ASCOT identifies key regulators of neuronal subtype-specific splicing

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Publicly available next-generation sequencing data is underutilized due to analysis challenges.
• Understanding cell type-specific RNA splicing is crucial for biological insights.

Purpose of the Study:

• To present ASCOT, a novel resource for rapid analysis and visualization of splice variants.
• To demonstrate ASCOT's utility in identifying cell type-specific alternative exons and studying photoreceptor splicing.

Main Methods:

• Developed ASCOT, employing annotation-free methods for splice variant analysis.
• Analyzed tens of thousands of bulk and single-cell RNA sequencing datasets.
• Leveraged ENCODE and GTEx data to investigate photoreceptor splicing.

Main Results:

• Identified novel cell type-specific alternative exons in the nervous system.
• Characterized unique splicing patterns in photoreceptors using public data.
• Demonstrated that PTBP1 knockdown and specific protein overexpression can activate photoreceptor-specific exons in liver cells.

Conclusions:

• ASCOT facilitates large-scale analysis of public RNA-Seq data for novel biological discoveries.
• Highlights the importance of considering both annotated and unannotated splicing events for understanding gene regulation.
• Provides insights into cell type-specific control of RNA splicing.