Text mining of gene-phenotype associations reveals new phenotypic profiles of autism-associated genes.
Ontology highlight
ABSTRACT:
SUBMITTER: Li S
PROVIDER: S-EPMC8316556 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Gene-phenotype associations play an important role in understanding the disease mechanisms which is a requirement for treatment development. A portion of gene-phenotype associations are observed mainly experimentally and made publicly available through several standard resources such as MGI. However, there is still a vast amount of gene-phenotype associations buried in the biomedical literature. Given the large amount of literature data, we need automated text mining tools to alleviate the burden in manual curation of gene-phenotype associations and to develop comprehensive resources. In this study, we present an ontology-based approach in combination with statistical methods to text mine gene-phenotype associations from the literature. Our method achieved AUC values of 0.90 and 0.75 in recovering known gene-phenotype associations from HPO and MGI respectively. We posit that candidate genes and their relevant diseases should be expressed with similar phenotypes in publications. Thus, we demonstrate the utility of our approach by predicting disease candidate genes based on the semantic similarities of phenotypes associated with genes and diseases. To the best of our knowledge, this is the first study using an ontology based approach to extract gene-phenotype associations from the literature. We evaluated our disease candidate prediction model on the gene-disease associations from MGI. Our model achieved AUC values of 0.90 and 0.87 on OMIM (human) and MGI (mouse) datasets of gene-disease associations respectively. Our manual analysis on the text mined data revealed that our method can accurately extract gene-phenotype associations which are not currently covered by the existing public gene-phenotype resources. Overall, results indicate that our method can precisely extract known as well as new gene-phenotype associations from literature. All the data and methods are available at https://github.com/bio-ontology-research-group/genepheno.
| S-EPMC6391585 | biostudies-literature
Project description:Though the genetic etiology of autism is complex, our understanding can be improved by identifying genes and gene-gene interactions that contribute to the development of specific autism subtypes. Identifying such gene groupings will allow individuals to be diagnosed and treated according to their precise characteristics. To this end, we developed a method to associate gene combinations with groups with shared autism traits, targeting genetic elements that distinguish patient populations with opposing phenotypes. Our computational method prioritizes genetic variants for genome-wide association, then utilizes Frequent Pattern Mining to highlight potential interactions between variants. We introduce a novel genotype assessment metric, the Unique Inherited Combination support, which accounts for inheritance patterns observed in the nuclear family while estimating the impact of genetic variation on phenotype manifestation at the individual level. High-contrast variant combinations are tested for significant subgroup associations. We apply this method by contrasting autism subgroups defined by severe or mild manifestations of a phenotype. Significant associations connected 286 genes to the subgroups, including 193 novel autism candidates. 71 pairs of genes have joint associations with subgroups, presenting opportunities to investigate interacting functions. This study analyzed 12 autism subgroups, but our informatics method can explore other meaningful divisions of autism patients, and can further be applied to reveal precise genetic associations within other phenotypically heterogeneous disorders, such as Alzheimer's disease.
| S-EPMC5788310 | biostudies-literature
Project description:Tens of thousands of biomedical journals exist, and the deluge of new articles in the biomedical sciences is leading to information overload. Hence, there is much interest in text mining, the use of computational tools to enhance the human ability to parse and understand complex text.
| S-EPMC2735884 | biostudies-literature
Project description:BackgroundPhenotypic information locked away in unstructured narrative text presents significant barriers to information accessibility, both for clinical practitioners and for computerised applications used for clinical research purposes. Text mining (TM) techniques have previously been applied successfully to extract different types of information from text in the biomedical domain. They have the potential to be extended to allow the extraction of information relating to phenotypes from free text.MethodsTo stimulate the development of TM systems that are able to extract phenotypic information from text, we have created a new corpus (PhenoCHF) that is annotated by domain experts with several types of phenotypic information relating to congestive heart failure. To ensure that systems developed using the corpus are robust to multiple text types, it integrates text from heterogeneous sources, i.e., electronic health records (EHRs) and scientific articles from the literature. We have developed several different phenotype extraction methods to demonstrate the utility of the corpus, and tested these methods on a further corpus, i.e., ShARe/CLEF 2013.ResultsEvaluation of our automated methods showed that PhenoCHF can facilitate the training of reliable phenotype extraction systems, which are robust to variations in text type. These results have been reinforced by evaluating our trained systems on the ShARe/CLEF corpus, which contains clinical records of various types. Like other studies within the biomedical domain, we found that solutions based on conditional random fields produced the best results, when coupled with a rich feature set.ConclusionsPhenoCHF is the first annotated corpus aimed at encoding detailed phenotypic information. The unique heterogeneous composition of the corpus has been shown to be advantageous in the training of systems that can accurately extract phenotypic information from a range of different text types. Although the scope of our annotation is currently limited to a single disease, the promising results achieved can stimulate further work into the extraction of phenotypic information for other diseases. The PhenoCHF annotation guidelines and annotations are publicly available at https://code.google.com/p/phenochf-corpus.
| S-EPMC4474585 | biostudies-literature
Project description:A considerable effort has been devoted to retrieve systematically information for genes and proteins as well as relationships between them. Despite the importance of chemical compounds and drugs as a central bio-entity in pharmacological and biological research, only a limited number of freely available chemical text-mining/search engine technologies are currently accessible. Here we present LimTox (Literature Mining for Toxicology), a web-based online biomedical search tool with special focus on adverse hepatobiliary reactions. It integrates a range of text mining, named entity recognition and information extraction components. LimTox relies on machine-learning, rule-based, pattern-based and term lookup strategies. This system processes scientific abstracts, a set of full text articles and medical agency assessment reports. Although the main focus of LimTox is on adverse liver events, it enables also basic searches for other organ level toxicity associations (nephrotoxicity, cardiotoxicity, thyrotoxicity and phospholipidosis). This tool supports specialized search queries for: chemical compounds/drugs, genes (with additional emphasis on key enzymes in drug metabolism, namely P450 cytochromes-CYPs) and biochemical liver markers. The LimTox website is free and open to all users and there is no login requirement. LimTox can be accessed at: http://limtox.bioinfo.cnio.es.
| S-EPMC5570141 | biostudies-literature
Project description:Text mining in biomedical literature is an emerging field which has already been shown to have a variety of implementations in many research areas, including genetics, personalized medicine, and pharmacogenomics. In this study, we describe a novel text-mining approach for the extraction of pharmacogenomics associations. The code that was used toward this end was implemented using R programming language, either through custom scripts, where needed, or through utilizing functions from existing libraries. Articles (abstracts or full texts) that correspond to a specified query were extracted from PubMed, while concept annotations were derived by PubTator Central. Terms that denote a Mutation or a Gene as well as Chemical compound terms corresponding to drug compounds were normalized and the sentences containing the aforementioned terms were filtered and preprocessed to create appropriate training sets. Finally, after training and adequate hyperparameter tuning, four text classifiers were created and evaluated (FastText, Linear kernel SVMs, XGBoost, Lasso, and Elastic-Net Regularized Generalized Linear Models) with regard to their performance in identifying pharmacogenomics associations. Although further improvements are essential toward proper implementation of this text-mining approach in the clinical practice, our study stands as a comprehensive, simplified, and up-to-date approach for the identification and assessment of research articles enriched in clinically relevant pharmacogenomics relationships. Furthermore, this work highlights a series of challenges concerning the effective application of text mining in biomedical literature, whose resolution could substantially contribute to the further development of this field.
| S-EPMC7748107 | biostudies-literature
Project description:Mental disorders are important diseases with a high prevalence rate in the general population. Common mental disorders are complex diseases with high heritability, and their pathogenesis is the result of interactions between genetic and environmental factors. However, the relationship between mental disorders and genes is complex and difficult to evaluate. Additionally, some mental disorders involve numerous genes, and a single gene can also be associated with different types of mental disorders.This study used text mining (including word frequency analysis, cluster analysis, and association analysis) of the PubMed database to identify genes related to mental disorders.Word frequency analysis revealed 52 high-frequency genes important in studies of mental disorders. Cluster analysis showed that 5-HTT, SLC6A4, and MAOA are common genetic factors in most mental disorders; the intra-group genes in each cluster were highly correlated. Some mental disorders may have common genetic factors; for example, there may be common genetic factors between 'Affective Disorders' and 'Schizophrenia.' Association analysis revealed 35 frequent itemsets and 25 association rules, indicating close associations among genes. The results of association rules showed that CCK, MAOA, and 5-HTT are the most closely related.We used text mining technology to analyze genes related to mental disorders to further summarize and clarify the relationships between mental disorders and genes as well as identify potential relationships, providing a foundation for future experiments. The results of the associative analysis also provide a reference for multi-gene studies of mental disorders.
| S-EPMC6824703 | biostudies-literature
Project description:BackgroundBlood cancers (BCs) are responsible for over 720 K yearly deaths worldwide. Their prevalence and mortality-rate uphold the relevance of research related to BCs. Despite the availability of different resources establishing Disease-Disease Associations (DDAs), the knowledge is scattered and not accessible in a straightforward way to the scientific community. Here, we propose SicknessMiner, a biomedical Text-Mining (TM) approach towards the centralization of DDAs. Our methodology encompasses Named Entity Recognition (NER) and Named Entity Normalization (NEN) steps, and the DDAs retrieved were compared to the DisGeNET resource for qualitative and quantitative comparison.ResultsWe obtained the DDAs via co-mention using our SicknessMiner or gene- or variant-disease similarity on DisGeNET. SicknessMiner was able to retrieve around 92% of the DisGeNET results and nearly 15% of the SicknessMiner results were specific to our pipeline.ConclusionsSicknessMiner is a valuable tool to extract disease-disease relationship from RAW input corpus.
| S-EPMC8491382 | biostudies-literature
Project description:The practice of precision medicine will ultimately require databases of genes and mutations for healthcare providers to reference in order to understand the clinical implications of each patient's genetic makeup. Although the highest quality databases require manual curation, text mining tools can facilitate the curation process, increasing accuracy, coverage, and productivity. However, to date there are no available text mining tools that offer high-accuracy performance for extracting such triplets from biomedical literature. In this paper we propose a high-performance machine learning approach to automate the extraction of disease-gene-variant triplets from biomedical literature. Our approach is unique because we identify the genes and protein products associated with each mutation from not just the local text content, but from a global context as well (from the Internet and from all literature in PubMed). Our approach also incorporates protein sequence validation and disease association using a novel text-mining-based machine learning approach. We extract disease-gene-variant triplets from all abstracts in PubMed related to a set of ten important diseases (breast cancer, prostate cancer, pancreatic cancer, lung cancer, acute myeloid leukemia, Alzheimer's disease, hemochromatosis, age-related macular degeneration (AMD), diabetes mellitus, and cystic fibrosis). We then evaluate our approach in two ways: (1) a direct comparison with the state of the art using benchmark datasets; (2) a validation study comparing the results of our approach with entries in a popular human-curated database (UniProt) for each of the previously mentioned diseases. In the benchmark comparison, our full approach achieves a 28% improvement in F1-measure (from 0.62 to 0.79) over the state-of-the-art results. For the validation study with UniProt Knowledgebase (KB), we present a thorough analysis of the results and errors. Across all diseases, our approach returned 272 triplets (disease-gene-variant) that overlapped with entries in UniProt and 5,384 triplets without overlap in UniProt. Analysis of the overlapping triplets and of a stratified sample of the non-overlapping triplets revealed accuracies of 93% and 80% for the respective categories (cumulative accuracy, 77%). We conclude that our process represents an important and broadly applicable improvement to the state of the art for curation of disease-gene-variant relationships.
| S-EPMC5130168 | biostudies-literature
Project description:Advances in the next generation sequencing technology has accelerated the pace of individualized medicine (IM), which aims to incorporate genetic/genomic information into medicine. One immediate need in interpreting sequencing data is the assembly of information about genetic variants and their corresponding associations with other entities (e.g., diseases or medications). Even with dedicated effort to capture such information in biological databases, much of this information remains 'locked' in the unstructured text of biomedical publications. There is a substantial lag between the publication and the subsequent abstraction of such information into databases. Multiple text mining systems have been developed, but most of them focus on the sentence level association extraction with performance evaluation based on gold standard text annotations specifically prepared for text mining systems.We developed and evaluated a text mining system, MutD, which extracts protein mutation-disease associations from MEDLINE abstracts by incorporating discourse level analysis, using a benchmark data set extracted from curated database records. MutD achieves an F-measure of 64.3% for reconstructing protein mutation disease associations in curated database records. Discourse level analysis component of MutD contributed to a gain of more than 10% in F-measure when compared against the sentence level association extraction. Our error analysis indicates that 23 of the 64 precision errors are true associations that were not captured by database curators and 68 of the 113 recall errors are caused by the absence of associated disease entities in the abstract. After adjusting for the defects in the curated database, the revised F-measure of MutD in association detection reaches 81.5%.Our quantitative analysis reveals that MutD can effectively extract protein mutation disease associations when benchmarking based on curated database records. The analysis also demonstrates that incorporating discourse level analysis significantly improved the performance of extracting the protein-mutation-disease association. Future work includes the extension of MutD for full text articles.
| S-EPMC4457984 | biostudies-literature