SUMMARY: Biological relation networks contain rich information for understanding the biological mechanisms behind the relationship of entities such as genes, proteins, diseases, and chemicals. The vast growth of biomedical literature poses significant challenges in updating the network knowledge. The recent Biomedical Relation Extraction Dataset (BioRED) provides valuable manual annotations, facilitating the development of machine learning and pre-trained language model approaches for automatically identifying novel document-level (inter-sentence context) relationships. Nonetheless, its annotations lack directionality (subject/object) for the entity roles, which is essential for studying complex biological networks. Herein, we annotate the entity roles of the relationships in the BioRED corpus and subsequently propose a novel multi-task language model with soft-prompt learning to jointly identify the relationship, novel findings, and entity roles. Our results include an enriched BioRED corpus with 10 864 directionality annotations. Moreover, our proposed method outperforms existing large language models, such as the state-of-the-art GPT-4 and Llama-3, on two benchmarking tasks. AVAILABILITY AND IMPLEMENTATION: Our source code and dataset are available at https://github.com/ncbi-nlp/BioREDirect.

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: 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.

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.

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/.

The study aims at developing a neural network model to improve the performance of Human Phenotype Ontology (HPO) concept recognition tools. We used the terms, definitions, and comments about the phenotypic concepts in the HPO database to train our model. The document to be analyzed is first split into sentences and annotated with a base method to generate candidate concepts. The sentences, along with the candidate concepts, are then fed into the pre-trained model for re-ranking. Our model comprises the pre-trained BlueBERT and a feature selection module, followed by a contrastive loss. We re-ranked the results generated by three robust HPO annotation tools and compared the performance against most of the existing approaches. The experimental results show that our model can improve the performance of the existing methods. Significantly, it boosted 3.0% and 5.6% in F1 score on the two evaluated datasets compared with the base methods. It removed more than 80% of the false positives predicted by the base methods, resulting in up to 18% improvement in precision. Our model utilizes the descriptive data in the ontology and the contextual information in the sentences for re-ranking. The results indicate that the additional information and the re-ranking model can significantly enhance the precision of HPO concept recognition compared with the base method.

MOTIVATION: A biomedical relation statement is commonly expressed in multiple sentences and consists of many concepts, including gene, disease, chemical and mutation. To automatically extract information from biomedical literature, existing biomedical text-mining approaches typically formulate the problem as a cross-sentence n-ary relation-extraction task that detects relations among n entities across multiple sentences, and use either a graph neural network (GNN) with long short-term memory (LSTM) or an attention mechanism. Recently, Transformer has been shown to outperform LSTM on many natural language processing (NLP) tasks. RESULTS: In this work, we propose a novel architecture that combines Bidirectional Encoder Representations from Transformers with Graph Transformer (BERT-GT), through integrating a neighbor-attention mechanism into the BERT architecture. Unlike the original Transformer architecture, which utilizes the whole sentence(s) to calculate the attention of the current token, the neighbor-attention mechanism in our method calculates its attention utilizing only its neighbor tokens. Thus, each token can pay attention to its neighbor information with little noise. We show that this is critically important when the text is very long, as in cross-sentence or abstract-level relation-extraction tasks. Our benchmarking results show improvements of 5.44% and 3.89% in accuracy and F1-measure over the state-of-the-art on n-ary and chemical-protein relation datasets, suggesting BERT-GT is a robust approach that is applicable to other biomedical relation extraction tasks or datasets. AVAILABILITY AND IMPLEMENTATION: the source code of BERT-GT will be made freely available at https://github.com/ncbi/bert_gt upon publication. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Automatic phenotype concept recognition from unstructured text remains a challenging task in biomedical text mining research. Previous works that address the task typically use dictionary-based matching methods, which can achieve high precision but suffer from lower recall. Recently, machine learning-based methods have been proposed to identify biomedical concepts, which can recognize more unseen concept synonyms by automatic feature learning. However, most methods require large corpora of manually annotated data for model training, which is difficult to obtain due to the high cost of human annotation. RESULTS: In this article, we propose PhenoTagger, a hybrid method that combines both dictionary and machine learning-based methods to recognize Human Phenotype Ontology (HPO) concepts in unstructured biomedical text. We first use all concepts and synonyms in HPO to construct a dictionary, which is then used to automatically build a distantly supervised training dataset for machine learning. Next, a cutting-edge deep learning model is trained to classify each candidate phrase (n-gram from input sentence) into a corresponding concept label. Finally, the dictionary and machine learning-based prediction results are combined for improved performance. Our method is validated with two HPO corpora, and the results show that PhenoTagger compares favorably to previous methods. In addition, to demonstrate the generalizability of our method, we retrained PhenoTagger using the disease ontology MEDIC for disease concept recognition to investigate the effect of training on different ontologies. Experimental results on the NCBI disease corpus show that PhenoTagger without requiring manually annotated training data achieves competitive performance as compared with state-of-the-art supervised methods. AVAILABILITYAND IMPLEMENTATION: The source code, API information and data for PhenoTagger are freely available at https://github.com/ncbi-nlp/PhenoTagger. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Bio-MEMS (micro-electromechanical systems) are the major field of the biomedical chips. Many Bio-MEMS chips are worked in the water-related systems. So far except for the general chip probing (dry test), the latter testing can't be able under the mass-production testing. The testing coverage in the Bio-MEMS and the ISFET (ion-sensitive field-effect transistor) still stays low and eventually lead to the low yield of the end product. This present situation is not able to meet the market mass-production requirement. Moreover, some chips like ISFET chips even are needed to immerse in solution during the process. However, the immersed testing systems are difficult to apply to mass production. Therefore, we had developed a validated novel dispensed method which was easier to be introduced to mass production. In the experiment of chip sensitivity, the testing results from both of the novel dispensed method and the immersed method showed the high accuracy and precision. The possible contamination of the novel dispensed method was further examined. The results showed that there were no effects during every testing process in this novel dispensed method. Besides, this novel dispensed method can be applied to the ISFET with different ions (H+, Na+ and K+), even the ISFET from the different companies. As above-mentioned, these experimental results showed the novel dispensed method can be available and potential on testing. And this method can be applied to most of the biomedical chips in the phase of foundry test.

Natural language processing (NLP) is widely applied in biological domains to retrieve information from publications. Systems to address numerous applications exist, such as biomedical named entity recognition (BNER), named entity normalization (NEN) and protein-protein interaction extraction (PPIE). High-quality datasets can assist the development of robust and reliable systems; however, due to the endless applications and evolving techniques, the annotations of benchmark datasets may become outdated and inappropriate. In this study, we first review commonlyused BNER datasets and their potential annotation problems such as inconsistency and low portability. Then, we introduce a revised version of the JNLPBA dataset that solves potential problems in the original and use state-of-the-art named entity recognition systems to evaluate its portability to different kinds of biomedical literature, including protein-protein interaction and biology events. Lastly, we introduce an ensembled biomedical entity dataset (EBED) by extending the revised JNLPBA dataset with PubMed Central full-text paragraphs, figure captions and patent abstracts. This EBED is a multi-task dataset that covers annotations including gene, disease and chemical entities. In total, it contains 85000 entity mentions, 25000 entity mentions with database identifiers and 5000 attribute tags. To demonstrate the usage of the EBED, we review the BNER track from the AI CUP Biomedical Paper Analysis challenge. Availability: The revised JNLPBA dataset is available at https://iasl-btm.iis.sinica.edu.tw/BNER/Content/Re vised_JNLPBA.zip. The EBED dataset is available at https://iasl-btm.iis.sinica.edu.tw/BNER/Content/AICUP _EBED_dataset.rar. Contact: Email: [email protected], Tel. 886-3-4227151 ext. 35203, Fax: 886-3-422-2681 Email: [email protected], Tel. 886-2-2788-3799 ext. 2211, Fax: 886-2-2782-4814 Supplementary information: Supplementary data are available at Briefings in Bioinformatics online.

BACKGROUND: Biomedical semantic role labeling (BioSRL) is a natural language processing technique that identifies the semantic roles of the words or phrases in sentences describing biological processes and expresses them as predicate-argument structures (PAS's). Currently, a major problem of BioSRL is that most systems label every node in a full parse tree independently; however, some nodes always exhibit dependency. In general SRL, collective approaches based on the Markov logic network (MLN) model have been successful in dealing with this problem. However, in BioSRL such an approach has not been attempted because it would require more training data to recognize the more specialized and diverse terms found in biomedical literature, increasing training time and computational complexity. RESULTS: We first constructed a collective BioSRL system based on MLN. This system, called collective BIOSMILE (CBIOSMILE), is trained on the BioProp corpus. To reduce the resources used in BioSRL training, we employ a tree-pruning filter to remove unlikely nodes from the parse tree and four argument candidate identifiers to retain candidate nodes in the tree. Nodes not recognized by any candidate identifier are discarded. The pruned annotated parse trees are used to train a resource-saving MLN-based system, which is referred to as resource-saving collective BIOSMILE (RCBIOSMILE). Our experimental results show that our proposed CBIOSMILE system outperforms BIOSMILE, which is the top BioSRL system. Furthermore, our proposed RCBIOSMILE maintains the same level of accuracy as CBIOSMILE using 92% less memory and 57% less training time. CONCLUSIONS: This greatly improved efficiency makes RCBIOSMILE potentially suitable for training on much larger BioSRL corpora over more biomedical domains. Compared to real-world biomedical corpora, BioProp is relatively small, containing only 445 MEDLINE abstracts and 30 event triggers. It is not large enough for practical applications, such as pathway construction. We consider it of primary importance to pursue SRL training on large corpora in the future.

OBJECTIVE: Patient discharge summaries provide detailed medical information about hospitalized patients and are a rich resource of data for clinical record text mining. The textual expressions of this information are highly variable. In order to acquire a precise understanding of the patient, it is important to uncover the relationship between all instances in the text. In natural language processing (NLP), this task falls under the category of coreference resolution. DESIGN: A key contribution of this paper is the application of contextual-dependent rules that describe relationships between coreference pairs. To resolve phrases that refer to the same entity, the authors use these rules in three representative NLP systems: one rule-based, another based on the maximum entropy model, and the last a system built on the Markov logic network (MLN) model. RESULTS: The experimental results show that the proposed MLN-based system outperforms the baseline system (exact match) by average F-scores of 4.3% and 5.7% on the Beth and Partners datasets, respectively. Finally, the three systems were integrated into an ensemble system, further improving performance to 87.21%, which is 4.5% more than the official i2b2 Track 1C average (82.7%). CONCLUSION: In this paper, the main challenges in the resolution of coreference relations in patient discharge summaries are described. Several rules are proposed to exploit contextual information, and three approaches presented. While single systems provided promising results, an ensemble approach combining the three systems produced a better performance than even the best single system.

BACKGROUND: DNA methylation is regarded as a potential biomarker in the diagnosis and treatment of cancer. The relations between aberrant gene methylation and cancer development have been identified by a number of recent scientific studies. In a previous work, we used co-occurrences to mine those associations and compiled the MeInfoText 1.0 database. To reduce the amount of manual curation and improve the accuracy of relation extraction, we have now developed MeInfoText 2.0, which uses a machine learning-based approach to extract gene methylation-cancer relations. DESCRIPTION: Two maximum entropy models are trained to predict if aberrant gene methylation is related to any type of cancer mentioned in the literature. After evaluation based on 10-fold cross-validation, the average precision/recall rates of the two models are 94.7/90.1 and 91.8/90% respectively. MeInfoText 2.0 provides the gene methylation profiles of different types of human cancer. The extracted relations with maximum probability, evidence sentences, and specific gene information are also retrievable. The database is available at http://bws.iis.sinica.edu.tw:8081/MeInfoText2/. CONCLUSION: The previous version, MeInfoText, was developed by using association rules, whereas MeInfoText 2.0 is based on a new framework that combines machine learning, dictionary lookup and pattern matching for epigenetics information extraction. The results of experiments show that MeInfoText 2.0 outperforms existing tools in many respects. To the best of our knowledge, this is the first study that uses a hybrid approach to extract gene methylation-cancer relations. It is also the first attempt to develop a gene methylation and cancer relation corpus.

BACKGROUND: Experimentally verified protein-protein interactions (PPIs) cannot be easily retrieved by researchers unless they are stored in PPI databases. The curation of such databases can be facilitated by employing text-mining systems to identify genes which play the interactor role in PPIs and to map these genes to unique database identifiers (interactor normalization task or INT) and then to return a list of interaction pairs for each article (interaction pair task or IPT). These two tasks are evaluated in terms of the area under curve of the interpolated precision/recall (AUC iP/R) score because the order of identifiers in the output list is important for ease of curation. RESULTS: Our INT system developed for the BioCreAtIvE II.5 INT challenge achieved a promising AUC iP/R of 43.5% by using a support vector machine (SVM)-based ranking procedure. Using our new re-ranking algorithm, we have been able to improve system performance (AUC iP/R) by 1.84%. Our experimental results also show that with the re-ranked INT results, our unsupervised IPT system can achieve a competitive AUC iP/R of 23.86%, which outperforms the best BC II.5 INT system by 1.64%. Compared to using only SVM ranked INT results, using re-ranked INT results boosts AUC iP/R by 7.84%. Statistical significance t-test results show that our INT/IPT system with re-ranking outperforms that without re-ranking by a statistically significant difference. CONCLUSIONS: In this paper, we present a new re-ranking algorithm that considers co-occurrence among identifiers in an article to improve INT and IPT ranking results. Combining the re-ranked INT results with an unsupervised approach to find associations among interactors, the proposed method can boost the IPT performance. We also implement score computation using dynamic programming, which is faster and more efficient than traditional approaches.

BACKGROUND: Gene normalization (GN) is the task of identifying the unique database IDs of genes and proteins in literature. The best-known public competition of GN systems is the GN task of the BioCreative challenge, which has been held four times since 2003. The last two BioCreatives, II.5 & III, had two significant differences from earlier tasks: firstly, they provided full-length articles in addition to abstracts; and secondly, they included multiple species without providing species ID information. Full papers introduce more complex targets for GN processing, while the inclusion of multiple species vastly increases the potential size of dictionaries needed for GN. BioCreative III GN uses Threshold Average Precision at a median of k errors per query (TAP-k), a new measure closely related to the well-known average precision, but also reflecting the reliability of the score provided by each GN system. RESULTS: To use full-paper text, we employed a multi-stage GN algorithm and a ranking method which exploit information in different sections and parts of a paper. To handle the inclusion of multiple unknown species, we developed two context-based dynamic strategies to select dictionary entries related to the species that appear in the paper-section-wide and article-wide context. Our originally submitted BioCreative III system uses a static dictionary containing only the most common species entries. It already exceeds the BioCreative III average team performance by at least 24% in every evaluation. However, using our proposed dynamic dictionary strategies, we were able to further improve TAP-5, TAP-10, and TAP-20 by 16.47%, 13.57% and 6.01%, respectively in the Gold 50 test set. Our best dynamic strategy outperforms the best BioCreative III systems in TAP-10 on the Silver 50 test set and in TAP-5 on the Silver 507 set. CONCLUSIONS: Our experimental results demonstrate the superiority of our proposed dynamic dictionary selection strategies over our original static strategy and most BioCreative III participant systems. Section-wide dynamic strategy is preferred because it achieves very similar TAP-k scores to article-wide dynamic strategy but it is more efficient.

The goal of Gene Normalization (GN) is to identify the unique database IDs of genes and proteins mentioned in biomedical literature. A major difficulty in GN comes from the ambiguity of gene names. That is, the same gene name can refer to different database IDs depending on the species in question. In this paper, we introduce a method to exploit contextual information in an abstract, like tissue type, chromosome location, etc., to tackle this problem. Using this technique, we have been able to improve system performance (F-score) by 14.3% on the BioCreAtIvE-II GN task test set. We also examined our method on a full-text dataset with cross-species genes. The experimental results show a promising performance (AUC) of 42.94%. Our experimental results also show that with full text, versus abstract only, the system performance was 12.24% higher.

The interactor normalization task (INT) is to identify genes that play the interactor role in protein-protein interactions (PPIs), to map these genes to unique IDs, and to rank them according to their normalized confidence. INT has two subtasks: gene normalization (GN) and interactor ranking. The main difficulties of INT GN are identifying genes across species and using full papers instead of abstracts. To tackle these problems, we developed a multistage GN algorithm and a ranking method, which exploit information in different parts of a paper. Our system achieved a promising AUC of 0.43471. Using the multistage GN algorithm, we have been able to improve system performance (AUC) by 1.719 percent compared to a one-stage GN algorithm. Our experimental results also show that with full text, versus abstract only, INT AUC performance was 22.6 percent higher.

Abstract Summary: PubMed-EX is a browser extension that marks up PubMed search results with additional text-mining information. PubMed-EX's page mark-up, which includes section categorization and gene/disease and relation mark-up, can help researchers to quickly focus on key terms and provide additional information on them. All text processing is performed server-side, freeing up user resources. Availability: PubMed-EX is freely available at http://bws.iis.sinica.edu.tw/PubMed-EX and http://iisr.cse.yzu.edu.tw:8000/PubMed-EX/. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

BACKGROUND: The genetic factors leading to hypertension have been extensively studied, and large numbers of research papers have been published on the subject. One of hypertension researchers' primary research tasks is to locate key hypertension-related genes in abstracts. However, gathering such information with existing tools is not easy: (1) Searching for articles often returns far too many hits to browse through. (2) The search results do not highlight the hypertension-related genes discovered in the abstract. (3) Even though some text mining services mark up gene names in the abstract, the key genes investigated in a paper are still not distinguished from other genes. To facilitate the information gathering process for hypertension researchers, one solution would be to extract the key hypertension-related genes in each abstract. Three major tasks are involved in the construction of this system: (1) gene and hypertension named entity recognition, (2) section categorization, and (3) gene-hypertension relation extraction. RESULTS: We first compare the retrieval performance achieved by individually adding template features and position features to the baseline system. Then, the combination of both is examined. We found that using position features can almost double the original AUC score (0.8140 vs.0.4936) of the baseline system. However, adding template features only results in marginal improvement (0.0197). Including both improves AUC to 0.8184, indicating that these two sets of features are complementary, and do not have overlapping effects. We then examine the performance in a different domain--diabetes, and the result shows a satisfactory AUC of 0.83. CONCLUSION: Our approach successfully exploits template features to recognize true hypertension-related gene mentions and position features to distinguish key genes from other related genes. Templates are automatically generated and checked by biologists to minimize labor costs. Our approach integrates the advantages of machine learning models and pattern matching. To the best of our knowledge, this the first systematic study of extracting hypertension-related genes and the first attempt to create a hypertension-gene relation corpus based on the GAD database. Furthermore, our paper proposes and tests novel features for extracting key hypertension genes, such as relative position, section, and template features, which could also be applied to key-gene extraction for other diseases.