CADRES: An Analytical Pipeline for Precise Identification of Differential RNA Editing Events Across Varied Biological Conditions

RNA editing is a post-transcriptional modification critical for gene regulation and adaptation. Detecting these modifications, especially Differential Variants on RNA (DVRs), presents significant challenges due to the subtlety of RNA editing sites and the complexity of RNA sequences. To improve the detection and analysis of RNA editing sites, we developed the Calibrated Differential RNA Editing Scanner (CADRES), an analytical pipeline that combines sophisticated DNA/RNA variant calling with detailed statistical analysis. This study validates CADRES through rigorous in silico and experimental dataset using inducible cell models of the APOBEC3B (A3B) deaminase. CADRES demonstrates improved specificity and accuracy over existing methodologies, effectively identifying A3B-mediated C > U edits and distinguishing these from related sequencing artifacts and DNA polymorphisms. The adaptability of CADRES is highlighted by its consistent performance across varied experimental conditions and different numbers of replicates. Our findings illustrate that CADRES provides a reliable tool for the precise identification of RNA editing sites, contributing valuable insights into RNA editing dynamics. This capability is crucial for advancing our understanding of the molecular mechanisms underlying gene expression regulation and the potential development of therapeutic strategies.