Abstract 6591: A universal atlas of cellular and oncogenic phenotypes

Abstract Tumors and healthy tissues exhibit gene expression variability in many of the same pathways. We propose that these commonalities result from a performance trade-off between universal cellular phenotypes; each phenotype is defined by an orthogonal gene expression profile identified using unsupervised dimensionality reduction. Using two publicly available RNA-seq datasets (n=54 normal tissues; n=1504 cancer cell lines), we show that both healthy and cancerous cells occupy a trade-off between five canonical phenotypes: OxPhos, Warburg, Fibroblastic, Immune, and Growth. Each cell is assigned a phenotype score that, as we demonstrate, predicts differential drug sensitivities and mutational signatures, even among cancers of the same tissue type. Since these phenotype scores are defined using only healthy tissues, they can be generally applied to other diseases as well. Citation Format: Corey Weistuch, Kevin Murgas, Ken Dill, Larry Norton, Joseph Deasy, Allen Tannenbaum. A universal atlas of cellular and oncogenic phenotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6591.