Title
Reconstructing tumor-wise protein expression in tissue microarray studies using a Bayesian cell mixture model.
Abstract
Tissue microarrays (TMAs) quantify tissue-specific protein expression of cancer biomarkers via high-density immuno-histochemical staining assays. Standard analysis approach estimates a sample mean expression in the tumor, ignoring the complex tissue-specific staining patterns observed on tissue arrays.In this article, a cell mixture model (CMM) is proposed to reconstruct tumor expression patterns in TMA experiments. The concept is to assemble the whole-tumor expression pattern by aggregating over the subpopulation of tissue specimens sampled by needle biopsies. The expression pattern in each individual tissue element is assumed to be a zero-augmented Gamma distribution to assimilate the non-staining areas and the staining areas. A hierarchical Bayes model is imposed to borrow strength across tissue specimens and across tumors. A joint model is presented to link the CMM expression model with a survival model for censored failure time observations. The implementation involves imputation steps within each Markov chain Monte Carlo iteration and Monte Carlo integration technique.The model-based approach provides estimates for various tumor expression characteristics including the percentage of staining, mean intensity of staining and a composite meanstaining to associate with patient survival outcome.R package to fit CMM model is available at http://www.mskcc.org/mskcc/html/85130.cfm
Year
DOI
Venue
2008
10.1093/bioinformatics/btn536
Bioinformatics
Keywords
Field
DocType
sample mean expression,tumor-wise protein expression,expression pattern,whole-tumor expression pattern,bayesian cell mixture model,various tumor expression characteristic,tissue-specific protein expression,tissue specimen,tumor expression pattern,cell mixture model,cmm expression model,cmm model,tissue microarray study,protein expression,mixture model,tissue microarray
Biology,Markov chain Monte Carlo,Markov chain,Tissue Array Analysis,Tissue microarray,Monte Carlo integration,Bioinformatics,Protein microarray,Mixture model,Bayes' theorem
Journal
Volume
Issue
ISSN
24
24
1367-4811
Citations 
PageRank 
References 
0
0.34
1
Authors
3
Name
Order
Citations
PageRank
Ronglai Shen11266.83
Jeremy M. G. Taylor2523.81
Debashis Ghosh349649.16