Extending scope and power of circular RNA research with circtools 2.0

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Circular RNAs (circRNAs) are key gene regulators with cell-specific expression.
• Detecting circRNAs from RNA-sequencing data is challenging due to the need for specialized back-splice junction identification.
• Previous development of circtools provided a foundational tool for circRNA analysis.

Purpose of the Study:

• Introduce circtools 2.0, an advanced framework for computational and experimental circRNA research.
• Enhance circRNA detection accuracy and expand analytical capabilities.
• Facilitate integration with emerging technologies like spatial transcriptomics and long-read sequencing.

Main Methods:

• Implemented an ensemble approach for circRNA detection to improve recall rates.
• Developed a module for automated circRNA padlock probe design for Xenium spatial transcriptomics.
• Integrated circRNA conservation analysis across animal models.
• Added support for Oxford Nanopore sequencing for full-length circRNA detection.

Main Results:

• Circtools 2.0 offers improved circRNA detection recall.
• Automated probe design facilitates spatial circRNA analysis.
• Conservation analysis provides insights into evolutionary roles.
• Long-read sequencing support enables comprehensive circRNA profiling.

Conclusions:

• Circtools 2.0 significantly advances computational and experimental circRNA research.
• The enhanced framework supports diverse applications from basic research to translational studies.
• This toolset empowers researchers with novel capabilities for circRNA investigation.