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Primary Publication
Percha B, Altman RBA (2017) A global network of biomedical relationships derived from text. Bioinformatics, 34(15): 2614-2624. (2018)  View
Abstract

MOTIVATION: The biomedical community's collective understanding of how chemicals, genes and phenotypes interact is distributed across the text of over 24 million research articles. These interactions offer insights into the mechanisms behind higher order biochemical phenomena, such as drug-drug interactions and variations in drug response across individuals. To assist their curation at scale, we must understand what relationship types are possible and map unstructured natural language descriptions onto these structured classes. We used NCBI's PubTator annotations to identify instances of chemical, gene and disease names in Medline abstracts and applied the Stanford dependency parser to find connecting dependency paths between pairs of entities in single sentences. We combined a published ensemble biclustering algorithm (EBC) with hierarchical clustering to group the dependency paths into semantically-related categories, which we annotated with labels, or 'themes' ('inhibition' and 'activation', for example). We evaluated our theme assignments against six human-curated databases: DrugBank, Reactome, SIDER, the Therapeutic Target Database, OMIM and PharmGKB. RESULTS: Clustering revealed 10 broad themes for chemical-gene relationships, 7 for chemical-disease, 10 for gene-disease and 9 for gene-gene. In most cases, enriched themes corresponded directly to known database relationships. Our final dataset, represented as a network, contained 37 491 thematically-labeled chemical-gene edges, 2 021 192 chemical-disease edges, 136 206 gene-disease edges and 41 418 gene-gene edges, each representing a single-sentence description of an interaction from somewhere in the literature. AVAILABILITY AND IMPLEMENTATION: The complete network is available on Zenodo (https://zenodo.org/record/1035500). We have also provided the full set of dependency paths connecting biomedical entities in Medline abstracts, with associated sentences, for future use by the biomedical research community. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Related Publications
Percha B, Altman RB (2015) Learning the Structure of Biomedical Relationships from Unstructured Text. PLoS Comput Biol 11(7): e1004216. https://doi.org/10.1371/journal.pcbi.1004216 (2015)  View
Abstract

The published biomedical research literature encompasses most of our understanding of how drugs interact with gene products to produce physiological responses (phenotypes). Unfortunately, this information is distributed throughout the unstructured text of over 23 million articles. The creation of structured resources that catalog the relationships between drugs and genes would accelerate the translation of basic molecular knowledge into discoveries of genomic biomarkers for drug response and prediction of unexpected drug-drug interactions. Extracting these relationships from natural language sentences on such a large scale, however, requires text mining algorithms that can recognize when different-looking statements are expressing similar ideas. Here we describe a novel algorithm, Ensemble Biclustering for Classification (EBC), that learns the structure of biomedical relationships automatically from text, overcoming differences in word choice and sentence structure. We validate EBC's performance against manually-curated sets of (1) pharmacogenomic relationships from PharmGKB and (2) drug-target relationships from DrugBank, and use it to discover new drug-gene relationships for both knowledge bases. We then apply EBC to map the complete universe of drug-gene relationships based on their descriptions in Medline, revealing unexpected structure that challenges current notions about how these relationships are expressed in text. For instance, we learn that newer experimental findings are described in consistently different ways than established knowledge, and that seemingly pure classes of relationships can exhibit interesting chimeric structure. The EBC algorithm is flexible and adaptable to a wide range of problems in biomedical text mining.

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