text retrieval task) and (ii) to automatically identify relevant GO terms for the genes in a given article (a concept-recognition task). With the support from five MODs, we provided teams with >4000 unique text passages that served as the basis for each GO annotation in our task data. Such evidence text information has long been recognized as critical for text-mining algorithm development but was never made available because of the high cost of curation. In total, seven teams participated in the challenge task. From the team results, we conclude that the state of the art in automatically mining GO terms from literature has improved over the past decade while much progress is still needed for computer-assisted GO curation. Future work should focus on addressing remaining technical challenges for improved performance of automatic GO concept recognition and incorporating practical benefits of text-mining tools into real-world GO annotation.

The goal of the gene normalization task is to link genes or gene products mentioned in the literature to biological databases. This is a key step in an accurate search of the biological literature. It is a challenging task, even for the human expert; genes are often described rather than referred to by gene symbol and, confusingly, one gene name may refer to different genes (often from different organisms). For BioCreative II, the task was to list the Entrez Gene identifiers for human genes or gene products mentioned in PubMed/MEDLINE abstracts. We selected abstracts associated with articles previously curated for human genes. We provided 281 expert-annotated abstracts containing 684 gene identifiers for training, and a blind test set of 262 documents containing 785 identifiers, with a gold standard created by expert annotators. Inter-annotator agreement was measured at over 90%.

Over the last 25 years, biology has entered the genomic era and is becoming a science of 'big data'. Most interpretations of genomic analyses rely on accurate functional annotations of the proteins encoded by more than 500 000 genomes sequenced to date. By different estimates, only half the predicted sequenced proteins carry an accurate functional annotation, and this percentage varies drastically between different organismal lineages. Such a large gap in knowledge hampers all aspects of biological enterprise and, thereby, is standing in the way of genomic biology reaching its full potential. A brainstorming meeting to address this issue funded by the National Science Foundation was held during 3-4 February 2022. Bringing together data scientists, biocurators, computational biologists and experimentalists within the same venue allowed for a comprehensive assessment of the current state of functional annotations of protein families. Further, major issues that were obstructing the field were identified and discussed, which ultimately allowed for the proposal of solutions on how to move forward.

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.

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/.

As one of the most ubiquitous diagnostic imaging tests in medical practice, chest radiography requires timely reporting of potential findings and diagnosis of diseases in the images. Automated, fast, and reliable detection of diseases based on chest radiography is a critical step in radiology workflow. In this work, we developed and evaluated various deep convolutional neural networks (CNN) for differentiating between normal and abnormal frontal chest radiographs, in order to help alert radiologists and clinicians of potential abnormal findings as a means of work list triaging and reporting prioritization. A CNN-based model achieved an AUC of 0.9824 ± 0.0043 (with an accuracy of 94.64 ± 0.45%, a sensitivity of 96.50 ± 0.36% and a specificity of 92.86 ± 0.48%) for normal versus abnormal chest radiograph classification. The CNN model obtained an AUC of 0.9804 ± 0.0032 (with an accuracy of 94.71 ± 0.32%, a sensitivity of 92.20 ± 0.34% and a specificity of 96.34 ± 0.31%) for normal versus lung opacity classification. Classification performance on the external dataset showed that the CNN model is likely to be highly generalizable, with an AUC of 0.9444 ± 0.0029. The CNN model pre-trained on cohorts of adult patients and fine-tuned on pediatric patients achieved an AUC of 0.9851 ± 0.0046 for normal versus pneumonia classification. Pretraining with natural images demonstrates benefit for a moderate-sized training image set of about 8500 images. The remarkable performance in diagnostic accuracy observed in this study shows that deep CNNs can accurately and effectively differentiate normal and abnormal chest radiographs, thereby providing potential benefits to radiology workflow and patient care.

Chemotherapy-induced ovarian aging not only increases the risk for early menopause-related complications but also results in infertility in young female cancer survivors. Oogonial stem cells have the ability to generate new oocytes and thus provide new opportunities for treating ovarian aging and female infertility. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phenol derived from plants, that has been shown to have positive effects on longevity and redox flow in lipid metabolism and a preventive function against certain tumors. To evaluate whether resveratrol could promote the repair of oogonial stem cells damage in a busulfan/cyclophosphamide (Bu/Cy)-induced accelerated ovarian aging model, female mice were administered 30 and 100 mg/kg/d resveratrol through a gavage for 2 weeks. We demonstrated that resveratrol (30 mg/kg/d) relieved oogonial stem cells loss and showed an attenuating effect on Bu/Cy-induced oxidative apoptosis in mouse ovaries, which may be attributed to the attenuation of oxidative levels in ovaries. Additionally, we also showed that Res exerted a dose-dependent effect on oogonial stem cells and attenuated H2O2-induced cytotoxicity and oxidative stress injury by activating Nrf2 in vitro. Therefore, resveratrol could be of a potential therapeutic drug used to prevent chemotherapy-induced ovarian aging.

Distributed word representations have become an essential foundation for biomedical natural language processing (BioNLP), text mining and information retrieval. Word embeddings are traditionally computed at the word level from a large corpus of unlabeled text, ignoring the information present in the internal structure of words or any information available in domain specific structured resources such as ontologies. However, such information holds potentials for greatly improving the quality of the word representation, as suggested in some recent studies in the general domain. Here we present BioWordVec: an open set of biomedical word vectors/embeddings that combines subword information from unlabeled biomedical text with a widely-used biomedical controlled vocabulary called Medical Subject Headings (MeSH). We assess both the validity and utility of our generated word embeddings over multiple NLP tasks in the biomedical domain. Our benchmarking results demonstrate that our word embeddings can result in significantly improved performance over the previous state of the art in those challenging tasks.

Understanding the drivers of research on human genes is a critical component to success of translation efforts of genomics into medicine and public health. Using publicly available curated online databases we sought to identify specific genes that are featured in translational genetic research in comparison to all genomics research publications. Articles in the CDC's Public Health Genomics and Precision Health Knowledge Base were stratified into studies that have moved beyond basic research to population and clinical epidemiologic studies (T1: clinical and population human genome epidemiology research), and studies that evaluate, implement, and assess impact of genes in clinical and public health areas (T2+: beyond bench to bedside). We examined gene counts and numbers of publications within these phases of translation in comparison to all genes from Medline. We are able to highlight those genes that are moving from basic research to clinical and public health translational research, namely in cancer and a few genetic diseases with high penetrance and clinical actionability. Identifying human genes of translational value is an important step towards determining an evidence-based trajectory of the human genome in clinical and public health practice over time.

Due to the importance of identifying relations between chemicals and diseases for new drug discovery and improving chemical safety, there has been a growing interest in developing automatic relation extraction systems for capturing these relations from the rich and rapid-growing biomedical literature. In this work we aim to build on current advances in named entity recognition and a recent BioCreative effort to further improve the state of the art in biomedical relation extraction, in particular for the chemical-induced disease (CID) relations.

Biological knowledgebases, such as UniProtKB/Swiss-Prot, constitute an essential component of daily scientific research by offering distilled, summarized and computable knowledge extracted from the literature by expert curators. While knowledgebases play an increasingly important role in the scientific community, their ability to keep up with the growth of biomedical literature is under scrutiny. Using UniProtKB/Swiss-Prot as a case study, we address this concern via multiple literature triage approaches.