A Markov random field-based approach for joint estimation of differentially expressed genes in mouse transcriptome data

• Published in: Statistical applications in genetics and molecular biology Vol. 15; no. 2; pp. 139 - 150
• Main Authors: Lin, Zhixiang, Li, Mingfeng, Sestan, Nenad, Zhao, Hongyu
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 01.04.2016
• Subjects: Animals; Computer Simulation; Female; Gene Expression Profiling - statistics & numerical data; High-Throughput Nucleotide Sequencing - statistics & numerical data; Male; Markov Chains; Markov random field model; Mice; Models, Statistical; neurodevelopment; Regression Analysis; RNA-Seq and differential expression; Sequence Analysis, RNA - methods; Sequence Analysis, RNA - statistics & numerical data; Transcriptome - genetics
• ISSN: 2194-6302; 1544-6115
• DOI: 10.1515/sagmb-2015-0070

The statistical methodology developed in this study was motivated by our interest in studying neurodevelopment using the mouse brain RNA-Seq data set, where gene expression levels were measured in multiple layers in the somatosensory cortex across time in both female and male samples. We aim to identify differentially expressed genes between adjacent time points, which may provide insights on the dynamics of brain development. Because of the extremely small sample size (one male and female at each time point), simple marginal analysis may be underpowered. We propose a Markov random field (MRF)-based approach to capitalizing on the between layers similarity, temporal dependency and the similarity between sex. The model parameters are estimated by an efficient EM algorithm with mean field-like approximation. Simulation results and real data analysis suggest that the proposed model improves the power to detect differentially expressed genes than simple marginal analysis. Our method also reveals biologically interesting results in the mouse brain RNA-Seq data set.