EasyCircR:Detection and reconstruction of circular RNAs post-transcriptional regulatory interaction networks

Abstract

Circular RNAs (circRNAs) are regulatory RNAs that play a crucial role in various biological activities and have been identified as potential biomarkers for the development of neurological disorders and cancer. CircRNAs have emerged as significant regulators of gene expression through different mechanisms, including regulation of transcription and splicing, modulation of translation, and post-translational modification. Additionally, some circRNAs function as microRNA (miRNA) sponges in the cytoplasm, enhancing the expression of target genes by suppressing miRNA activity. Although existing pipelines reconstruct circRNAs, identify miRNAs sponged by them, retrieve cascade-regulated mRNAs, and represent the regulatory interactions as complex circRNA-miRNA-mRNA networks, none of the state-of-the-art approaches can discriminate the biological level at which the mRNAs involved in the interactions are regulated. EasyCircR is a novel R package that combines circRNA detection and reconstruction with post-transcriptional gene expression analysis (exon-intron split analysis) and miRNA response element prediction. The package enables estimation and visualization of circRNA-miRNA-mRNA interactions through an intuitive Shiny application, taking advantage of the post-transcriptional regulatory nature of circRNAs and excluding unrealistic regulatory outcomes. EasyCircR source code, Docker container and user guide are available at: https://github.com/InfOmics/EasyCircR