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.
Lucas
Joseph
J
Duke Institute for Genome Sciences and Policy. joe@stat.duke.edu
Carvalho
Carlos
C
West
Mike
M
D001499:Bayes Theorem; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000706:statistics & numerical data*; D055106:Genome-Wide Association Study; D006801:Humans; D008957:Models, Genetic; D016011:Normal Distribution; D051419:Paxillin / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012044:Regression Analysis; D016019:Survival Analysis; D016596:Vinculin / Q000235:genetics
D015415:Biomarkers; D051419:Paxillin; D016271:Proto-Oncogene Proteins c-myc; D016596:Vinculin