Journal article
Incorporating network structure in integrative analysis of cancer prognosis data
Genetic epidemiology, Vol.37(2), pp.173-183
02/2013
DOI: 10.1002/gepi.21697
PMCID: PMC3909475
PMID: 23161517
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.
Details
- Title: Subtitle
- Incorporating network structure in integrative analysis of cancer prognosis data
- Creators
- Jin Liu - Department of Biostatistics, School of Public Health, Yale University, New Haven, CT 06520, USAJian HuangShuangge Ma
- Resource Type
- Journal article
- Publication Details
- Genetic epidemiology, Vol.37(2), pp.173-183
- DOI
- 10.1002/gepi.21697
- PMID
- 23161517
- PMCID
- PMC3909475
- NLM abbreviation
- Genet Epidemiol
- ISSN
- 0741-0395
- eISSN
- 1098-2272
- Publisher
- United States
- Grant note
- R01 CA142774 / NCI NIH HHS CA142774 / NCI NIH HHS R21 CA165923 / NCI NIH HHS R01 CA152301 / NCI NIH HHS CA152301 / NCI NIH HHS CA165923 / NCI NIH HHS
- Language
- English
- Date published
- 02/2013
- Academic Unit
- Statistics and Actuarial Science
- Record Identifier
- 9983985713502771
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