OncoSplicing 3.0: an updated database for identifying RBPs regulating alternative splicing events in cancers

Area of Science:

• Molecular Biology
• Genomics
• Bioinformatics

Background:

• Alternative splicing (AS) is a key regulator of gene expression and protein diversity.
• RNA-binding proteins (RBPs) are implicated in aberrant AS in cancer, but resources for identifying specific RBPs are limited.
• The OncoSplicing database was initially developed for analyzing TCGA cancer splicing events.

Purpose of the Study:

• To enhance the OncoSplicing database as a comprehensive resource for identifying RBPs regulating specific AS events in cancer.
• To provide tools for experimental validation of AS events and their regulatory RBPs.

Main Methods:

• Integrated TCGA and GTEx splicing and mRNA expression data.
• Mapped RNA-binding motifs and eCLIP-seq peaks to AS events.
• Analyzed RNA-seq data from RBP perturbation experiments (ENCODE).
• Incorporated exon and intron sequences for each AS event.

Main Results:

• The updated OncoSplicing database links AS events to potential regulatory RBPs.
• Users can identify candidate RBPs for specific AS events.
• Sequences for designing validation constructs (primers, minigenes) are available.

Conclusions:

• The substantially updated OncoSplicing database (www.oncosplicing.com) is a valuable resource for cancer research.
• Facilitates the identification of RBPs driving cancer-specific alternative splicing.
• Supports experimental validation of AS regulatory mechanisms in cancer.