Integrative Genomics with Mediation Analysis in a Survival Context. (18th December 2013)

• Record Type: Journal Article
• Authors: Nemes, Szilárd; Parris, Toshima Z.; Danielsson, Anna; Einbeigi, Zakaria; Steineck, Gunnar; Jonasson, Junmei Miao; Helou, Khalil
• Other Names: Klebanov Lev Academic Editor.
• Is Part Of: Computational and mathematical methods in medicine. Volume 2013(2013)
• Publication Date: 2013-12-18
• Subjects: Medicine -- Computer simulation -- Periodicals; Medicine -- Mathematical models -- Periodicals; 610.11
• DOI: 10.1155/2013/413783
• Languages: English
• ISSNs: 1748-670X

Abstract

Abstract : DNA copy number aberrations (DCNA) and subsequent altered gene expression profiles may have a major impact on tumor initiation, on development, and eventually on recurrence and cancer-specific mortality. However, most methods employed in integrative genomic analysis of the two biological levels, DNA and RNA, do not consider survival time. In the present note, we propose the adoption of a survival analysis-based framework for the integrative analysis of DCNA and mRNA levels to reveal their implication on patient clinical outcome with the prerequisite that the effect of DCNA on survival is mediated by mRNA levels. The specific aim of the paper is to offer a feasible framework to test the DCNA-mRNA-survival pathway. We provide statistical inference algorithms for mediation based on asymptotic results. Furthermore, we illustrate the applicability of the method in an integrative genomic analysis setting by using a breast cancer data set consisting of 141 invasive breast tumors. In addition, we provide implementation in R.