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

Zhao, W.; Li, J.; Chen, M.-J.; Ju, Z.; Nesser, N.; Johnson-Camacho, K.; Boniface, C.; Lawrence, Y.; Pande, N.; Davies, M.; Herlyn, M.; Muranen, T.; Zervantonakis, I.; Von Euw, E.; Schultz, A.; Kumar, S.; Korkut, A.; Spellman, P.; Akbani, R.; Slamon, D.; Gray, J.; Brugge, J.; Lu, Y.; Mills, G.; Liang, H.

doi:10.1101/2020.07.03.186908

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bioRxiv · 10.1101/2020.07.03.186908

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

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Abstract

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. HighlightsO_LIA large collection of cancer cell line protein responses to drug perturbations C_LIO_LIPerturbed protein responses greatly increase predictive power for drug sensitivity C_LIO_LIBuild a systematic map of protein-drug connectivity based on response profiles C_LIO_LIDevelop a user-friendly, interactive data portal for community use C_LI

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Zhao, W., Li, J., Chen, M.-J., Ju, Z., Nesser, N., Johnson-Camacho, K., Boniface, C., Lawrence, Y., Pande, N., Davies, M., Herlyn, M., Muranen, T., Zervantonakis, I., Von Euw, E., Schultz, A., Kumar, S., Korkut, A., Spellman, P., Akbani, R., Slamon, D., Gray, J., Brugge, J., Lu, Y., Mills, G., Liang, H.. 2020-07-04. Large-scale Characterization of Drug Responses of Clinically Relevant Proteins in Cancer Cell Lines. https://doi.org/10.1101/2020.07.03.186908

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