A Bayesian Approach for Learning Gene Networks Underlying Disease Severity in COPD

Elin Shaddox, Francesco C. Stingo, Christine B. Peterson, Sean Jacobson, Charmion Cruickshank-Quinn, Katerina Kechris, Russell Bowler, Marina Vannucci

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

In this paper, we propose a Bayesian hierarchical approach to infer network structures across multiple sample groups where both shared and differential edges may exist across the groups. In our approach, we link graphs through a Markov random field prior. This prior on network similarity provides a measure of pairwise relatedness that borrows strength only between related groups. We incorporate the computational efficiency of continuous shrinkage priors, improving scalability for network estimation in cases of larger dimensionality. Our model is applied to patient groups with increasing levels of chronic obstructive pulmonary disease severity, with the goal of better understanding the break down of gene pathways as the disease progresses. Our approach is able to identify critical hub genes for four targeted pathways. Furthermore, it identifies gene connections that are disrupted with increased disease severity and that characterize the disease evolution. We also demonstrate the superior performance of our approach with respect to competing methods, using simulated data.

Original languageEnglish (US)
Pages (from-to)59-85
Number of pages27
JournalStatistics in Biosciences
Volume10
Issue number1
DOIs
StatePublished - Apr 1 2018

Keywords

  • Bayesian inference
  • Chronic obstructive pulmonary disease (COPD)
  • Gaussian graphical model
  • Gene network
  • Markov random field prior
  • Spike-and-slab prior

ASJC Scopus subject areas

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

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