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Genetic dependencies associated with transcription factor activities in human cancer cell lines [CROP-seq]

GSE263747 Homo sapiens Expression profiling by high throughput sequencing; Other 6 samples Submitted 2024/04/29 Platform GPL24676
Summary
Transcription factors (TFs) are important mediators of aberrant transcriptional programs in cancer cells. In this study, we focused on TF activity (TFa) as a new 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 (GD)). Our linear regression-based framework identified 3,047 pan-cancer and 3,952 cancer-typespecific candidate TFa-GD associations from cell line data, which were then crossexamined for impact on survival in patient cohorts. One of the most prominent biomarkers was TEAD1 activity, whose associations with its predicted GDs were validated through experimental evidence as proof of concept. Overall, these TFa-GD associations represent an attractive resource for identifying innovative, biomarkerdriven hypotheses for drug discovery programs in oncology.
Published in
Genetic dependencies associated with transcription factor activities in human cancer cell lines
Thatikonda V, Supper V, Wachter J et al. · Cell reports 2024 · PMID 38691456 · doi:10.1016/j.celrep.2024.114175
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Also filed as BioProject PRJNA1099153 and SRA study SRP501169. Searching any of these in the dataset finder brings you back here.

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