IUTA

IUTA detects differential isoform usage in RNA-Seq data to characterize alternative splicing at the transcript level.

Key Features:

• Comprehensive isoform testing: Tests each gene genome-wide for differential isoform usage between two groups of samples.
• Isoform fraction assessment: Assesses differences in the fraction of total expression represented by each isoform within a gene.
• Statistical framework (Aitchison geometry): Formulates the testing problem as evaluation of equal means for two probability distributions under Aitchison geometry for compositional data.
• Performance versus Cuffdiff2: On simulated data, provides test results for substantially more genes and shows superior detection where both methods report results compared to Cuffdiff2 (version 2.2.0).
• Application to real RNA-Seq data: Identified 2,073 significant genes with differential isoform usage when applied to mouse RNA-Seq datasets from six tissues.
• Implementation: Implemented as an R package.

Scientific Applications:

• Alternative splicing studies: Characterizes transcript-level changes driven by alternative splicing across conditions or tissues.
• Isoform-specific expression analysis: Enables analysis of isoform-level expression patterns to investigate regulation at the transcript level.
• Development and disease research: Supports investigation of roles of alternative transcripts in cell development and disease contexts.
• Large-scale RNA-Seq analyses: Applicable to large RNA-Seq datasets for genome-wide isoform usage profiling.

Methodology:

Represents isoform expression as compositional vectors of isoform fractions per gene, performs per-gene differential testing between two groups by evaluating equal means for two probability distributions under Aitchison geometry, implemented in R.