Human Splicing Finder

Human Splicing Finder predicts and analyzes the impact of mutations on mRNA splicing signals and motifs in human genes to assess effects on splicing regulation.

Key Features:

• Algorithm integration: Combines 12 distinct algorithms to identify and assess mutations affecting splicing.
• Splice-site and branch-point analysis: Detects and evaluates acceptor and donor splice sites and branch points.
• Auxiliary motif analysis: Predicts Exonic Splicing Enhancers (ESE) and Exonic Splicing Silencers (ESS) using Position Weight Matrices (PWMs).
• Protein-specific PWMs: Includes PWMs for binding sites of proteins such as 9G8, Tra2-beta Serine-Arginine, and hnRNP A1.
• Mutation types covered: Assesses effects of synonymous, non-synonymous, and nonsense mutations on splicing.
• Sequence scope: Analyzes splicing signals and motifs within any human sequence.
• Performance validation: Evaluated on a dataset of 83 intronic and 35 exonic mutations known to cause splicing defects with accurate predictions in nearly all cases.

Scientific Applications:

• Diagnostic assessments: Interprets the splicing impact of genetic variants for diagnostic evaluation.
• Therapeutic intervention design: Supports design and evaluation of exon skipping strategies by predicting mutation-induced splicing alterations.
• Genomic project support: Provides splicing variation analyses for large-scale studies such as the GEN2PHEN European Project and the Human Variome Project.
• Mechanistic studies: Offers insights into mechanisms underlying mRNA splicing and mutation-associated splicing defects.

Methodology:

Integrates 12 distinct algorithms to identify and assess effects of mutations on acceptor and donor splice sites, branch points, and auxiliary motifs using Position Weight Matrices (PWMs) for auxiliary sequence prediction, and was validated on a dataset of 83 intronic and 35 exonic splicing-defect mutations.