A Bayesian mixture model for differential gene expression

被引:107
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
[31]  
SMYTH GK, 2002, FUNCTIONAL GENOMICS
[32]  
Storey J. D., 2003, ANAL GENE EXPRESSION
[33]   A direct approach to false discovery rates [J].
Storey, JD .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 2002, 64 :479-498
[34]  
TIERNEY L, 1994, ANN STAT, V22, P1701, DOI 10.1214/aos/1176325750
[35]   Significance analysis of microarrays applied to the ionizing radiation response [J].
Tusher, VG ;
Tibshirani, R ;
Chu, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (09) :5116-5121
[36]   Bayesian nonparametric inference for random distributions and related functions [J].
Walker, SG ;
Damien, P ;
Laud, PW ;
Smith, AFM .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1999, 61 :485-527
[37]  
Wu TD, 2001, J PATHOL, V195, P53, DOI 10.1002/1096-9896(200109)195:1<53::AID-PATH891>3.0.CO
[38]  
2-H
[39]  
Yang YH, 2001, PROC SPIE, V4266, P141, DOI 10.1117/12.427982