A Joint Bayesian Model for Integrating Microarray and RNA Sequencing Transcriptomic Data

被引:21
作者
Ma, Tianzhou [1 ]
Liang, Faming [2 ]
Oesterreich, Steffi [3 ,4 ]
Tseng, George C. [1 ,5 ,6 ]
机构
[1] Univ Pittsburgh, Dept Biostat, 130 Desoto St, Pittsburgh, PA 15261 USA
[2] Univ Florida, Dept Biostat, Gainesville, FL USA
[3] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA
[4] Womens Canc Res Ctr, Pittsburgh, PA USA
[5] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA
[6] Univ Pittsburgh, Dept Computat Biol, Pittsburgh, PA USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
Bayesian hierarchical model; differential expression (DE); meta-analysis; microarray; normalization; RNA sequencing (RNA-seq); DIFFERENTIAL GENE-EXPRESSION; SEQ; REPRODUCIBILITY; BIAS;
D O I
10.1089/cmb.2017.0056
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
As the sequencing cost continued to drop in the past decade, RNA sequencing (RNA-seq) has replaced microarray to become the standard high-throughput experimental tool to analyze transcriptomic profile. As more and more datasets are generated and accumulated in the public domain, meta-analysis to combine multiple transcriptomic studies to increase statistical power has received increasing popularity. In this article, we propose a Bayesian hierarchical model to jointly integrate microarray and RNA-seq studies. Since systematic fold change differences across RNA-seq and microarray for detecting differentially expressed genes have been previously reported, we replicated this finding in several real datasets and showed that incorporation of a normalization procedure to account for the bias improves the detection accuracy and power. We compared our method with the popular two-stage Fisher's method using simulations and two real applications in a histological subtype (invasive lobular carcinoma) of breast cancer comparing PR+ versus PR- and early-stage versus late-stage patients. The result showed improved detection power and more significant and interpretable pathways enriched in the detected biomarkers from the proposed Bayesian model.
引用
收藏
页码:647 / 662
页数:16
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