Journal article
Integrative Analysis of Cancer Prognosis Data With Multiple Subtypes Using Regularized Gradient Descent
Genetic epidemiology, Vol.36(8), pp.829-838
12/2012
DOI: 10.1002/gepi.21669
PMCID: PMC3729731
PMID: 22851516
Abstract
In cancer research, high-throughput profiling studies have been extensively conducted, searching for genes/single nucleotide polymorphisms (SNPs) associated with prognosis. Despite seemingly significant differences, different subtypes of the same cancer (or different types of cancers) may share common susceptibility genes. In this study, we analyze prognosis data on multiple subtypes of the same cancer but note that the proposed approach is directly applicable to the analysis of data on multiple types of cancers. We describe the genetic basis of multiple subtypes using the heterogeneity model that allows overlapping but different sets of susceptibility genes/SNPs for different subtypes. An accelerated failure time (AFT) model is adopted to describe prognosis. We develop a regularized gradient descent approach that conducts gene-level analysis and identifies genes that contain important SNPs associated with prognosis. The proposed approach belongs to the family of gradient descent approaches, is intuitively reasonable, and has affordable computational cost. Simulation study shows that when prognosis-associated SNPs are clustered in a small number of genes, the proposed approach outperforms alternatives with significantly more true positives and fewer false positives. We analyze an NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements and identify genes associated with the three major subtypes of NHL, namely, DLBCL, FL, and CLL/SLL. The proposed approach identifies genes different from using alternative approaches and has the best prediction performance. © 2012 Wiley Periodicals, Inc.
Details
- Title: Subtitle
- Integrative Analysis of Cancer Prognosis Data With Multiple Subtypes Using Regularized Gradient Descent
- Creators
- Shuangge Ma - Yale UniversityYawei Zhang - Yale UniversityJian Huang - University of IowaYuan Huang - Pennsylvania State UniversityQing Lan - National Cancer InstituteNathaniel Rothman - National Cancer InstituteTongzhang Zheng - Yale University
- Resource Type
- Journal article
- Publication Details
- Genetic epidemiology, Vol.36(8), pp.829-838
- DOI
- 10.1002/gepi.21669
- PMID
- 22851516
- PMCID
- PMC3729731
- NLM abbreviation
- Genet Epidemiol
- ISSN
- 0741-0395
- eISSN
- 1098-2272
- Publisher
- Blackwell Publishing Ltd
- Number of pages
- 10
- Language
- English
- Date published
- 12/2012
- Academic Unit
- Statistics and Actuarial Science; Biostatistics
- Record Identifier
- 9984257746102771
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