A Bayesian Analysis Strategy for Cross-Study Translation of Gene Expression Biomarkers
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.
If you experience problems downloading a file, check if you have the proper application to view it first. In case of further problems read the IDEAS help page. Note that these files are not on the IDEAS site. Please be patient as the files may be large.
As the access to this document is restricted, you may want to look for a different version under "Related research" (further below) or search for a different version of it.
Volume (Year): 8 (2009)
Issue (Month): 1 (February)
|Contact details of provider:|| Web page: https://www.degruyter.com|
|Order Information:||Web: https://www.degruyter.com/view/j/sagmb|
References listed on IDEAS
Please report citation or reference errors to , or , if you are the registered author of the cited work, log in to your RePEc Author Service profile, click on "citations" and make appropriate adjustments.:
- 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.