Biomedical Literature Mining Research Articles

Biomedical literature mining: graph kernel-based learning for gene–gene interaction extraction

The supervised machine learning method is often used for biomedical relationship extraction. The disadvantage is that it requires much time and money to manually establish an annotated dataset. Based on distant supervision, the knowledge base is combined with the corpus, thus, the training corpus can be automatically annotated. As many biomedical databases provide knowledge bases for study with a limited number of annotated corpora, this method is practical in biomedicine. The clinical significance of each patient’s genetic makeup can be understood based on the healthcare provider’s genetic database. Unfortunately, the lack of previous biomedical relationship extraction studies focuses on gene–gene interaction. The main purpose of this study is to develop extraction methods for gene–gene interactions that can help explain the heritability of human complex diseases. This study referred to the information on gene–gene interactions in the KEGG PATHWAY database, the abstracts in PubMed were adopted to generate the training sample set, and the graph kernel method was adopted to extract gene–gene interactions. The best assessment result was an F1-score of 0.79. Our developed distant supervision method automatically finds sentences through the corpus without manual labeling for extracting gene–gene interactions, which can effectively reduce the time cost for manual annotation data; moreover, the relationship extraction method based on a graph kernel can be successfully applied to extract gene–gene interactions. In this way, the results of this study are expected to help achieve precision medicine.

Graph-GPA 2.0: improving multi-disease genetic analysis with integration of functional annotation data.

Genome-wide association studies (GWAS) have successfully identified a large number of genetic variants associated with traits and diseases. However, it still remains challenging to fully understand the functional mechanisms underlying many associated variants. This is especially the case when we are interested in variants shared across multiple phenotypes. To address this challenge, we propose graph-GPA 2.0 (GGPA 2.0), a statistical framework to integrate GWAS datasets for multiple phenotypes and incorporate functional annotations within a unified framework. Our simulation studies showed that incorporating functional annotation data using GGPA 2.0 not only improves the detection of disease-associated variants, but also provides a more accurate estimation of relationships among diseases. Next, we analyzed five autoimmune diseases and five psychiatric disorders with the functional annotations derived from GenoSkyline and GenoSkyline-Plus, along with the prior disease graph generated by biomedical literature mining. For autoimmune diseases, GGPA 2.0 identified enrichment for blood-related epigenetic marks, especially B cells and regulatory T cells, across multiple diseases. Psychiatric disorders were enriched for brain-related epigenetic marks, especially the prefrontal cortex and the inferior temporal lobe for bipolar disorder and schizophrenia, respectively. In addition, the pleiotropy between bipolar disorder and schizophrenia was also detected. Finally, we found that GGPA 2.0 is robust to the use of irrelevant and/or incorrect functional annotations. These results demonstrate that GGPA 2.0 can be a powerful tool to identify genetic variants associated with each phenotype or those shared across multiple phenotypes, while also promoting an understanding of functional mechanisms underlying the associated variants.

A publication-wide association study (PWAS), historical language models to prioritise novel therapeutic drug targets

Most biomedical knowledge is published as text, making it challenging to analyse using traditional statistical methods. In contrast, machine-interpretable data primarily comes from structured property databases, which represent only a fraction of the knowledge present in the biomedical literature. Crucial insights and inferences can be drawn from these publications by the scientific community. We trained language models on literature from different time periods to evaluate their ranking of prospective gene-disease associations and protein–protein interactions. Using 28 distinct historical text corpora of abstracts published between 1995 and 2022, we trained independent Word2Vec models to prioritise associations that were likely to be reported in future years. This study demonstrates that biomedical knowledge can be encoded as word embeddings without the need for human labelling or supervision. Language models effectively capture drug discovery concepts such as clinical tractability, disease associations, and biochemical pathways. Additionally, these models can prioritise hypotheses years before their initial reporting. Our findings underscore the potential for extracting yet-to-be-discovered relationships through data-driven approaches, leading to generalised biomedical literature mining for potential therapeutic drug targets. The Publication-Wide Association Study (PWAS) enables the prioritisation of under-explored targets and provides a scalable system for accelerating early-stage target ranking, irrespective of the specific disease of interest.

Exploring the effects of drug, disease, and protein dependencies on biomedical named entity recognition: A comparative analysis.

Background: Biomedical named entity recognition is one of the important tasks of biomedical literature mining. With the development of natural language processing technology, many deep learning models are used to extract valuable information from the biomedical literature, which promotes the development of effective BioNER models. However, for specialized domains with diverse and complex contexts and a richer set of semantically related entity types (e.g., drug molecules, targets, pathways, etc., in the biomedical domain), whether the dependencies of these drugs, diseases, and targets can be helpful still needs to be explored. Method: Providing additional dependency information beyond context, a method based on the graph attention network and BERT pre-training model named MKGAT is proposed to improve BioNER performance in the biomedical domain. To enhance BioNER by using external dependency knowledge, we integrate BERT-processed text embeddings and entity dependencies to construct better entity embedding representations for biomedical named entity recognition. Results: The proposed method obtains competitive accuracy and higher efficiency than the state-of-the-art method on three datasets, namely, NCBI-disease corpus, BC2GM, and BC5CDR-chem, with a precision of 90.71%, 88.19%, and 95.71%, recall of 92.52%, 88.05%, and 95.62%, and F1-scores of 91.61%, 88.12%, and 95.66%, respectively, which performs better than existing methods. Conclusion: Drug, disease, and protein dependencies can allow entities to be better represented in neural networks, thereby improving the performance of BioNER.

Context mining and graph queries on giant biomedical knowledge graphs

Contextual information is widely considered for NLP and knowledge discovery in life sciences since it highly influences the exact meaning of natural language. The scientific challenge is not only to extract such context data, but also to store this data for further query and discovery approaches. Classical approaches use RDF triple stores, which have serious limitations. Here, we propose a multiple step knowledge graph approach using labeled property graphs based on polyglot persistence systems to utilize context data for context mining, graph queries, knowledge discovery and extraction. We introduce the graph-theoretic foundation for a general context concept within semantic networks and show a proof of concept based on biomedical literature and text mining. Our test system contains a knowledge graph derived from the entirety of PubMed and SCAIView data and is enriched with text mining data and domain-specific language data using Biological Expression Language. Here, context is a more general concept than annotations. This dense graph has more than 71M nodes and 850M relationships. We discuss the impact of this novel approach with 27 real-world use cases represented by graph queries. Storing and querying a giant knowledge graph as a labeled property graph is still a technological challenge. Here, we demonstrate how our data model is able to support the understanding and interpretation of biomedical data. We present several real-world use cases that utilize our massive, generated knowledge graph derived from PubMed data and enriched with additional contextual data. Finally, we show a working example in context of biologically relevant information using SCAIView.

A Hybrid Protocol for Identifying Comorbidity-Based Potential Drugs for COVID-19 Using Biomedical Literature Mining, Network Analysis, and Deep Learning.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has spread on an unprecedented scale around the globe. Despite of 141,975 published papers on COVID-19 and several hundreds of new studies carried out every day, this pandemic remains as a global challenge. Biomedical literature mining helps the researchers to understand the etiology of the disease and to gain an in-depth knowledge of the disease, potential drugs, vaccines developed and novel therapies. In addition to the available treatments, there is a huge need to address the comorbidity-based disease mortality in case of COVID-19 patients with type 2 diabetes mellitus (T2D), hypertension and cardiovascular disease (CVD). In this chapter, we provide a hybrid protocol based on biomedical literature mining, network analysis of omics data, and deep learning for the identification of most potential drugs for COVID-19.

Integration of Transcriptomics Data and Metabolomic Data Using Biomedical Literature Mining and Pathway Analysis.

Recent progress in omics technologies such as transcriptomics and metabolomics offers an unprecedented opportunity to understand the disease mechanisms and determines the associated biomedical entities using biomedical literature mining. Tremendous data available in the biomedical literature helps in addressing complex biomedical problems. Advancements in genomics and transcriptomics helps in decoding the genetic information obtained from various high throughput techniques for its use in personalized medicine and therapeutics. Integration of data from biomedical literature and data from large-scale genomic studies aids in the determination of the etiology of a disease and drug targets. This chapter addresses the perspectives of transcriptomics and metabolomics in biomedical literature mining and gives an overview of state-of-the-art techniques in this field.

Biomedical Literature Mining and Its Components.

The published biomedical articles are the best source of knowledge to understand the importance of biomedical entities such as disease, drugs, and their role in different patient population groups. The number of biomedical literature available and being published is increasing at an exponential rate with the use of large scale experimental techniques. Manual extraction of such information is becoming extremely difficult because of the huge number of biomedical literature available. Alternatively, text mining approaches receive much interest within biomedicine by providing automatic extraction of such information in more structured format from the unstructured biomedical text. Here, a text mining protocol to extract the patient population information, to identify the disease and drug mentions in PubMed titles and abstracts, and a simple information retrieval approach to retrieve a list of relevant documents for a user query are presented. The text mining protocol presented in this chapter is useful for retrieving information on drugs for patients with a specific disease. The protocol covers three major text mining tasks, namely, information retrieval, information extraction, and knowledge discovery.

Combining Literature Mining and Machine Learning for Predicting Biomedical Discoveries.

The major outcomes and insights of scientific research and clinical study end up in the form of publication or clinical record in an unstructured text format. Due to advancements in biomedical research, the growth of published literature is getting tremendous large in recent years. The scientists and clinical researchers are facing a big challenge to stay current with the knowledge and to extract hidden information from this sheer quantity of millions of published biomedical literature. The potential one-stop automated solution to this problem is biomedical literature mining. One of the long-standing goals in biology is to discover the disease-causing genes and their specific roles in personalized precision medicine and drug repurposing. However, the empirical approaches and clinical affirmation are expensive and time-consuming. In silico approach using text mining to identify the disease causing genes can contribute towards biomarker discovery. This chapter presents a protocol on combining literature mining and machine learning for predicting biomedical discoveries with a special emphasis on gene-disease relation based discovery. The protocol is presented as a literature based discovery (LBD) pipeline for gene-disease based discovery. The protocol includes our web based tools: (1) DNER (Disease Named Entity Recognizer) for disease entity recognition, (2) BCCNER (Bidirectional, Contextual clues Named Entity Tagger) for gene/protein entity recognition, (3) DisGeReExT (Disease-Gene Relation Extractor) for statistically validated results and visualization, and (4) a newly introduced deep learning based method for association discovery. Our proposed deep learning based method can be generalized and applied to other important biomedical discoveries focusing on entities such as drug/chemical, or miRNA.

Biomedical Literature Mining for Repurposing Laboratory Tests.

Epidemiological studies identifying biological markers of disease state are valuable, but can be time-consuming, expensive, and require extensive intuition and expertise. Furthermore, not all hypothesized markers will be borne out in a study, suggesting that high-quality initial hypotheses are crucial. In this chapter, we describe a high-throughput pipeline to produce a ranked list of high-quality hypothesized biomarkers for diseases. We review an example use of this approach to generate a large number of candidate disease biomarker hypotheses derived from machine learning models, filter and rank them according to their potential novelty using text mining, and corroborate the most promising hypotheses with further statistical modeling. The example use of the pipeline uses a large electronic health record dataset and the PubMed corpus, to find several promising hypothesized laboratory tests with previously undocumented correlations to particular diseases.

Examining the Effect of the Ratio of Biomedical Domain to General Domain Data in Corpus in Biomedical Literature Mining

Biomedical terms extracted using Word2vec, the most popular word embedding model in recent years, serve as the foundation for various natural language processing (NLP) applications, such as biomedical information retrieval, relation extraction, and recommendation systems. The objective of this study is to examine how changes in the ratio of the biomedical domain to general domain data in the corpus affect the extraction of similar biomedical terms using Word2vec. We downloaded abstracts of 214,892 articles from PubMed Central (PMC) and the 3.9 GB Billion Word (BW) benchmark corpus from the computer science community. The datasets were preprocessed and grouped into 11 corpora based on the ratio of BW to PMC, ranging from 0:10 to 10:0, and then Word2vec models were trained on these corpora. The cosine similarities between the biomedical terms obtained from the Word2vec models were then compared in each model. The results indicated that the models trained with both BW and PMC data outperformed the model trained only with medical data. The similarity between the biomedical terms extracted by the Word2vec model increased when the ratio of the biomedical domain to general domain data was 3:7 to 5:5. This study allows NLP researchers to apply Word2vec based on more information and increase the similarity of extracted biomedical terms to improve their effectiveness in NLP applications, such as biomedical information extraction.

Atopic dermatitis or eczema? Consequences of ambiguity in disease name for biomedical literature mining.

Biomedical research increasingly relies on computational approaches to extract relevant information from large corpora of publications. To investigate the consequence of the ambiguity between the use of terms "Eczema" and "Atopic Dermatitis" (AD) from the Information Retrieval perspective, and its impact on meta-analyses, systematic reviews and text mining. Articles were retrieved by querying the PubMed using terms 'eczema' (D003876) and "dermatitis, atopic" (D004485). We used machine learning to investigate the differences between the contexts in which each term is used. We used a decision tree approach and trained model to predict if an article would be indexed with eczema or AD tags. We used text-mining tools to extract biological entities associated with eczema and AD, and investigated the discrepancy regarding the retrieval of key findings according to the terminology used. Atopic dermatitis query yielded more articles related to veterinary science, biochemistry, cellular and molecular biology; the eczema query linked to public health, infectious disease and respiratory system. Medical Subject Headings terms associated with "AD" or "Eczema" differed, with an agreement between the top 40lists of 52%. The presence of terms related to cellular mechanisms, especially allergies and inflammation, characterized AD literature. The metabolites mentioned more frequently than expected in articles with AD tag differed from those indexed with eczema. Fewer enriched genes were retrieved when using eczema compared to AD query. There is a considerable discrepancy when using text mining to extract bio-entities related to eczema or AD. Our results suggest that any systematic approach (particularly when looking for metabolites or genes related to the condition) should be performed using both terms jointly. We propose to use decision tree learning as a tool to spot and characterize ambiguity, and provide the source code for disambiguation at https://github.com/cfrainay/ResearchCodeBase.

Adverse Drug Reaction Discovery Using a Tumor-Biomarker Knowledge Graph.

Adverse drug reactions (ADRs) are a major public health concern, and early detection is crucial for drug development and patient safety. Together with the increasing availability of large-scale literature data, machine learning has the potential to predict unknown ADRs from current knowledge. By the machine learning methods, we constructed a Tumor-Biomarker Knowledge Graph (TBKG) which contains four types of node: Tumor, Biomarker, Drug, and ADR using biomedical literatures. Based on this knowledge graph, we not only discovered potential ADRs of antitumor drugs but also provided explanations. Experiments on real-world data show that our model can achieve 0.81 accuracy of three cross-validation and the ADRs discovery of Osimertinib was chosen for the clinical validation. Calculated ADRs of Osimertinib by our model consisted of the known ADRs which were in line with the official manual and some unreported rare ADRs in clinical cases. Results also showed that our model outperformed traditional co-occurrence methods. Moreover, each calculated ADRs were attached with the corresponding paths of “tumor-biomarker-drug” in the knowledge graph which could help to obtain in-depth insights into the underlying mechanisms. In conclusion, the tumor-biomarker knowledge-graph based approach is an explainable method for potential ADRs discovery based on biomarkers and might be valuable to the community working on the emerging field of biomedical literature mining and provide impetus for the mechanism research of ADRs.

Multiscale Laplacian graph kernel combined with lexico-syntactic patterns for biomedical event extraction from literature

Bio-event extraction is an extensive research area in the field of biomedical text mining, this focuses on elaborating relationships between biomolecules and can provide various aspects of their nature. Bio-event extraction plays a vital role in biomedical literature mining applications such as biological network construction, pathway curation, and drug repurposing. Extracting biological events automatically is a difficult task because of the uncertainty and assortment of natural language processing such as negations and speculations, which provides further room for the development of feasible methodologies. This paper presents a hybrid approach that integrates an ensemble-learning framework by combining a Multiscale Laplacian Graph kernel and a feature-based linear kernel, using a pattern-matching engine to identify biomedical events with arguments. This graph-based kernel not only captures the topological relationships between the individual event nodes but also identifies the associations among the subgraphs for complex events. In addition, the lexico-syntactic patterns were used to automatically discover the semantic role of each word in the sentence. For performance evaluation, we used the gold standard corpora, namely BioNLP-ST (2009, 2011, and 2013) and GENIA-MK. Experimental results show that our approach achieved better performance than other state-of-the-art systems.

PALMER: improving pathway annotation based on the biomedical literature mining with a constrained latent block model

BackgroundIn systems biology, it is of great interest to identify previously unreported associations between genes. Recently, biomedical literature has been considered as a valuable resource for this purpose. While classical clustering algorithms have popularly been used to investigate associations among genes, they are not tuned for the literature mining data and are also based on strong assumptions, which are often violated in this type of data. For example, these approaches often assume homogeneity and independence among observations. However, these assumptions are often violated due to both redundancies in functional descriptions and biological functions shared among genes. Latent block models can be alternatives in this case but they also often show suboptimal performances, especially when signals are weak. In addition, they do not allow to utilize valuable prior biological knowledge, such as those available in existing databases.ResultsIn order to address these limitations, here we propose PALMER, a constrained latent block model that allows to identify indirect relationships among genes based on the biomedical literature mining data. By automatically associating relevant Gene Ontology terms, PALMER facilitates biological interpretation of novel findings without laborious downstream analyses. PALMER also allows researchers to utilize prior biological knowledge about known gene-pathway relationships to guide identification of gene–gene associations. We evaluated PALMER with simulation studies and applications to studies of pathway-modulating genes relevant to cancer signaling pathways, while utilizing biological pathway annotations available in the KEGG database as prior knowledge.ConclusionsWe showed that PALMER outperforms traditional latent block models and it provides reliable identification of novel gene–gene associations by utilizing prior biological knowledge, especially when signals are weak in the biomedical literature mining dataset. We believe that PALMER and its relevant user-friendly software will be powerful tools that can be used to improve existing pathway annotations and identify novel pathway-modulating genes.

Identification of most influential co-occurring gene suites for gastrointestinal cancer using biomedical literature mining and graph-based influence maximization

BackgroundGastrointestinal (GI) cancer including colorectal cancer, gastric cancer, pancreatic cancer, etc., are among the most frequent malignancies diagnosed annually and represent a major public health problem worldwide.MethodsThis paper reports an aided curation pipeline to identify potential influential genes for gastrointestinal cancer. The curation pipeline integrates biomedical literature to identify named entities by Bi-LSTM-CNN-CRF methods. The entities and their associations can be used to construct a graph, and from which we can compute the sets of co-occurring genes that are the most influential based on an influence maximization algorithm.ResultsThe sets of co-occurring genes that are the most influential that we discover include RARA - CRBP1, CASP3 - BCL2, BCL2 - CASP3 – CRBP1, RARA - CASP3 – CRBP1, FOXJ1 - RASSF3 - ESR1, FOXJ1 - RASSF1A - ESR1, FOXJ1 - RASSF1A - TNFAIP8 - ESR1. With TCGA and functional and pathway enrichment analysis, we prove the proposed approach works well in the context of gastrointestinal cancer.ConclusionsOur pipeline that uses text mining to identify objects and relationships to construct a graph and uses graph-based influence maximization to discover the most influential co-occurring genes presents a viable direction to assist knowledge discovery for clinical applications.

Recent advances in biomedical literature mining.

The recent years have witnessed a rapid increase in the number of scientific articles in biomedical domain. These literature are mostly available and readily accessible in electronic format. The domain knowledge hidden in them is critical for biomedical research and applications, which makes biomedical literature mining (BLM) techniques highly demanding. Numerous efforts have been made on this topic from both biomedical informatics (BMI) and computer science (CS) communities. The BMI community focuses more on the concrete application problems and thus prefer more interpretable and descriptive methods, while the CS community chases more on superior performance and generalization ability, thus more sophisticated and universal models are developed. The goal of this paper is to provide a review of the recent advances in BLM from both communities and inspire new research directions.

DTranNER: biomedical named entity recognition with deep learning-based label-label transition model

BackgroundBiomedical named-entity recognition (BioNER) is widely modeled with conditional random fields (CRF) by regarding it as a sequence labeling problem. The CRF-based methods yield structured outputs of labels by imposing connectivity between the labels. Recent studies for BioNER have reported state-of-the-art performance by combining deep learning-based models (e.g., bidirectional Long Short-Term Memory) and CRF. The deep learning-based models in the CRF-based methods are dedicated to estimating individual labels, whereas the relationships between connected labels are described as static numbers; thereby, it is not allowed to timely reflect the context in generating the most plausible label-label transitions for a given input sentence. Regardless, correctly segmenting entity mentions in biomedical texts is challenging because the biomedical terms are often descriptive and long compared with general terms. Therefore, limiting the label-label transitions as static numbers is a bottleneck in the performance improvement of BioNER.ResultsWe introduce DTranNER, a novel CRF-based framework incorporating a deep learning-based label-label transition model into BioNER. DTranNER uses two separate deep learning-based networks: Unary-Network and Pairwise-Network. The former is to model the input for determining individual labels, and the latter is to explore the context of the input for describing the label-label transitions. We performed experiments on five benchmark BioNER corpora. Compared with current state-of-the-art methods, DTranNER achieves the best F1-score of 84.56% beyond 84.40% on the BioCreative II gene mention (BC2GM) corpus, the best F1-score of 91.99% beyond 91.41% on the BioCreative IV chemical and drug (BC4CHEMD) corpus, the best F1-score of 94.16% beyond 93.44% on the chemical NER, the best F1-score of 87.22% beyond 86.56% on the disease NER of the BioCreative V chemical disease relation (BC5CDR) corpus, and a near-best F1-score of 88.62% on the NCBI-Disease corpus.ConclusionsOur results indicate that the incorporation of the deep learning-based label-label transition model provides distinctive contextual clues to enhance BioNER over the static transition model. We demonstrate that the proposed framework enables the dynamic transition model to adaptively explore the contextual relations between adjacent labels in a fine-grained way. We expect that our study can be a stepping stone for further prosperity of biomedical literature mining.

Multitask learning for biomedical named entity recognition with cross-sharing structure

BackgroundBiomedical named entity recognition (BioNER) is a fundamental and essential task for biomedical literature mining, which affects the performance of downstream tasks. Most BioNER models rely on domain-specific features or hand-crafted rules, but extracting features from massive data requires much time and human efforts. To solve this, neural network models are used to automatically learn features. Recently, multi-task learning has been applied successfully to neural network models of biomedical literature mining. For BioNER models, using multi-task learning makes use of features from multiple datasets and improves the performance of models.ResultsIn experiments, we compared our proposed model with other multi-task models and found our model outperformed the others on datasets of gene, protein, disease categories. We also tested the performance of different dataset pairs to find out the best partners of datasets. Besides, we explored and analyzed the influence of different entity types by using sub-datasets. When dataset size was reduced, our model still produced positive results.ConclusionWe propose a novel multi-task model for BioNER with the cross-sharing structure to improve the performance of multi-task models. The cross-sharing structure in our model makes use of features from both datasets in the training procedure. Detailed analysis about best partners of datasets and influence between entity categories can provide guidance of choosing proper dataset pairs for multi-task training. Our implementation is available at https://github.com/JogleLew/bioner-cross-sharing.

GAIL: An interactive webserver for inference and dynamic visualization of gene-gene associations based on gene ontology guided mining of biomedical literature.

In systems biology, inference of functional associations among genes is compelling because the construction of functional association networks facilitates biomarker discovery. Specifically, such gene associations in human can help identify putative biomarkers that can be used as diagnostic tools in treating patients. Although biomedical literature is considered a valuable data source for this task, currently only a limited number of webservers are available for mining gene-gene associations from the vast amount of biomedical literature using text mining techniques. Moreover, these webservers often have limited coverage of biomedical literature and also lack efficient and user-friendly tools to interpret and visualize mined relationships among genes. To address these limitations, we developed GAIL (Gene-gene Association Inference based on biomedical Literature), an interactive webserver that infers human gene-gene associations from Gene Ontology (GO) guided biomedical literature mining and provides dynamic visualization of the resulting association networks and various gene set enrichment analysis tools. We evaluate the utility and performance of GAIL with applications to gene signatures associated with systemic lupus erythematosus and breast cancer. Results show that GAIL allows effective interrogation and visualization of gene-gene networks and their subnetworks, which facilitates biological understanding of gene-gene associations. GAIL is available at http://chunglab.io/GAIL/.