@article {Douglass2020.12.21.423514, author = {Eugene F Douglass, Jr. and Robert J Allaway and Bence Szalai and Wenyu Wang and Tingzhong Tian and Adri{\`a} Fern{\'a}ndez-Torras and Ron Realubit and Charles Karan and Shuyu Zheng and Alberto Pessia and Ziaurrehman Tanoli and Mohieddin Jafari and Fangping Wan and Shuya Li and Yuanpeng Xiong and Miquel Duran-Frigola and Martino Bertoni and Pau Badia-i-Mompel and L{\'\i}dia Mateo and Oriol Guitart-Pla and Verena Chung and DREAM CTD-squared Pancancer Drug Activity Challenge Consortium and Jing Tang and Jianyang Zeng and Patrick Aloy and Julio Saez-Rodriguez and Justin Guinney and Daniela S. Gerhard and Andrea Califano}, title = {A Community Challenge for Pancancer Drug Mechanism of Action Inference from Perturbational Profile Data}, elocation-id = {2020.12.21.423514}, year = {2020}, doi = {10.1101/2020.12.21.423514}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The Columbia Cancer Target Discovery and Development (CTD2) Center has developed PANACEA (PANcancer Analysis of Chemical Entity Activity), a collection of dose-response curves and perturbational profiles for 400 clinical oncology drugs in cell lines selected to optimally represent 19 cancer subtypes. This resource, developed to study tumor-specific drug mechanism of action, was instrumental in hosting a DREAM Challenge to assess computational models for de novo drug polypharmacology prediction. Dose-response and perturbational profiles for 32 kinase inhibitors were provided to 21 participating teams who were asked to predict high-affinity binding target among 255 possible protein kinases. Best performing methods leveraged both gene expression profile similarity analysis, and deep-learning methodologies trained on individual datasets. This study lays the foundation for future integrative analyses of pharmacogenomic data, reconciliation of polypharmacology effects in different tumor contexts, and insights into network-based assessment of context-specific drug mechanism of action.Competing Interest StatementA.C. is founder, equity holder, and consultant of DarwinHealth Inc., a company that has licensed the PANACEA database used in this manuscript from Columbia University. Columbia University is also an equity holder in DarwinHealth Inc. Other authors declare no conflicts of interest.}, URL = {https://www.biorxiv.org/content/early/2020/12/23/2020.12.21.423514}, eprint = {https://www.biorxiv.org/content/early/2020/12/23/2020.12.21.423514.full.pdf}, journal = {bioRxiv} }