A Bayesian mixture model for differential gene expression

被引:108
作者
Do, KA [1 ]
Müller, P [1 ]
Tang, F [1 ]
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA
关键词
density estimation; Dirichlet process; gene expression; microarrays; mixture models; nonparametric Bayes method;
D O I
10.1111/j.1467-9876.2005.05593.x
中图分类号
O21 [概率论与数理统计]; C8 [统计学];
学科分类号
020208 ; 070103 ; 0714 ;
摘要
We propose model-based inference for differential gene expression, using a nonparametric Bayesian probability model for the distribution of gene intensities under various conditions. The probability model is a mixture of normal distributions. The resulting inference is similar to a popular empirical Bayes approach that is used for the same inference problem. The use of fully model-based inference mitigates some of the necessary limitations of the empirical Bayes method. We argue that inference is no more difficult than posterior simulation in traditional nonparametric mixture-of-normal models. The approach proposed is motivated by a microarray experiment that was carried out to identify genes that are differentially expressed between normal tissue and colon cancer tissue samples. Additionally, we carried out a small simulation study to verify the methods proposed. In the motivating case-studies we show how the nonparametric Bayes approach facilitates the evaluation of posterior expected false discovery rates. We also show how inference can proceed even in the absence of a null sample of known non-differentially expressed scores. This highlights the difference from alternative empirical Bayes approaches that are based on plug-in estimates.
引用
收藏
页码:627 / 644
页数:18
相关论文
共 39 条
[1]   Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays [J].
Alon, U ;
Barkai, N ;
Notterman, DA ;
Gish, K ;
Ybarra, S ;
Mack, D ;
Levine, AJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (12) :6745-6750
[2]   MIXTURES OF DIRICHLET PROCESSES WITH APPLICATIONS TO BAYESIAN NONPARAMETRIC PROBLEMS [J].
ANTONIAK, CE .
ANNALS OF STATISTICS, 1974, 2 (06) :1152-1174
[3]   Identifying differentially expressed genes in cDNA microarray experiments [J].
Baggerly, KA ;
Coombes, KR ;
Hess, KR ;
Stivers, DN ;
Abruzzo, LV ;
Zhang, W .
JOURNAL OF COMPUTATIONAL BIOLOGY, 2001, 8 (06) :639-659
[4]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[5]   Rao-Blackwellisation of sampling schemes [J].
Casella, G ;
Robert, CP .
BIOMETRIKA, 1996, 83 (01) :81-94
[6]  
CHEN M, 2004, CLASS NEW MIXTURE MO
[7]  
Chen Y, 1997, J Biomed Opt, V2, P364, DOI 10.1117/12.281504
[8]   An ANOVA model for dependent random measures [J].
De Iorio, M ;
Müller, P ;
Rosner, GL ;
MacEachern, SN .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 2004, 99 (465) :205-215
[9]   Empirical Bayes analysis of a microarray experiment [J].
Efron, B ;
Tibshirani, R ;
Storey, JD ;
Tusher, V .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 2001, 96 (456) :1151-1160
[10]  
Escobar M., 1988, THESIS YALE U NEW HA