SpliceVista, a tool for splice variant identification and visualization in shotgun proteomics data

Area of Science:

• Proteomics
• Bioinformatics
• Molecular Biology

Background:

• Alternative splicing is a key regulatory process in eukaryotes, producing diverse protein isoforms.
• Aberrant alternative splicing is linked to numerous human diseases.
• Existing methods primarily analyze splice variants at the RNA level, lacking protein-level insights.

Purpose of the Study:

• To introduce SpliceVista, a novel computational tool for identifying and visualizing protein splice variants.
• To enable the analysis of splice variants directly from mass spectrometry proteomics data.
• To facilitate the detection of splice variant-specific peptides for targeted analysis.

Main Methods:

• SpliceVista integrates gene structure and translated sequences from alternative splicing databases.
• It maps mass spectrometry-identified peptides to potential splice variants.
• The tool visualizes splice variant exon composition and peptide alignments, with options for quantitative analysis.

Main Results:

• SpliceVista successfully identified thousands of splice-variant-specific peptides and hundreds of splice variants in experimental datasets.
• Differential regulation of splice variants was detected after drug treatment (gefitinib) and in different cell types.
• The tool demonstrated the ability to visualize novel splice variants supported by peptide evidence.

Conclusions:

• SpliceVista provides a powerful platform for the visualization, detection, and differential quantification of protein splice variants.
• It addresses a critical gap in current proteomics analysis by enabling protein-level splice variant investigation.
• This approach can reveal disease-associated splice variants and provide deeper biological insights often missed by RNA-centric methods.