Electrical - Electronic Engineering / Elektrik - Elektronik Mühendisliği

Permanent URI for this collectionhttps://hdl.handle.net/11147/11

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Author: search.filters.author.Heiser, Laura M.Subject: search.filters.subject.Gene expression

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  • Article
    Citation - WoS: 560
    Citation - Scopus: 607
    A Community Effort To Assess and Improve Drug Sensitivity Prediction Algorithms
    (Nature Publishing Group, 2014) Costello, James C.; Heiser, Laura M.; Georgii, Elisabeth; Gönen, Mehmet; Menden, Michael P.; Wang, Nicholas J.; Bansal, Mukesh; Ammad-ud-din, Muhammad; Hintsanen, Petteri; Khan, Suleiman A.; Mpindi, John-Patrick; Kallioniemi, Olli; Honkela, Antti; Aittokallio, Tero; Wennerberg, Krister; NCI-DREAM Community; Karaçalı, Bilge; Collins, James J.; Gallahan, Dan; Singer, Dinah; Saez-Rodriguez, Julio; Kaski, Samuel; Gray, Joe W.; Stolovitzky, Gustavo
    Predicting the best treatment strategy from genomic information is a core goal of precision medicine. Here we focus on predicting drug response based on a cohort of genomic, epigenomic and proteomic profiling data sets measured in human breast cancer cell lines. Through a collaborative effort between the National Cancer Institute (NCI) and the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we analyzed a total of 44 drug sensitivity prediction algorithms. The top-performing approaches modeled nonlinear relationships and incorporated biological pathway information. We found that gene expression microarrays consistently provided the best predictive power of the individual profiling data sets; however, performance was increased by including multiple, independent data sets. We discuss the innovations underlying the top-performing methodology, Bayesian multitask MKL, and we provide detailed descriptions of all methods. This study establishes benchmarks for drug sensitivity prediction and identifies approaches that can be leveraged for the development of new methods.
  • Article
    Citation - WoS: 240
    Citation - Scopus: 264
    A Community Computational Challenge To Predict the Activity of Pairs of Compounds
    (Nature Publishing Group, 2014) Bansal, Mukesh; Yang, Jichen; Karan, Charles; Menden, Michael P.; Costello, James C.; Tang, Hao; Xiao, Guanghua; Li, Yajuan; Allen, Jeffrey; Zhong, Rui; Chen, Beibei; Kim, Minsoo; Wang, Tao; Heiser, Laura M.; Realubit, Ronald; Mattioli, Michela; Alvarez, Mariano J.; Shen, Yao; NCI-DREAM Community; Karaçalı, Bilge; Gallahan, Daniel; Singer, Dinah; Saez-Rodriguez, Julio; Xie, Yang; Stolovitzky, Gustavo; Califano, Andrea
    Recent therapeutic successes have renewed interest in drug combinations, but experimental screening approaches are costly and often identify only small numbers of synergistic combinations. The DREAM consortium launched an open challenge to foster the development of in silico methods to computationally rank 91 compound pairs, from the most synergistic to the most antagonistic, based on gene-expression profiles of human B cells treated with individual compounds at multiple time points and concentrations. Using scoring metrics based on experimental dose-response curves, we assessed 32 methods (31 community-generated approaches and SynGen), four of which performed significantly better than random guessing. We highlight similarities between the methods. Although the accuracy of predictions was not optimal, we find that computational prediction of compound-pair activity is possible, and that community challenges can be useful to advance the field of in silico compound-synergy prediction.