Large-scale Characterization of Drug Responses of Clinically Relevant Proteins in Cancer Cell Lines

Summary Perturbation biology is a powerful approach to developing quantitative models of cellular behaviors and gaining mechanistic insights into disease development. In recent years, large-scale resources for phenotypic and mRNA responses of cancer cell lines to perturbations have been generated. However, similar large-scale protein response resources are not available, resulting in a critical knowledge gap for elucidating oncogenic mechanisms and developing effective cancer therapies. Here we generated and compiled perturbed expression profiles of ~210 clinically relevant proteins in >12,000 cancer cell-line samples in response to >150 drug compounds using reverse-phase protein arrays. We show that integrating protein response signals substantially increases the predictive power for drug sensitivity and aids in gaining insights into mechanisms of drug resistance. We build a systematic map of protein-drug connectivity and develop an open-access, user-friendly data portal for community use. Our study provides a valuable information resource for a broad range of quantitative modeling and biomedical applications. Highlights A large collection of cancer cell line protein responses to drug perturbations Perturbed protein responses greatly increase predictive power for drug sensitivity Build a systematic map of protein-drug connectivity based on response profiles Develop a user-friendly, interactive data portal for community use