title: Conditional estimation of local pooled dispersion parameter in small-sample RNA-Seq data improves differential expression test.
abstract: High throughput sequencing technology in transcriptomics studies contribute to the understanding of gene regulation mechanism and its cellular function, but also increases a need for accurate statistical methods to assess quantitative differences between experiments. Many methods have been developed to account for the specifics of count data: non-normality, a dependence of the variance on the mean, and small sample size. Among them, the small number of samples in typical experiments is still a challenge. Here we present a method for differential analysis of count data, using conditional estimation of local pooled dispersion parameters. A comprehensive evaluation of our proposed method in the aspect of differential gene expression analysis using both simulated and real data sets shows that the proposed method is more powerful than other existing methods while controlling the false discovery rates. By introducing conditional estimation of local pooled dispersion parameters, we successfully overcome the limitation of small power and enable a powerful quantitative analysis focused on differential expression test with the small number of samples.
authors: * Institute of Health and Environment, Seoul National University, Gwanak-gu Seoul, 151-747, South Korea.
authors: Jungsoo
authors: J
authors: Gim
authors: † Graduate School of Public Health, Seoul National University, Gwanak-gu Seoul, 151-747, South Korea.
authors: Sungho
authors: S
authors: Won
authors: ‡ Department of Statistics, Seoul National University, Gwanak-gu Seoul, 151-747, South Korea.
authors: Taesung
authors: T
authors: Park
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D030541:Databases, Genetic; D005260:Female; D005786:Gene Expression Regulation; D060148:HapMap Project; D006801:Humans; D008297:Male; D008957:Models, Genetic; D018401:Sample Size; D017423:Sequence Analysis, RNA / Q000379:methods* / Q000706:statistics & numerical data
keywords: Differential expression test; RNA-Seq analysis; local pooled dispersion estimation; small sample data