KnockRBP: an integrated multi-omics database of functional perturbation profiles for RNA-binding proteins

Area of Science:

• Genomics and Molecular Biology
• Bioinformatics and Computational Biology

Background:

• RNA-binding proteins (RBPs) control crucial post-transcriptional gene regulation, but their comprehensive functional impacts are not fully understood.
• Investigating RBP functions requires integrating data across multiple molecular levels.

Purpose of the Study:

• To develop KnockRBP, a comprehensive multi-omics database detailing regulatory changes from genetic RBP perturbations.
• To provide a resource for exploring RBP-mediated post-transcriptional regulation and its link to human diseases.

Main Methods:

• Integrated 1453 datasets (RNA-seq, Ribo-seq, miRNA-seq, 3'RACE-seq) from public repositories (GEO, ENA, ENCORE).
• Covered 639 RBPs, 182 cell lines, and 61 diseases, analyzing alternative splicing, polyadenylation, RNA editing, transcript abundance, translation efficiency, and miRNA expression.
• Standardized analytical pipelines were used for annotation, including ORF consequences, predicted loss-of-function, and disease/drug associations.

Main Results:

• KnockRBP systematically catalogs multi-omics data linked to RBP perturbations.
• The database enables exploration of RBP-specific regulatory events and their consequences across molecular layers.
• Integrated analytical modules facilitate prioritization of regulatory events and inference of cross-layer regulatory mechanisms.

Conclusions:

• KnockRBP offers a unique resource by integrating multi-omics data with perturbation-aware functional annotation for RBPs.
• It facilitates mechanistic investigations into post-transcriptional regulation and the identification of RBP-affected genes and events.
• This freely accessible database serves as a community resource to advance RBP functional genomics and disease research.