Grouping 34 Chemicals Based on Mode of Action Using Connectivity Mapping

• DOI: 10.1093/toxsci/kfw058
• Publication Date: 2016-03-30T00:19:09Z
• Authors: K. Nadira De Abrew; Raghunandan M. Ka...; Yuqing K. Shan; Gary J. Overmann; Raja S. Settivari; Xiaohong Wang; Jun Xu; Rachel L. Adams; Jay P. Tiesman; Edward W. Carney; Jorge M. Naciff; George P. Daston
• Keywords: Vorinostat; Mode of Action

Connectivity mapping is a method used in the pharmaceutical industry to find connections between small molecules, disease states, and genes. The concept can be applied predictive toxicology paradigm chemicals, adverse events, In order assess applicability of technique for purposes, we performed gene array experiments on 34 different chemicals: bisphenol A, genistein, ethinyl-estradiol, tamoxifen, clofibrate, dehydorepiandrosterone, troglitazone, diethylhexyl phthalate, flutamide, trenbolone, phenobarbital, retinoic acid, thyroxine, 1α,25-dihydroxyvitamin D3, clobetasol, farnesol, chenodeoxycholic progesterone, RU486, ketoconazole, valproic desferrioxamine, amoxicillin, 6-aminonicotinamide, metformin, phenformin, methotrexate, vinblastine, ANIT (1-naphthyl isothiocyanate), griseofulvin, nicotine, imidacloprid, vorinostat, 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) at 6-, 24-, 48-hour time points 3 concentrations 4 cell lines: MCF7, Ishikawa, HepaRG, HepG2 GEO (super series accession no.: GSE69851). chemicals were grouped predefined mode action (MOA)–based chemical classes based current literature. was linkages each classes. Cell line–specific compared with other test whether platform user independent, similar analysis against publicly available data. study showed that group MOAs inter–chemical class comparison alluded not predefined. Comparison data independent. results provide an example alternate process high-content data, beneficial toxicology, especially when grouping read across purposes.