Title
Integrative clustering of multiple genomic data types using a joint latent variable model with application to breast and lung cancer subtype analysis.
Abstract
The molecular complexity of a tumor manifests itself at the genomic, epigenomic, transcriptomic and proteomic levels. Genomic profiling at these multiple levels should allow an integrated characterization of tumor etiology. However, there is a shortage of effective statistical and bioinformatic tools for truly integrative data analysis. The standard approach to integrative clustering is separate clustering followed by manual integration. A more statistically powerful approach would incorporate all data types simultaneously and generate a single integrated cluster assignment.We developed a joint latent variable model for integrative clustering. We call the resulting methodology iCluster. iCluster incorporates flexible modeling of the associations between different data types and the variance-covariance structure within data types in a single framework, while simultaneously reducing the dimensionality of the datasets. Likelihood-based inference is obtained through the Expectation-Maximization algorithm.We demonstrate the iCluster algorithm using two examples of joint analysis of copy number and gene expression data, one from breast cancer and one from lung cancer. In both cases, we identified subtypes characterized by concordant DNA copy number changes and gene expression as well as unique profiles specific to one or the other in a completely automated fashion. In addition, the algorithm discovers potentially novel subtypes by combining weak yet consistent alteration patterns across data types.R code to implement iCluster can be downloaded at http://www.mskcc.org/mskcc/html/85130.cfm
Year
DOI
Venue
2009
10.1093/bioinformatics/btp659
Bioinformatics/computer Applications in The Biosciences
Keywords
DocType
Volume
joint latent,supplementary data,multiple genomic data type,separate clustering,maximization algorithm,resulting methodology icluster,different data type,data type,gene expression data,icluster algorithm,variable model,lung cancer subtype analysis,integrative data analysis,integrative clustering,breast cancer,biomedical research,text mining,gene expression profiling,computational biology,algorithms,statistical power,gene expression,latent variable model,bioinformatics,copy number,expectation maximization algorithm,cluster analysis,data analysis
Journal
26
Issue
ISSN
Citations 
2
1367-4811
59
PageRank 
References 
Authors
3.31
4
3
Name
Order
Citations
PageRank
Ronglai Shen11266.83
Adam B Olshen217917.38
Marc Ladanyi3593.31