title: tcTKB: an integrated cardiovascular toxicity knowledge base for targeted cancer drugs.
abstract: Targeted cancer drugs are often associated with unexpectedly high cardiovascular (CV) adverse events. Systematic approaches to studying CV events associated with targeted anticancer drugs have high potential for elucidating the complex pathways underlying targeted anti-cancer drugs. In this study, we built tcTKB, a comprehensive CV toxicity knowledge base for targeted cancer drugs, by extracting drug-CV pairs from five large-scale and complementary data sources. The data sources include FDA drug labels (44,979 labels), the FDA Adverse Event Reporting System (FAERS) (4,285,097 records), the Canada Vigilance Adverse Reaction Online Database (CVAROD) (1,107,752 records), published biomedical literature (21,354,075 records), and published full-text articles from the Journal of Oncology (JCO) (13,855 articles). tcTKB contains 14,351 drug-CV pairs for 45 targeted anticancer drugs and 1,842 CV events. We demonstrate that CV events positively correlate with drug target genes and drug metabolism genes, demonstrating that tcTKB in combination with other data resources, could facilitate our understanding of targeted anticancer drugs and their associated CV toxicities.
authors.affiliation: Department of Epidemiology and Biostatistics, Institute of Computational Biology, School of Medicine, Case Western Reserve University, Cleveland OH 44106.
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.affiliation: ThinTek, LLC, Palo Alto, CA 94306.
authors.forename: QuanQiu
authors.initials: Q
authors.lastname: Wang
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002170:Canada; D002318:Cardiovascular Diseases / Q000139:chemically induced; D057225:Data Mining; D016208:Databases, Factual; D001330:Electronic Data Processing; D006801:Humans; D051188:Knowledge Bases
chemical_list: D000970:Antineoplastic Agents