caa a22 4500 528784218 20190918042302.0 cr unu---uuuuu 180924e201509 xx s 000 0 eng 10.3929/ethz-b-000109369 doi 10.1038/nbt.3299 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/109369 Prediction of human population responses to toxic compounds by a collaborative competition [Elektronische Daten] [Federica Eduati, Lara M. Mangravite, Tao Wang, Hao Tang, J.C. Bare, Ruili Huang, Thea Norman, Mike Kellen, Michael P. Menden, Jichen Yang, Xiaowei Zhan, Rui Zhong, Guanghua Xiao, Menghang Xia, Nour Abdo, Oksana Kosyk, The NIEHS-NCATS-UNC DREAM Toxicogenetics Collaboration, Stephen Friend, Allen Dearry, Anton Simeonov, Raymond R. Tice, Ivan Rusyn, Fred A. Wright, Gustavo Stolovitzky, Yang Xie, Julio Saez-Rodriguez] Open access ethresearch The ability to computationally predict the effects of toxic compounds on humans could help address the deficiencies of current chemical safety testing. Here, we report the results from a community-based DREAM challenge to predict toxicities of environmental compounds with potential adverse health effects for human populations. We measured the cytotoxicity of 156 compounds in 884 lymphoblastoid cell lines for which genotype and transcriptional data are available as part of the Tox21 1000 Genomes Project. The challenge participants developed algorithms to predict interindividual variability of toxic response from genomic profiles and population-level cytotoxicity data from structural attributes of the compounds. 179 submitted predictions were evaluated against an experimental data set to which participants were blinded. Individual cytotoxicity predictions were better than random, with modest correlations (Pearson's r < 0.28), consistent with complex trait genomic prediction. In contrast, predictions of population-level response to different compounds were higher (r < 0.66). The results highlight the possibility of predicting health risks associated with unknown compounds, although risk estimation accuracy remains suboptimal. Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International http://creativecommons.org/licenses/by-nc-sa/4.0 ethresearch Health occupations ethresearch High-throughput screening ethresearch Predictive medicine ethresearch Risk factors ethresearch Eduati Federica joint author Mangravite Lara M. joint author Wang Tao joint author Tang Hao joint author Bare J.C. joint author Huang Ruili joint author Norman Thea joint author Kellen Mike joint author Menden Michael P. joint author Yang Jichen joint author Zhan Xiaowei joint author Zhong Rui joint author Xiao Guanghua joint author Xia Menghang joint author Abdo Nour joint author Kosyk Oksana joint author The NIEHS-NCATS-UNC DREAM Toxicogenetics Collaboration joint author Friend Stephen joint author Dearry Allen joint author Simeonov Anton joint author Tice Raymond R. joint author Rusyn Ivan joint author Wright Fred A. joint author Stolovitzky Gustavo joint author Xie Yang joint author Saez-Rodriguez Julio joint author Nature Biotechnology New York, NY : Nature Publishing Group 33 (9), pp. 933-940 http://hdl.handle.net/20.500.11850/109369 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/109369 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Eduati Federica joint author ETHRESEARCH 700 1- Mangravite Lara M. joint author ETHRESEARCH 700 1- Wang Tao joint author ETHRESEARCH 700 1- Tang Hao joint author ETHRESEARCH 700 1- Bare J.C. joint author ETHRESEARCH 700 1- Huang Ruili joint author ETHRESEARCH 700 1- Norman Thea joint author ETHRESEARCH 700 1- Kellen Mike joint author ETHRESEARCH 700 1- Menden Michael P. joint author ETHRESEARCH 700 1- Yang Jichen joint author ETHRESEARCH 700 1- Zhan Xiaowei joint author ETHRESEARCH 700 1- Zhong Rui joint author ETHRESEARCH 700 1- Xiao Guanghua joint author ETHRESEARCH 700 1- Xia Menghang joint author ETHRESEARCH 700 1- Abdo Nour joint author ETHRESEARCH 700 1- Kosyk Oksana joint author ETHRESEARCH 700 -- The NIEHS-NCATS-UNC DREAM Toxicogenetics Collaboration joint author ETHRESEARCH 700 1- Friend Stephen joint author ETHRESEARCH 700 1- Dearry Allen joint author ETHRESEARCH 700 1- Simeonov Anton joint author ETHRESEARCH 700 1- Tice Raymond R. joint author ETHRESEARCH 700 1- Rusyn Ivan joint author ETHRESEARCH 700 1- Wright Fred A. joint author ETHRESEARCH 700 1- Stolovitzky Gustavo joint author ETHRESEARCH 700 1- Xie Yang joint author ETHRESEARCH 700 1- Saez-Rodriguez Julio joint author ETHRESEARCH 773 0- Nature Biotechnology New York, NY : Nature Publishing Group 33 (9), pp. 933-940 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access