CREDO: Highly confident disease-relevant A-to-I RNA-editing discovery in breast cancer

Area of Science:

• Molecular Biology
• Genomics
• Bioinformatics

Background:

• Adenosine-to-Inosine (A-to-I) RNA editing is the most prevalent RNA modification.
• Previous RNA editing detection methods using next-generation sequencing (NGS) data often yield high false positive rates.
• Clinical relevance of detected RNA editing events, particularly in disease progression, has been largely overlooked.

Purpose of the Study:

• To develop an effective RNA-editing discovery pipeline (CREDO) to identify reliable and clinically relevant A-to-I RNA editing events.
• To reduce false positives in RNA editing detection by integrating DNA and RNA sequencing data.
• To assess the clinical significance of RNA editing in cancer progression.

Main Methods:

• Development of the CREDO pipeline incorporating novel statistical filtering modules.
• Integration of DNA- and RNA-sequencing data from matched tumor-normal tissues.
• Comparative analysis of CREDO against three existing RNA-editing discovery pipelines.
• Application of CREDO to breast cancer data from The Cancer Genome Atlas (TCGA).

Main Results:

• CREDO demonstrated significantly fewer false positives compared to other pipelines.
• CREDO identified highly confident RNA editing events in breast cancer.
• Discovered RNA editing events with significant clinical relevance to cancer progression, impacting patient survival.

Conclusions:

• CREDO is an effective and reliable tool for discovering A-to-I RNA editing.
• Integrating DNA- and RNA-seq data from matched tissues is crucial for accurate RNA editing detection.
• Routine RNA editing detection should be considered with the increasing availability of multi-omics data.