OncoSplicing: an updated database for clinically relevant alternative splicing in 33 human cancers

Area of Science:

• Molecular Biology
• Genomics
• Bioinformatics

Background:

• Alternative splicing (AS) is a key post-transcriptional mechanism regulating gene expression and protein diversity.
• Aberrant splicing patterns are implicated in the development and progression of various cancers.
• The OncoSplicing database was initially developed to visualize survival-associated and differential AS events in cancer.

Purpose of the Study:

• To present a substantially updated version of the OncoSplicing database.
• To provide an integrated, user-friendly platform for exploring clinically relevant alternative splicing events across a wide range of cancers.
• To enhance the utility of the database with new features for survival analysis, differential analysis, and identification of cancer-specific splicing events.

Main Methods:

• Integration of large-scale alternative splicing data from TCGA SpliceSeq (122,423 events, 33 cancers) and TCGA SplAdder (238,558 events, 32 cancers).
• Development of features for survival analysis using median and optimal cut-offs.
• Implementation of differential analysis comparing tumor samples with normal samples (TCGA and GTEx).
• Inclusion of pan-cancer views, Cox'PH regression results, and identification of clinical indicator-relevant splicing events.
• Annotation of AS-associated transcripts and provision of downloadable splicing data from the SplAdder project.

Main Results:

• The updated OncoSplicing database provides comprehensive data on 122,423 AS events (TCGA SpliceSeq) and 238,558 AS events (TCGA SplAdder) across 33 and 32 cancer types, respectively.
• New features enable detailed survival analysis, differential splicing analysis against normal tissues, and identification of cancer-specific splicing events.
• The database facilitates the discovery of clinically relevant splicing events and their association with patient outcomes.
• Pan-cancer views and Cox'PH regression results offer a broader perspective on splicing alterations in cancer.

Conclusions:

• The updated OncoSplicing database serves as a valuable, user-friendly, and registration-free resource for researchers studying clinically relevant alternative splicing in human cancers.
• It facilitates the exploration of AS events associated with patient survival and cancer-specific alterations.
• The integrated data and enhanced features support the investigation of the role of alternative splicing in cancer etiology and progression.