Modeling circRNA expression pattern with integrated sequence and epigenetic features demonstrates the potential involvement of H3K79me2 in circRNA expression

Abstract

Motivation CircRNAs are an abundant class of noncoding RNAs with widespread, cell/tissue specific patterns. Previous work suggested that epigenetic features might be related to circRNA expression. However, the contribution of epigenetic changes to circRNA expression has not been investigated systematically. Here we built a machine learning framework named CIRCScan, to predict circRNA expression in various cell lines based on the sequence and epigenetic features. Results The predicted accuracy of the expression status models was high with area under the curve of ROC (AUC) values of 0.89∼0.92 and the false positive rates (FPR) of 0.17∼0.25. Predicted expressed circRNAs were further validated by RNA-seq data. The performance of expression level prediction models was also good with normalized root-mean-square errors (RMSE) of 0.28∼0.30 and Pearson’s correlation coefficient r (PCC) over 0.4 in all cell lines, along with Spearman's correlation coefficient ρ of 0.33∼0.46. Noteworthy, H3K79me2 was highly ranked in modeling both circRNA expression status and levels across different cells. Further analysis in additional 9 cell lines demonstrated a significant enrichment of H3K79me2 in circRNA flanking intron regions, supporting the potential involvement of H3K79me2 in circRNA expression regulation. Availability The CIRCScan assembler is freely available online for academic use at https://github.com/johnlcd/CIRCScan. Supplementary information Supplementary data are available at Bioinformatics online.

Noncoding RNAs in pyroptosis and cancer progression: Effect, mechanism, and clinical application

“…CircRNAs are abundantly expressed in tumor cells and initiate the pyroptosis-related gene expression ( 62 , 63 ). On the one hand, circRNAs initiated DNA methylation of pyroptosis-associated genes ( 64 ). For example, in glioma cells, circRNA-0001836 promotes the expression of NLRP1 via DNA demethylation, leading to the activation of pyroptosis ( 30 ).…”

A Brief Review of circRNA Biogenesis, Detection, and Function

“…For example, chen et al . model circRNA expression patterns using RNA-seq data as well as integrated sequence and epigenetic features to demonstrate the potential involvement of H3K79me2 in circRNA expression [ 61 ]. Integrating sequence features with RNA sequencing data may achieve a more comprehensive understanding of circular RNA in subsequent research.…”

Machine Learning-Based Comparative Analysis of Pan-Cancer and Pan-Normal Tissues Identifies Pan-Cancer Tissue-Enriched circRNAs Related to Cancer Mutations as Potential Exosomal Biomarkers

“…The alternative splicing factor Quaking has been implicated in circRNA regulation, as it has been reported to alter circRNA expression during the epithelial-mesenchymal transition, a critical process in cancer metastasis ( 13 ). CircRNA formation is also likely associated with H3K79me2 histone modifications ( 14 ) that have been shown to regulate co-transcriptional alternative splicing ( 15 ).…”