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A Bayesian Analysis Strategy for Cross-Study Translation of Gene Expression Biomarkers


  • Lucas Joseph

    (Duke Institute for Genome Sciences and Policy)

  • Carvalho Carlos

    (University of Chicago Graduate School of Business)

  • West Mike

    (Duke Department of Statistical Science)


We describe a strategy for the analysis of experimentally derived gene expression signatures and their translation to human observational data. Sparse multivariate regression models are used to identify expression signature gene sets representing downstream biological pathway events following interventions in designed experiments. When translated into in vivo human observational data, analysis using sparse latent factor models can yield multiple quantitative factors characterizing expression patterns that are often more complex than in the controlled, in vitro setting. The estimation of common patterns in expression that reflect all aspects of covariation evident in vivo offers an enhanced, modular view of the complexity of biological associations of signature genes. This can identify substructure in the biological process under experimental investigation and improved biomarkers of clinical outcomes. We illustrate the approach in a detailed study from an oncogene intervention experiment where in vivo factor profiling of an in vitro signature generates biological insights related to underlying pathway activities and chromosomal structure, and leads to refinements of cancer recurrence risk stratification across several cancer studies.

Suggested Citation

  • Lucas Joseph & Carvalho Carlos & West Mike, 2009. "A Bayesian Analysis Strategy for Cross-Study Translation of Gene Expression Biomarkers," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 8(1), pages 1-26, February.
  • Handle: RePEc:bpj:sagmbi:v:8:y:2009:i:1:n:11

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    References listed on IDEAS

    1. Carvalho, Carlos M. & Chang, Jeffrey & Lucas, Joseph E. & Nevins, Joseph R. & Wang, Quanli & West, Mike, 2008. "High-Dimensional Sparse Factor Modeling: Applications in Gene Expression Genomics," Journal of the American Statistical Association, American Statistical Association, vol. 103(484), pages 1438-1456.
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    Cited by:

    1. Bonassi Fernando V. & You Lingchong & West Mike, 2011. "Bayesian Learning from Marginal Data in Bionetwork Models," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 10(1), pages 1-27, October.
    2. Zheng Lingling & Yan Xiao & Suchindran Sunil & Dressman Holly & Chute John P. & Lucas Joseph, 2014. "Biological pathway selection through Bayesian integrative modeling," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 13(6), pages 1-1, December.

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