IsoDOT – Differential RNA-isoform Expression

Researchers at UNC Chapel Hill 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. The researchers 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.

rna-seq

(a) IsoDOT work flow. The dash line indicates that known isoform annotation (i.e., transcriptome annotation) is optional, (b) A gene with 3 exons and 3 possible isoforms. (c) A matrix of input data. Each row corresponding to an exon set. The column “Count” is the number of RNA-seq fragments at each exon set, and the columns “isoform k” for k = 1,2,3 give the effective lengths of each exon set within each isoform, and specifically, ηA,k is the effective length of exon set A for the k-th isoform. NB(μ,φ) indicates a negative binomial distribution with mean μ, and dispersion parameter φ.

Availability – An R package of IsoDOT is available at http://www.bios.unc.edu/∼weisun/software/isoform.htm.

Sun W, Liu Y, Crowley JJ, Chen TH, Zhou H, Chu H, Huang S, Kuan PF, Li Y, Miller DR, Shaw GD, Wu Y, Zhabotynsky V, McMillan L, Zou F, Sullivan PF, de Villena FP. (2015) IsoDOT Detects Differential RNA-isoform Expression/Usage with respect to a Categorical or Continuous Covariate with High Sensitivity and Specificity. J Am Stat Assoc 110(511):975-986. [article]

 

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