Subject level clustering using a negative binomial model for small transcriptomic studies

作     者：Li, Qian Noel-MacDonnell, Janelle R. Koestler, Devin C. Goode, Ellen L. Fridley, Brooke L. 

作者机构：H Lee Moffitt Canc Ctr & Res Inst Dept Biostat & Bioinformat 12902 Magnolia Dr Tampa FL 33612 USA Univ S Florida Hlth Informat Inst Tampa FL USA Childrens Mercy Hosp Kansas City MO 64108 USA Univ Kansas Med Ctr Dept Biostat Kansas City KS 66103 USA Mayo Clin Dept Hlth Sci Res Rochester MN USA 

出 版 物：《BMC BIOINFORMATICS》 (英国医学委员会:生物信息)

年 卷 期：2018年第19卷第1期

页      面：474-474页

核心收录：

学科分类：0710[理学-生物学] 0836[工学-生物工程] 10[医学] 

基　　金：University of Kansas Cancer Center [P30 CA168524] Moffitt Cancer Center 

主　　题：Negative binomial Model-based RNA-seq EM algorithm Clustering Gaussian mixture model 

摘      要：BackgroundUnsupervised clustering represents one of the most widely applied methods in analysis of high-throughput omics data. A variety of unsupervised model-based or parametric clustering methods and non-parametric clustering methods have been proposed for RNA-seq count data, most of which perform well for large samples, e.g. N500. A common issue when analyzing limited samples of RNA-seq count data is that the data follows an over-dispersed distribution, and thus a Negative Binomial likelihood model is often used. Thus, we have developed a Negative Binomial model-based (NBMB) clustering approach for application to RNA-seq *** have developed a Negative Binomial Model-Based (NBMB) method to cluster samples using a stochastic version of the expectation-maximization algorithm. A simulation study involving various scenarios was completed to compare the performance of NBMB to Gaussian model-based or Gaussian mixture modeling (GMM). NBMB was also applied for the clustering of two RNA-seq studies;type 2 diabetes study (N=96) and TCGA study of ovarian cancer (N=295). Simulation results showed that NBMB outperforms GMM applied with different transformations in majority of scenarios with limited sample size. Additionally, we found that NBMB outperformed GMM for small clusters distance regardless of sample size. Increasing total number of genes with fixed proportion of differentially expressed genes does not change the outperformance of NBMB, but improves the overall performance of GMM. Analysis of type 2 diabetes and ovarian cancer tumor data with NBMB found good agreement with the reported disease subtypes and the gene expression patterns. This method is available in an R package on CRAN named *** of Negative Binomial model based clustering is advisable when clustering over dispersed RNA-seq count data.