Journal Article

Reconstructing tumor-wise protein expression in tissue microarray studies using a Bayesian cell mixture model

Ronglai Shen, Jeremy M. G. Taylor and Debashis Ghosh

in Bioinformatics

Volume 24, issue 24, pages 2880-2886
Published in print December 2008 | ISSN: 1367-4803
Published online October 2008 | e-ISSN: 1460-2059 | DOI:
Reconstructing tumor-wise protein expression in tissue microarray studies using a Bayesian cell mixture model

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Motivation: 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.

Methods: 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.

Results: 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.

Availability: R package to fit CMM model is available at


Supplementary information: Supplementary data are available at Bioinformatics online.

Journal Article.  4223 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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