Abstract

BackgroundCircular RNAs (circRNAs) play important roles in regulating gene expression through binding miRNAs and RNA binding proteins. Genetic variation of circRNAs may affect complex traits/diseases by changing their binding efficiency to target miRNAs and proteins. There is a growing demand for investigations of the functions of genetic changes using large-scale experimental evidence. However, there is no online genetic resource for circRNA genes.ResultsWe performed extensive genetic annotation of 295,526 circRNAs integrated from circBase, circNet and circRNAdb. All pre-computed genetic variants were presented at our online resource, circVAR, with data browsing and search functionality. We explored the chromosome-based distribution of circRNAs and their associated variants. We found that, based on mapping to the 1000 Genomes and ClinVAR databases, chromosome 17 has a relatively large number of circRNAs and associated common and health-related genetic variants. Following the annotation of genome wide association studies (GWAS)-based circRNA variants, we found many non-coding variants within circRNAs, suggesting novel mechanisms for common diseases reported from GWAS studies. For cancer-based somatic variants, we found that chromosome 7 has many highly complex mutations that have been overlooked in previous research.ConclusionWe used the circVAR database to collect SNPs and small insertions and deletions (INDELs) in putative circRNA regions and to identify their potential phenotypic information. To provide a reusable resource for the circRNA research community, we have published all the pre-computed genetic data concerning circRNAs and associated genes together with data query and browsing functions at http://soft.bioinfo-minzhao.org/circvar.

Highlights

  • Circular RNAs play important roles in regulating gene expression through binding miRNAs and RNA binding proteins

  • To help identify putative circRNA-related single nucleotide polymorphism (SNP) and small insertion and deletion (INDEL), we developed the first freely public available database, genetic variant database for human circular RNAs (circVAR), which enables characterization of genetic variants in the human genome

  • These pre-calculated genetic variants of circRNAs provide a comprehensive resource for discovering the commonality or uniqueness of genetic changes for all reported circRNAs

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Summary

Introduction

Circular RNAs (circRNAs) play important roles in regulating gene expression through binding miRNAs and RNA binding proteins. Genetic variation of circRNAs may affect complex traits/diseases by changing their binding efficiency to target miRNAs and proteins. The relationship between variants and expression in circRNA regions has been explored recently, which may provide an uncharacterized role of genetic changes in circRNA expression and regulation [1]. Considering the biological significance of circRNAs, we hypothesize that knowledge of genetic variations in poorly annotated circRNAs may provide insight into their roles in complex traits/diseases. To help identify putative circRNA-related SNPs and INDELs, we developed the first freely public available database, circVAR (http://soft.bioinfo-minzhao.org/ circvar), which enables characterization of genetic variants in the human genome

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