SRCP: a comprehensive pipeline for accurate annotation and quantification of circRNAs

Area of Science:

• Bioinformatics
• Genomics
• Molecular Biology

Background:

• Circular RNAs (circRNAs) are a class of non-coding RNAs with emerging roles in gene regulation.
• Accurate annotation and quantification of circRNAs are crucial for understanding their functions.
• Existing computational pipelines have limitations in sensitivity and comprehensiveness.

Purpose of the Study:

• To introduce a novel integrative approach, the Short Read circRNA Pipeline (SRCP), for accurate circRNA annotation and quantification.
• To demonstrate the superior performance of SRCP compared to individual pipelines.
• To facilitate circRNA research by providing a validated circRNA collection.

Main Methods:

• SRCP employs a two-step strategy: annotation of validated circRNAs followed by quantification.
• A comprehensive collection of validated circRNAs was generated for five organisms, including humans.
• The pipeline was applied to identify circRNAs bound to AGO2 in human brain samples.

Main Results:

• SRCP exhibits higher sensitivity and more comprehensive quantification of circRNAs compared to other pipelines.
• A larger number of differentially expressed circRNAs were identified using SRCP.
• A subset of circRNAs bound to the miRNA-effector protein AGO2 was identified in human brain samples.

Conclusions:

• SRCP provides a more sensitive and comprehensive approach for circRNA analysis.
• The validated circRNA collection facilitates cross-species circRNA research.
• The identification of AGO2-bound circRNAs offers insights into circRNA regulatory mechanisms.