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A Community Challenge for Pancancer Drug Mechanism of Action Inference from Perturbational Profile Data

View ORCID ProfileEugene F Douglass Jr., View ORCID ProfileRobert J Allaway, View ORCID ProfileBence Szalai, Wenyu Wang, View ORCID ProfileTingzhong Tian, View ORCID ProfileAdrià Fernández-Torras, Ron Realubit, View ORCID ProfileCharles Karan, View ORCID ProfileShuyu Zheng, View ORCID ProfileAlberto Pessia, View ORCID ProfileZiaurrehman Tanoli, View ORCID ProfileMohieddin Jafari, View ORCID ProfileFangping Wan, Shuya Li, Yuanpeng Xiong, View ORCID ProfileMiquel Duran-Frigola, View ORCID ProfileMartino Bertoni, View ORCID ProfilePau Badia-i-Mompel, Lídia Mateo, View ORCID ProfileOriol Guitart-Pla, View ORCID ProfileVerena Chung, DREAM CTD-squared Pancancer Drug Activity Challenge Consortium, Jing Tang, Jianyang Zeng, View ORCID ProfilePatrick Aloy, View ORCID ProfileJulio Saez-Rodriguez, View ORCID ProfileJustin Guinney, Daniela S. Gerhard, View ORCID ProfileAndrea Califano
doi: https://doi.org/10.1101/2020.12.21.423514
Eugene F Douglass Jr.
1 Pharmaceutical and Biomedical Sciences, University of Georgia, 250 W. Green Street, Athens, GA 30602;
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Robert J Allaway
2 Computational Oncology Group, Sage Bionetworks, 2901 Third Ave, Ste 330, Seattle, WA USA 98121;
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Bence Szalai
3 Semmelweis University, Faculty of Medicine, Department of Physiology, Budapest, Hungary;
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Wenyu Wang
4 Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland;
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Tingzhong Tian
5 Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, 100084, China;
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Adrià Fernández-Torras
6 Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain;
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Ron Realubit
7 Department of Systems Biology, Columbia University Irving Medical Center, 1130 Saint Nicholas Ave, New York, NY USA 10032;
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Charles Karan
7 Department of Systems Biology, Columbia University Irving Medical Center, 1130 Saint Nicholas Ave, New York, NY USA 10032;
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Shuyu Zheng
4 Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland;
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Alberto Pessia
4 Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland;
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Ziaurrehman Tanoli
4 Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland;
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Mohieddin Jafari
4 Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland;
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Fangping Wan
5 Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, 100084, China;
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Shuya Li
5 Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, 100084, China;
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Yuanpeng Xiong
5 Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, 100084, China;
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Miquel Duran-Frigola
6 Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain;
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Martino Bertoni
6 Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain;
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Pau Badia-i-Mompel
6 Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain;
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Lídia Mateo
6 Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain;
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Oriol Guitart-Pla
6 Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain;
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Verena Chung
2 Computational Oncology Group, Sage Bionetworks, 2901 Third Ave, Ste 330, Seattle, WA USA 98121;
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Jing Tang
8 esearch Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland;
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Jianyang Zeng
5 Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, 100084, China;
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Patrick Aloy
6 Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain;
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Julio Saez-Rodriguez
9 Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany;
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Justin Guinney
2 Computational Oncology Group, Sage Bionetworks, 2901 Third Ave, Ste 330, Seattle, WA USA 98121;
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Daniela S. Gerhard
10 Office of Cancer Genomics, National Cancer Institute, NIH, Bethesda, MD 20892
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Andrea Califano
7 Department of Systems Biology, Columbia University Irving Medical Center, 1130 Saint Nicholas Ave, New York, NY USA 10032;
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  • For correspondence: ac2248@cumc.columbia.edu
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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 Statement

A.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.

Footnotes

  • Author typo corrected.

  • https://www.doi.org/10.7303/syn20968331

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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A Community Challenge for Pancancer Drug Mechanism of Action Inference from Perturbational Profile Data
Eugene F Douglass Jr., Robert J Allaway, Bence Szalai, Wenyu Wang, Tingzhong Tian, Adrià Fernández-Torras, Ron Realubit, Charles Karan, Shuyu Zheng, Alberto Pessia, Ziaurrehman Tanoli, Mohieddin Jafari, Fangping Wan, Shuya Li, Yuanpeng Xiong, Miquel Duran-Frigola, Martino Bertoni, Pau Badia-i-Mompel, Lídia Mateo, Oriol Guitart-Pla, Verena Chung, DREAM CTD-squared Pancancer Drug Activity Challenge Consortium, Jing Tang, Jianyang Zeng, Patrick Aloy, Julio Saez-Rodriguez, Justin Guinney, Daniela S. Gerhard, Andrea Califano
bioRxiv 2020.12.21.423514; doi: https://doi.org/10.1101/2020.12.21.423514
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A Community Challenge for Pancancer Drug Mechanism of Action Inference from Perturbational Profile Data
Eugene F Douglass Jr., Robert J Allaway, Bence Szalai, Wenyu Wang, Tingzhong Tian, Adrià Fernández-Torras, Ron Realubit, Charles Karan, Shuyu Zheng, Alberto Pessia, Ziaurrehman Tanoli, Mohieddin Jafari, Fangping Wan, Shuya Li, Yuanpeng Xiong, Miquel Duran-Frigola, Martino Bertoni, Pau Badia-i-Mompel, Lídia Mateo, Oriol Guitart-Pla, Verena Chung, DREAM CTD-squared Pancancer Drug Activity Challenge Consortium, Jing Tang, Jianyang Zeng, Patrick Aloy, Julio Saez-Rodriguez, Justin Guinney, Daniela S. Gerhard, Andrea Califano
bioRxiv 2020.12.21.423514; doi: https://doi.org/10.1101/2020.12.21.423514

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