title: A powerful statistical approach for large-scale differential transcription analysis.
abstract: Next generation sequencing (NGS) is increasingly being used for transcriptome-wide analysis of differential gene expression. The NGS data are multidimensional count data. Therefore, most of the statistical methods developed well for microarray data analysis are not applicable to transcriptomic data. For this reason, a variety of new statistical methods based on count data of transcript reads have been correspondingly proposed. But due to high cost and limitation of biological resources, current NGS data are still generated from a few replicate libraries. Some of these existing methods do not always have desirable performances on count data. We here developed a very powerful and robust statistical method based on beta and binomial distributions. Our method (mBeta t-test) is specifically applicable to sequence count data from small samples. Both simulated and real transcriptomic data showed mBeta t-test significantly outperformed the existing top statistical methods chosen in all 12 given scenarios and performed with high efficiency and high stability. The differentially expressed genes found by our method from real transcriptomic data were validated by qPCR experiments. Our method shows high power in finding truly differential expression, conservatively estimating FDR and high stability in RNA sequence count data derived from small samples. Our method can also be extended to genome-wide detection of differential splicing events.
authors.affiliation: Department of Molecular Physiology and Biophysics and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, 77030, United States of America.
authors.forename: Yuan-De
authors.initials: YD
authors.lastname: Tan
authors.affiliation: Department of Molecular Physiology and Biophysics and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, 77030, United States of America.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Chandler
authors.affiliation: Department of Molecular Physiology and Biophysics and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, 77030, United States of America.
authors.forename: Arindam
authors.initials: A
authors.lastname: Chaudhury
authors.affiliation: Department of Molecular Physiology and Biophysics and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, 77030, United States of America.
authors.forename: Joel R
authors.initials: JR
authors.lastname: Neilson
mesh_terms: D000818:Animals; D003198:Computer Simulation; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013223:Statistics as Topic
chemical_list: D012333:RNA, Messenger