A bayesian analysis strategy for cross-study translation of gene expression biomarkers.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lucas, J; Carvalho, C; West, M

Published Date

  • January 2009

Published In

Volume / Issue

  • 8 /

Start / End Page

  • Article - 11

PubMed ID

  • 19222378

Pubmed Central ID

  • 19222378

Electronic International Standard Serial Number (EISSN)

  • 1544-6115

International Standard Serial Number (ISSN)

  • 2194-6302

Digital Object Identifier (DOI)

  • 10.2202/1544-6115.1436

Language

  • eng