bioRxivJClub
Predicting Pathway Dependency in Head and Neck Squamous Cell Carcinoma from Hallmark Transcriptomic Features
bioRxiv · · Preprint · Open access
Afshar, Goli
Abstract ↗AI summary
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P53 dependency in head and neck squamous cell carcinoma is inferred from baseline Hallmark transcriptomic activity with cross-validated R2 up to 0.48 in GDSC cell lines.
- Why it matters: Targeted therapies often fail because pathway activation does not equal functional dependence, and no validated method existed to infer dependence from baseline tumor profiles.
- What they did: Nine Elastic Net models used 50 MSigDB Hallmark activity profiles across 953 GDSC cell lines with pooled drug responses per pathway, then were validated with pharmacological, genomic, and proteomic data.
- The result: In TCGA-HNSC (n = 565) and GSE65858 (n = 256), HPV status is linked to greater P53 dependency among TP53-wild-type tumors (beta = +0.37, q = 0.010), enabling pathway-directed agent matching.
The findingWhy it mattersWhat they didThe result
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