Logo image
Incorporating network structure in integrative analysis of cancer prognosis data
Journal article   Open access   Peer reviewed

Incorporating network structure in integrative analysis of cancer prognosis data

Jin Liu, Jian Huang and Shuangge Ma
Genetic epidemiology, Vol.37(2), pp.173-183
02/2013
DOI: 10.1002/gepi.21697
PMCID: PMC3909475
PMID: 23161517

View Online

Abstract

In high-throughput cancer genomic studies, markers identified from the analysis of single datasets may have unsatisfactory properties because of low sample sizes. Integrative analysis pools and analyzes raw data from multiple studies, and can effectively increase sample size and lead to improved marker identification results. In this study, we consider the integrative analysis of multiple high-throughput cancer prognosis studies. In the existing integrative analysis studies, the interplay among genes, which can be described using the network structure, has not been effectively accounted for. In network analysis, tightly connected nodes (genes) are more likely to have related biological functions and similar regression coefficients. The goal of this study is to develop an analysis approach that can incorporate the gene network structure in integrative analysis. To this end, we adopt an AFT (accelerated failure time) model to describe survival. A weighted least squares approach, which has low computational cost, is adopted for estimation. For marker selection, we propose a new penalization approach. The proposed penalty is composed of two parts. The first part is a group MCP penalty, and conducts gene selection. The second part is a Laplacian penalty, and smoothes the differences of coefficients for tightly connected genes. A group coordinate descent approach is developed to compute the proposed estimate. Simulation study shows satisfactory performance of the proposed approach when there exist moderate-to-strong correlations among genes. We analyze three lung cancer prognosis datasets, and demonstrate that incorporating the network structure can lead to the identification of important genes and improved prediction performance.
Lung Neoplasms - genetics Models, Theoretical High-Throughput Screening Assays Prognosis Neoplasms - genetics Lung Neoplasms - mortality Computer Simulation Humans Neoplasms - mortality Gene Regulatory Networks

Details

Logo image