Computational discovery of transcription factors associated with drug response.

摘要: 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) a novel methodology that elucidates regulatory contexts associated cytotoxicity. The method, GENMi (Gene Expression iN the Middle), postulates single-nucleotide polymorphisms within TF-binding putatively modulate its activity, resulting variation expression leads to response. Analysis 161 TFs 24 treatments revealed 334 significantly TF–treatment pairs. Investigation 20 selected pairs yielded literature support for 13 these associations, often studies where perturbation TF changes Experimental validation significant associations taxanes anthracyclines across two triple-negative breast cancer corroborates our findings. method is shown be more sensitive than an alternative, genome-wide association study-based approach does not use expression. These results demonstrate utility identifying influence provide number candidates further testing.