학술논문
Genetic dependencies associated with transcription factor activities in human cancer cell lines
Document Type
article
Author
Venu Thatikonda; Verena Supper; Johannes Wachter; Onur Kaya; Anju Kombara; Ceren Bilgilier; Madhwesh C. Ravichandran; Jesse J. Lipp; Rahul Sharma; Lukas Badertscher; Andrew S. Boghossian; Matthew G. Rees; Melissa M. Ronan; Jennifer A. Roth; Sarah Grosche; Ralph A. Neumüller; Barbara Mair; Federico Mauri; Alexandra Popa
Source
Cell Reports, Vol 43, Iss 5, Pp 114175- (2024)
Subject
Language
English
ISSN
2211-1247
Abstract
Summary: Transcription factors (TFs) are important mediators of aberrant transcriptional programs in cancer cells. In this study, we focus on TF activity (TFa) as a biomarker for cell-line-selective anti-proliferative effects, in that high TFa predicts sensitivity to loss of function of a given gene (i.e., genetic dependencies [GDs]). Our linear-regression-based framework identifies 3,047 pan-cancer and 3,952 cancer-type-specific candidate TFa-GD associations from cell line data, which are then cross-examined for impact on survival in patient cohorts. One of the most prominent biomarkers is TEAD1 activity, whose associations with its predicted GDs are validated through experimental evidence as proof of concept. Overall, these TFa-GD associations represent an attractive resource for identifying innovative, biomarker-driven hypotheses for drug discovery programs in oncology.