A Bayesian Approach to Pathway Analysis by Integrating Gene-Gene Functional Directions and Microarray Data

Yifang Zhao, Ming Hui Chen, Baikang Pei, David Rowe, Dong Guk Shin, Wangang Xie, Fang Yu, Lynn Kuo

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Many statistical methods have been developed to screen for differentially expressed genes associated with specific phenotypes in the microarray data. However, it remains a major challenge to synthesize the observed expression patterns with abundant biological knowledge for more complete understanding of the biological functions among genes. Various methods including clustering analysis on genes, neural network, Bayesian network and pathway analysis have been developed toward this goal. In most of these procedures, the activation and inhibition relationships among genes have hardly been utilized in the modeling steps. We propose two novel Bayesian models to integrate the microarray data with the putative pathway structures obtained from the KEGG database and the directional gene-gene interactions in the medical literature. We define the symmetric Kullback-Leibler divergence of a pathway, and use it to identify the pathway(s) most supported by the microarray data. Monte Carlo Markov Chain sampling algorithm is given for posterior computation in the hierarchical model. The proposed method is shown to select the most supported pathway in an illustrative example. Finally, we apply the methodology to a real microarray data set to understand the gene expression profile of osteoblast lineage at defined stages of differentiation. We observe that our method correctly identifies the pathways that are reported to play essential roles in modulating bone mass.

Original languageEnglish (US)
Pages (from-to)105-131
Number of pages27
JournalStatistics in Biosciences
Volume4
Issue number1
DOIs
StatePublished - May 1 2012

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Keywords

  • Bayesian belief network
  • Bayesian model selection
  • KEGG pathways
  • Microarray data
  • Prior construction
  • Symmetric Kullback-Leibler divergence

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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