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We have developed a statistical method named IsoDOT to assess differentialisoform expression (DIE) and differential isoform usage (DIU) using RNA-seqdata. Here isoform usage refers to relative isoform expression given the totalexpression of the corresponding gene. IsoDOT performs two tasks that cannot beaccomplished by existing methods: to test DIE/DIU with respect to a continuouscovariate, and to test DIE/DIU for one case versus one control. The latter taskis not an uncommon situation in practice, e.g., comparing paternal and maternalallele of one individual or comparing tumor and normal sample of one cancerpatient. Simulation studies demonstrate the high sensitivity and specificity ofIsoDOT. We apply IsoDOT to study the effects of haloperidol treatment on mousetranscriptome and identify a group of genes whose isoform usages respond tohaloperidol treatment.

IsoDOT Detects Differential RNA-isoform Expression/Usage with respect to a Categorical or Continuous Covariate with High Sensitivity and Specificity