Bayesian Analysis of iTRAQ Data with Nonrandom Missingness: Identification of Differentially Expressed Proteins

被引:0
|
作者
Luo, Ruiyan [1 ]
Colangelo, Christopher M. [2 ]
Sessa, William C. [3 ]
Zhao, Hongyu [1 ]
机构
[1] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA
[2] Yale Univ, WM Keck Fdn, Sch Med, Biotechnol Resource Lab, New Haven, CT 06511 USA
[3] Yale Univ, Sch Med, Dept Pharm, New Haven, CT 06510 USA
关键词
Bayesian hierarchical model; iTRAQ; Mixed-effects model; Nonignorable missing; Protein quantitation;
D O I
10.1007/s12561-009-9013-2
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
iTRAQ (isobaric Tags for Relative and Absolute Quantitation) is a technique that allows simultaneous quantitation of proteins in multiple samples. In this paper, we describe a Bayesian hierarchical model-based method to infer the relative protein expression levels and hence to identify differentially expressed proteins from iTRAQ data. Our model assumes that the measured peptide intensities are affected by both protein expression levels and peptide specific effects. The values of these two effects across experiments are modeled as random effects. The nonrandom missingness of peptide data is modeled with a logistic regression which relates the missingness probability for a peptide with the expression level of the protein that produces this peptide. We propose a Markov chain Monte Carlo method for the inference of model parameters, including the relative expression levels across samples. Our simulation results suggest that the estimates of relative protein expression levels based on the MCMC samples have smaller bias than those estimated from ANOVA models or fold changes. We apply our method to an iTRAQ dataset studying the roles of Caveolae for postnatal cardiovascular function.
引用
收藏
页码:228 / 245
页数:18
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