Adenosine-to-Inosine (A-to-I) RNA editing is the most prevalent post-transcriptional modification of RNA molecules. Researchers have attempted to find reliable RNA editing using next generation sequencing (NGS) data. However, most of these attempts suffered from a high rate of false positives, and they did not consider the clinical relevance of the identified RNA editing, for example, in disease progression.
Researchers at Seoul National University devised an effective RNA-editing discovery pipeline called CREDO, which includes novel statistical filtering modules based on integration of DNA- and RNA-seq data from matched tumor-normal tissues. CREDO was compared with three other RNA-editing discovery pipelines and found to give significantly fewer false positives. Application of CREDO to breast cancer data from the Cancer Genome Atlas (TCGA) project discovered highly confident RNA editing with clinical relevance to cancer progression in terms of patient survival. RNA-editing detection using DNA- and RNA-seq data from matched tumor-normal tissues should be more routinely performed as multiple omics data are becoming commonly available from each patient sample. The researchers believe CREDO is an effective and reliable tool for this problem.
(A) CREDO RNA-Editing discovery pipeline. Novel statistical RNA-editing discovery modules are colored in dark blue. Scatter plots show A-to-G loci before and after the statistical discovery filter application. (B) Number of editing sites discovered by CREDO. Zero-confidence score ≥ 10.0 (C) Number of editing sites identified in more than 4 individuals out of the loci in (B).