title: Prediction of drug gene associations via ontological profile similarity with application to drug repositioning.
abstract: The amount of biomedical literature has been increasing rapidly during the last decade. Text mining techniques can harness this large-scale data, shed light onto complex drug mechanisms, and extract relation information that can support computational polypharmacology. In this work, we introduce a fully corpus-based and unsupervised method which utilizes the MEDLINE indexed titles and abstracts to infer drug gene associations and assist drug repositioning. The method measures the Pointwise Mutual Information (PMI) between biomedical terms derived from the Gene Ontology and the Medical Subject Headings. Based on the PMI scores, drug and gene profiles are generated and candidate drug gene associations are inferred when computing the relatedness of their profiles. Results show that an Area Under the Curve (AUC) of up to 0.88 can be achieved. The method can successfully identify direct drug gene associations with high precision and prioritize them. Validation shows that the statistically derived profiles from literature perform as good as manually curated profiles. In addition, we examine the potential application of our approach towards drug repositioning. For all FDA approved drugs repositioned over the last 5 years, we generate profiles from publications before 2009 and show that new indications rank high in the profiles. In summary, literature mined profiles can accurately predict drug gene associations and provide insights onto potential repositioning cases.
authors.affiliation: Biotechnology Center, Technische Universität Dresden, Germany. Electronic address: maria.kissa@biotec.tu-dresden.de.
authors.forename: Maria
authors.initials: M
authors.lastname: Kissa
authors.affiliation: Biotechnology Center, Technische Universität Dresden, Germany. Electronic address: george.tsatsaronis@biotec.tu-dresden.de.
authors.forename: George
authors.initials: G
authors.lastname: Tsatsaronis
authors.affiliation: Biotechnology Center, Technische Universität Dresden, Germany. Electronic address: ms@biotec.tu-dresden.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeder
mesh_terms: D057225:Data Mining / Q000379:methods*; D058492:Drug Repositioning / Q000379:methods*; D005544:Forecasting; D063990:Gene Ontology; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D004364:Pharmaceutical Preparations; D010597:Pharmacogenetics / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations
keywords: Drug gene association prediction; Drug repositioning; MEDLINE; Ontological profiles; Semantic relatedness; Unsupervised