Computational discovery of transcription factors associated with drug response.

ABSTRACT: This study integrates gene expression, genotype and drug response data in lymphoblastoid cell lines with transcription factor (TF)-binding sites from ENCODE (Encyclopedia of Genomic Elements) in a novel methodology that elucidates regulatory contexts associated with cytotoxicity. The method, GENMi (Gene Expression iN the Middle), postulates that single-nucleotide polymorphisms within TF-binding sites putatively modulate its regulatory activity, and the resulting variation in gene expression leads to variation in drug response. Analysis of 161 TFs and 24 treatments revealed 334 significantly associated TF-treatment pairs. Investigation of 20 selected pairs yielded literature support for 13 of these associations, often from studies where perturbation of the TF expression changes drug respons

SUBMITTER: Hanson C 

PROVIDER: S-EPMC4848185 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature