SplicingFactory-splicing diversity analysis for transcriptome data

Area of Science:

• Molecular Biology
• Bioinformatics
• Genomics

Background:

• Alternative splicing generates diverse RNA molecules, crucial for biological complexity.
• Existing methods focus on coordinated isoform expression changes, potentially missing stochastic variations.
• Understanding RNA isoform diversity is vital for interpreting biological states and disease mechanisms.

Purpose of the Study:

• To develop a computational tool for characterizing and analyzing RNA isoform diversity.
• To assess the impact of various factors on isoform diversity calculations.
• To identify genes with altered isoform diversity associated with specific mutations.

Main Methods:

• Development of the SplicingFactory R package for calculating RNA isoform diversity metrics.
• Comparative analysis of different RNA-sequencing quantification tools and their impact on diversity metrics.
• Application of the package to analyze isoform diversity in hematopoietic stem cells and myelodysplastic syndrome samples.

Main Results:

• SplicingFactory quantifies and compares RNA isoform diversity across conditions.
• The study evaluated the influence of quantification tools, expression levels, and isoform number on diversity metrics.
• A subset of genes exhibiting altered isoform diversity associated with SF3B1 mutations was identified in myelodysplastic syndrome samples.

Conclusions:

• SplicingFactory provides a novel approach to analyze RNA isoform diversity beyond simple expression level changes.
• The findings highlight the association between altered isoform diversity and SF3B1 mutations in myelodysplastic syndrome.
• The package facilitates deeper insights into the functional consequences of alternative splicing variations.