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:
EDDY which is a knowledge-assisted statistical test of differential dependency to identify pathways enriched with differential dependencies and potential therapeutic mediators
[PMID: 24500284, PMID: 26775171],
- The Cancer Cell Line Encyclopedia (CCLE) which provides deep molecular characterization of > 800 human long-term cell lines spanning several different histological types of cancer, and
- The CTD2-based Cancer Therapeutics Response Portal (CTRP) which provides drug-response measurements for 481 small molecules using CCLE-characterized cell lines and analytical tools that link sensitivity to molecular characterization.
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
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).
The results can be navigated to from the banner navigation menu.