EDDY-CTRP is an effort to discover pathways enriched with differential dependency between drug-sensitive and non-sensitive cancer cell lines and potential mediators of drug response. This is enabled by:

The EDDY-CTRP analysis discovered ~9,000 statistically significant compound-pathway pairs and corresponding differential dependency networks (DDNs: ) across 368 different compounds, and ~27,000 compound-mediator pairs, where mediator refers to a gene that plays a significantly different role in a pathway between drug sensitive and resistant cell lines. We predict that these drug-mediator pairs have potential as testable hypotheses on drug sensitivity.

Establishing statistical correspondence between compounds and mediators can improve understanding of known gene dependencies associated with drug response while also discovering new dependencies. By incorporating STITCH and STRING databases, which catalogue chemical-protein and protein-protein interactions, we constructed evidence networks [] for ~14,400 compound-mediator pairs for support [PMID: 28617226].

G. Speyer, D. Mahendra, H. J. Tran, J. Kiefer, S. L. Schreiber, P. A. Clemons, H. Dhruv, M. Berens, and S. Kim, "Differential Dependency Pathway Discovery Associated with Drug Response across Cancer Cell Lines," Proceedings of the Pacific Symposium on Biocomputing 22, 497-508 (2017).
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[ Data Used for EDDY-CTRP Analysis ]


Contact: Seungchan Kim (skim [at] tgen.org)

Credit: Gil Speyer, Hai Joey Tran, Divya Mahendra, Jeff Kiefer

This work was supported in part by the National Cancer Institute, National Institutes of Health [1U01CA168397].
Divya Mahendra and Hai Tran were supported by the Helios Education Foundation through the Helios Scholars at TGen summer internship program in biomedical research at the Translational Genomics Research Institute in Phoenix, Arizona.