An integrative analysis of cancer gene expression studies using Bayesian latent factor modeling

DOI10.1214/09-AOAS261zbMATH Open1184.62190arXiv1010.1157WikidataQ34196222 ScholiaQ34196222MaRDI QIDQ965136FDOQ965136

Authors: Julia Ling-Yu Chen, Jen-Tsan Chi, Mike West, Daniel Merl 

Publication date: 21 April 2010

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: We present an applied study in cancer genomics for integrating data and inferences from laboratory experiments on cancer cell lines with observational data obtained from human breast cancer studies. The biological focus is on improving understanding of transcriptional responses of tumors to changes in the pH level of the cellular microenvironment. The statistical focus is on connecting experimentally defined biomarkers of such responses to clinical outcome in observational studies of breast cancer patients. Our analysis exemplifies a general strategy for accomplishing this kind of integration across contexts. The statistical methodologies employed here draw heavily on Bayesian sparse factor models for identifying, modularizing and correlating with clinical outcome these signatures of aggregate changes in gene expression. By projecting patterns of biological response linked to specific experimental interventions into observational studies where such responses may be evidenced via variation in gene expression across samples, we are able to define biomarkers of clinically relevant physiological states and outcomes that are rooted in the biology of the original experiment. Through this approach we identify microenvironment-related prognostic factors capable of predicting long term survival in two independent breast cancer datasets. These results suggest possible directions for future laboratory studies, as well as indicate the potential for therapeutic advances though targeted disruption of specific pathway components.

Full work available at URL: https://arxiv.org/abs/1010.1157

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zbMATH Keywords

acidosis and neutralization pathways in cancerBayesian latent factor modelsbreast cancer genomicsgene expression signaturesintegrative cancer genomicsmicro-environmental parameters in cancerWeibull survival models

Mathematics Subject Classification ID

Bayesian inference (62F15) Applications of statistics to biology and medical sciences; meta analysis (62P10) Medical applications (general) (92C50)

Cites Work

• Shotgun Stochastic Search for “Largep” Regression
• High-dimensional sparse factor modeling: applications in gene expression genomics
• Of mice and men: sparse statistical modeling in cardiovascular genomics
• A Bayesian analysis strategy for cross-study translation of gene expression biomarkers
• An integrative analysis of cancer gene expression studies using Bayesian latent factor modeling

Cited In (10)

• Simple Bayesian binary framework for discovering significant genes and classifying cancer diagnosis
• An integrative analysis of cancer gene expression studies using Bayesian latent factor modeling
• miRNA-target gene regulatory networks: a Bayesian integrative approach to biomarker selection with application to kidney cancer
• Modeling adverse birth outcomes via confirmatory factor quantile regression
• Using sufficient direction factor model to analyze latent activities associated with breast cancer survival
• Application of Bayesian networks for inferring cause-effect relations from gene expression profiles of cancer versus normal cells
• On integrating multi-experiment microarray data
• A Bayesian analysis strategy for cross-study translation of gene expression biomarkers
• Partial Factor Modeling: Predictor-Dependent Shrinkage for Linear Regression
• Identification of breast cancer prognosis markers via integrative analysis

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