SpliceWiz: interactive analysis and visualization of alternative splicing in R

Abstract

Alternative splicing (AS) is a crucial mechanism for regulating gene expression and isoform diversity in eukaryotes. However, the analysis and visualization of AS events from RNA sequencing data remains challenging. Most tools require a certain level of computer literacy and the available means of visualizing AS events, such as coverage and sashimi plots, have limitations and can be misleading. To address these issues, we present SpliceWiz, an R package with an interactive Shiny interface that allows easy and efficient AS analysis and visualization at scale. A novel normalization algorithm is implemented to aggregate splicing levels within sample groups, thereby allowing group differences in splicing levels to be accurately visualized. The tool also offers downstream gene ontology enrichment analysis, highlighting ASEs belonging to functional pathways of interest. SpliceWiz is optimized for speed and efficiency and introduces a new file format for coverage data storage that is more efficient than BigWig. Alignment files are processed orders of magnitude faster than other R-based AS analysis tools and on par with command-line tools. Overall, SpliceWiz streamlines AS analysis, enabling reliable identification of functionally relevant AS events for further characterization. SpliceWiz is a Bioconductor package and is also available on GitHub (https://github.com/alexchwong/SpliceWiz).

Transcriptomic evaluation of tau and TDP-43 synergism shows tauopathy predominance and reveals potential modulating targets

“…TDP-43 is a major mRNA splicing regulator, and changes in splicing are found in TDP-43 proteinopathies including ALS, FTLD-TDP, and LATE ( Chang et al, 2023 ; Chung et al, 2024 ; Mehta et al, 2023 ). We evaluated transcriptomic data from tau Tg, TDP-43 Tg, and tau-TDP-43 Tg animals for alternative splicing using established analysis methods (DEXSeq and SpliceWiz) ( Anders et al, 2012 ; Wong et al, 2024 ). While differential gene expression may correspond with changes in total protein levels, differential exon usage can lead to alterations in protein isoform abundance.…”

Control of 3’ splice site selection by the yeast splicing factor Fyv6

“…Canonical branch points were used as defined in the Ares Intron Database (Grate and Ares, 2002). Differential splicing analysis was conducted with SpliceWiz (Wong et al, 2024).…”