title: IsoDOT Detects Differential RNA-isoform Expression/Usage with respect to a Categorical or Continuous Covariate with High Sensitivity and Specificity.
abstract: We have developed a statistical method named IsoDOT to assess differential isoform expression (DIE) and differential isoform usage (DIU) using RNA-seq data. Here isoform usage refers to relative isoform expression given the total expression of the corresponding gene. IsoDOT performs two tasks that cannot be accomplished by existing methods: to test DIE/DIU with respect to a continuous covariate, and to test DIE/DIU for one case versus one control. The latter task is not an uncommon situation in practice, e.g., comparing the paternal and maternal alleles of one individual or comparing tumor and normal samples of one cancer patient. Simulation studies demonstrate the high sensitivity and specificity of IsoDOT. We apply IsoDOT to study the effects of haloperidol treatment on the mouse transcriptome and identify a group of genes whose isoform usages respond to haloperidol treatment.
authors.affiliation: Department of Biostatistics, Department of Genetics, UNC Chapel Hill, NC 27599.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Statistics and Operations Research, Department of Genetics, Department and Biostatistics, UNC Chapel Hill.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Genetics, UNC Chapel Hill.
authors.forename: James J
authors.initials: JJ
authors.lastname: Crowley
authors.affiliation: National Cancer Institute.
authors.forename: Ting-Hued
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Department of Statistics, NC State University.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Biostatistics, University of Minnesota.
authors.forename: Haitao
authors.initials: H
authors.lastname: Chu
authors.affiliation: SAS Institute Inc.
authors.forename: Shunping
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University.
authors.forename: Pei-Fen
authors.initials: PF
authors.lastname: Kuan
authors.affiliation: Department of Statistics, NC State University.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Genetics, Lineberger Comprehensive Cancer Center, UNC Chapel Hill.
authors.forename: Darla R
authors.initials: DR
authors.lastname: Miller
authors.affiliation: Department of Genetics, Lineberger Comprehensive Cancer Center, UNC Chapel Hill.
authors.forename: Ginger D
authors.initials: GD
authors.lastname: Shaw
authors.affiliation: Department of Statistics, NC State University.
authors.forename: Yichao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Biostatistics, UNC Chapel Hill.
authors.forename: Vasyl
authors.initials: V
authors.lastname: Zhabotynsky
authors.affiliation: Department of Computer Science, UNC Chapel Hill.
authors.forename: Leonard
authors.initials: L
authors.lastname: McMillan
authors.affiliation: Department of Biostatistics, UNC Chapel Hill.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.affiliation: Department of Genetics, Department of Psychiatry, Department of Epidemiology, UNC Chapel Hill.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
authors.affiliation: Department of Genetics, UNC Chapel Hill.
authors.forename: Fernando Pardo-Manuel
authors.initials: FP
authors.lastname: de Villena
keywords: RNA-seq; differential isoform expression; differential isoform usage; isoform; penalized regression