OncoSplicing 3.0: an updated database for identifying RBPs regulating alternative splicing events in cancers
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Published on: December 9, 2016
Yangjun Zhang1,2,3,4, Kai Liu3, Zhenzhen Xu3
1Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital, Wuhan University, Wuhan 430000, China.
Abstract:
Alternative splicing (AS) is a crucial mechanism to regulate gene expression and protein complexity. RNA-binding proteins (RBPs) play an important role in regulating abnormal alternative splicing in cancers. However, few resources are available to identify specific RBPs responsible for regulating individual AS event. We have developed the OncoSplicing database for integrative analysis of clinically relevant alternative splicing events in TCGA cancers. Here, we further updated the OncoSplicing database by performing correlation analysis between the splicing and mRNA expression data from the TCGA cancers or GTEx tissues, mapping known RNA-binding motifs and eCLIP-seq peaks to all AS events, conducting splicing analysis for RNA-seq data from RBP perturbation experiments in the ENCODE project, and integrating exon and intron sequences for each AS event. With this updated database, users can easily identify potential RBPs responsible for the queried AS event and obtain sequences to design AS-specific primers and minigene constructs for experiment validation. Overall, compared to the previous version, the substantially updated OncoSplicing database (www.oncosplicing.com) offers a more valuable resource for users to identify RBPs responsible for regulating alternative splicing events in cancers.
Insights
The updated OncoSplicing database helps identify RNA-binding proteins (RBPs) that regulate alternative splicing (AS) in cancer. This resource aids researchers in understanding cancer-specific AS events and validating potential RBP targets.
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.
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