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IsoDOT Detects Differential RNA-Isoform Expression/Usage With Respect to a Categorical or Continuous Covariate With High Sensitivity and Specificity

Author

Listed:
  • Wei Sun
  • Yufeng Liu
  • James J. Crowley
  • Ting-Huei Chen
  • Hua Zhou
  • Haitao Chu
  • Shunping Huang
  • Pei-Fen Kuan
  • Yuan Li
  • Darla Miller
  • Ginger Shaw
  • Yichao Wu
  • Vasyl Zhabotynsky
  • Leonard McMillan
  • Fei Zou
  • Patrick F. Sullivan
  • Fernando Pardo-Manuel De Villena

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, for example, 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. Supplementary materials for this article are available online.

Suggested Citation

  • Wei Sun & Yufeng Liu & James J. Crowley & Ting-Huei Chen & Hua Zhou & Haitao Chu & Shunping Huang & Pei-Fen Kuan & Yuan Li & Darla Miller & Ginger Shaw & Yichao Wu & Vasyl Zhabotynsky & Leonard McMill, 2015. "IsoDOT Detects Differential RNA-Isoform Expression/Usage With Respect to a Categorical or Continuous Covariate With High Sensitivity and Specificity," Journal of the American Statistical Association, Taylor & Francis Journals, vol. 110(511), pages 975-986, September.
    • Handle: RePEc:taf:jnlasa:v:110:y:2015:i:511:p:975-986
    DOI: 10.1080/01621459.2015.1040880
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    References listed on IDEAS

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    1. Eric T. Wang & Rickard Sandberg & Shujun Luo & Irina Khrebtukova & Lu Zhang & Christine Mayr & Stephen F. Kingsmore & Gary P. Schroth & Christopher B. Burge, 2008. "Alternative isoform regulation in human tissue transcriptomes," Nature, Nature, vol. 456(7221), pages 470-476, November.
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    1. Hillary M. Heiling & Douglas R. Wilson & Naim U. Rashid & Wei Sun & Joseph G. Ibrahim, 2023. "Estimating cell type composition using isoform expression one gene at a time," Biometrics, The International Biometric Society, vol. 79(2), pages 854-865, June.

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