Robert Tibshirani

Publication Details

• Analysis of factorial time-course microarrays with application to a clinical study of burn injury.

  Zhou B, Xu W, Herndon D, Tompkins R, Davis R, Xiao W, Wong WH, Toner M, Warren HS, Schoenfeld DA, Rahme L, McDonald-Smith GP, Hayden D, Mason P, Fagan S, Yu YM, Cobb JP, Remick DG, Mannick JA, Lederer JA, Gamelli RL, Silver GM, West MA, Shapiro MB, Smith R, Camp DG, Qian W, Storey J, Mindrinos M, Tibshirani R, Lowry S, Calvano S, Chaudry I, West MA, Cohen M, Moore EE, Johnson J, Moldawer LL, Baker HV, Efron PA, Balis UG, Billiar TR, Ochoa JB, Sperry JL, Miller-Graziano CL, De AK, Bankey PE, Finnerty CC, Jeschke MG, Minei JP, Arnoldo BD, Hunt JL, Horton J, Cobb JP, Brownstein B, Freeman B, Maier RV, Nathens AB, Cuschieri J, Gibran N, Klein M, O'Keefe G. Proc Natl Acad Sci U S A. 2010; 107 (22): 9923-8

  Time-course microarray experiments are capable of capturing dynamic gene expression profiles. It is important to study how these dynamic profiles depend on the multiple factors that characterize the experimental condition under which the time course is observed. Analytic methods are needed to simultaneously handle the time course and factorial structure in the data. We developed a method to evaluate factor effects by pooling information across the time course while accounting for multiple testing and nonnormality of the microarray data. The method effectively extracts gene-specific response features and models their dependency on the experimental factors. Both longitudinal and cross-sectional time-course data can be handled by our approach. The method was used to analyze the impact of age on the temporal gene response to burn injury in a large-scale clinical study. Our analysis reveals that 21% of the genes responsive to burn are age-specific, among which expressions of mitochondria and immunoglobulin genes are differentially perturbed in pediatric and adult patients by burn injury. These new findings in the body's response to burn injury between children and adults support further investigations of therapeutic options targeting specific age groups. The methodology proposed here has been implemented in R package "TANOVA" and submitted to the Comprehensive R Archive Network at http://www.r-project.org/. It is also available for download at http://gluegrant1.stanford.edu/TANOVA/.

  PubMedID: 20479259