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Inferring causal molecular networks: Empirical assessment through a community-based effort
, Article Nature Methods ; Volume 13, Issue 4 , 2016 , Pages 310-322 ; 15487091 (ISSN) ; Heiser, L.M ; Cokelaer, T ; Linger, M ; Nesser, N. K ; Carlin, D. E ; Zhang, Y ; Sokolov, A ; Paull, E. O ; Wong, C. K ; Graim, K ; Bivol, A ; Wang, H ; Zhu, F ; Afsari, B ; Danilova, L. V ; Favorov, A. V ; Lee, W. S ; Taylor, D ; Hu, C. W ; Long, B. L ; Noren, D. P ; Bisberg, A. J ; Mills, G. B ; Gray, J. W ; Kellen, M ; Norman, T ; Friend, S ; Qutub, A. A ; Fertig, E. J ; Guan, Y ; Song, M ; Stuart, J. M ; Spellman, P. T ; Koeppl, H ; Stolovitzky, G ; Saez Rodriguez, J ; Mukherjee, S ; Afsari, B ; Al-Ouran, R ; Anton, B ; Arodz, T ; Askari Sichani, O ; Bagheri, N ; Berlow, N ; Bisberg, A. J ; Bivol, A ; Bohler, A ; Bonet, J ; Bonneau, R ; Budak, G ; Bunescu, R ; Caglar, M ; Cai, B ; Cai, C ; Carlin, D. E ; Carlon, A ; Chen, L ; Ciaccio, M. F ; Cokelaer, T ; Cooper, G ; Coort, S ; Creighton, C. J ; Daneshmand, S. M. H ; De La Fuente, A ; Di Camillo, B ; Danilova, L. V ; Dutta-Moscato, J ; Emmett, K ; Evelo, C ; Fassia, M. K. H ; Favorov, A. V ; Fertig, E. J ; Finkle, J. D ; Finotello, F ; Friend, S ; Gao, X ; Gao, J ; Garcia Garcia, J ; Ghosh, S ; Giaretta, A ; Graim, K ; Gray, J. W ; Großeholz, R ; Guan, Y ; Guinney, J ; Hafemeister, C ; Hahn, O ; Haider, S ; Hase, T ; Heiser, L. M ; Hill, S. M ; Hodgson, J ; Hoff, B ; Hsu, C. H ; Hu, C. W ; Hu, Y ; Huang, X ; Jalili, M ; Jiang, X ; Kacprowski, T ; Kaderali, L ; Kang, M ; Kannan, V ; Kellen, M ; Kikuchi, K ; Kim, D. C ; Kitano, H ; Knapp, B ; Komatsoulis, G ; Koeppl, H ; Krämer, A ; Kursa, M. B ; Kutmon, M ; Lee, W. S ; Li, Y ; Liang, X ; Liu, Z ; Liu, Y ; Long, B. L ; Lu, S ; Lu, X ; Manfrini, M ; Matos, M. R. A ; Meerzaman, D ; Mills, G. B ; Min, W ; Mukherjee, S ; Müller, C. L ; Neapolitan, R. E ; Nesser, N. K ; Noren, D. P ; Norman, T ; Oliva, B ; Opiyo, S. O ; Pal, R ; Palinkas, A ; Paull, E. O ; Planas Iglesias, J ; Poglayen, D ; Qutub, A. A ; Saez Rodriguez, J ; Sambo, F ; Sanavia, T ; Sharifi-Zarchi, A ; Slawek, J ; Sokolov, A ; Song, M ; Spellman, P. T ; Streck, A ; Stolovitzky, G ; Strunz, S ; Stuart, J. M ; Taylor, D ; Tegnér, J ; Thobe, K ; Toffolo, G. M ; Trifoglio, E ; Unger, M ; Wan, Q ; Wang, H ; Welch, L ; Wong, C. K ; Wu, J. J ; Xue, A. Y ; Yamanaka, R ; Yan, C ; Zairis, S ; Zengerling, M ; Zenil, H ; Zhang, S ; Zhang, Y ; Zhu, F ; Zi, Z ; Sharif University of Technology
Nature Publishing Group
2016
Abstract
It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was...