title: Integrative genomic testing of cancer survival using semiparametric linear transformation models.
abstract: The wide availability of multi-dimensional genomic data has spurred increasing interests in integrating multi-platform genomic data. Integrative analysis of cancer genome landscape can potentially lead to deeper understanding of the biological process of cancer. We integrate epigenetics (DNA methylation and microRNA expression) and gene expression data in tumor genome to delineate the association between different aspects of the biological processes and brain tumor survival. To model the association, we employ a flexible semiparametric linear transformation model that incorporates both the main effects of these genomic measures as well as the possible interactions among them. We develop variance component tests to examine different coordinated effects by testing various subsets of model coefficients for the genomic markers. A Monte Carlo perturbation procedure is constructed to approximate the null distribution of the proposed test statistics. We further propose omnibus testing procedures to synthesize information from fitting various parsimonious sub-models to improve power. Simulation results suggest that our proposed testing procedures maintain proper size under the null and outperform standard score tests. We further illustrate the utility of our procedure in two genomic analyses for survival of glioblastoma multiforme patients. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Departments of Epidemiology and Biostatistics, Brown University, 121 South Main St.Box G-S121-2 Providence, 02912, RI, U.S.A.
authors.forename: Yen-Tsung
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Department of Biostatistics, School of Public Health, Harvard University, 655 Huntington Ave., Boston, 02115, MA, U.S.A.
authors.forename: Tianxi
authors.initials: T
authors.lastname: Cai
authors.affiliation: Office of Biostatistics National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Building 10/Rm 5N230, Bethesda, 20892, MD.
authors.forename: Eunhee
authors.identifier: 0000-0002-7252-7202
authors.initials: E
authors.lastname: Kim
mesh_terms: D001699:Biometry; D057890:Epigenomics; D023281:Genomics; D005909:Glioblastoma / Q000235:genetics / Q000401:mortality; D006801:Humans; D016014:Linear Models; D009369:Neoplasms / Q000235:genetics* / Q000401:mortality
keywords: integrative genomics; linear transformation model; mediation analysis; survival analysis; variance component test