环状RNA海绵作用:一种用于广泛分析环状RNA表达及其在微小RNA海绵作用中作用的流程。

circRNA-sponging: a pipeline for extensive analysis of circRNA expression and their role in miRNA sponging.

作者信息

Hoffmann Markus, Schwartz Leon, Ciora Octavia-Andreea, Trummer Nico, Willruth Lina-Liv, Jankowski Jakub, Lee Hye Kyung, Baumbach Jan, Furth Priscilla A, Hennighausen Lothar, List Markus

机构信息

Big Data in BioMedicine Group, Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Freising D-85354, Germany.

Institute for Advanced Study, Technical University of Munich, Garching D-85748, Germany.

出版信息

Bioinform Adv. 2023 Jul 8;3(1):vbad093. doi: 10.1093/bioadv/vbad093. eCollection 2023.

Abstract

MOTIVATION

Circular RNAs (circRNAs) are long noncoding RNAs (lncRNAs) often associated with diseases and considered potential biomarkers for diagnosis and treatment. Among other functions, circRNAs have been shown to act as microRNA (miRNA) sponges, preventing the role of miRNAs that repress their targets. However, there is no pipeline to systematically assess the sponging potential of circRNAs.

RESULTS

We developed circRNA-sponging, a nextflow pipeline that (i) identifies circRNAs via backsplicing junctions detected in RNA-seq data, (ii) quantifies their expression values in relation to their linear counterparts spliced from the same gene, (iii) performs differential expression analysis, (iv) identifies and quantifies miRNA expression from miRNA-sequencing (miRNA-seq) data, (v) predicts miRNA binding sites on circRNAs, (vi) systematically investigates potential circRNA-miRNA sponging events, (vii) creates a network of competing endogenous RNAs and (viii) identifies potential circRNA biomarkers. We showed the functionality of the circRNA-sponging pipeline using RNA sequencing data from brain tissues, where we identified two distinct types of circRNAs characterized by a specific ratio of the number of the binding site to the length of the transcript. The circRNA-sponging pipeline is the first end-to-end pipeline to identify circRNAs and their sponging systematically with raw total RNA-seq and miRNA-seq files, allowing us to better indicate the functional impact of circRNAs as a routine aspect in transcriptomic research.

AVAILABILITY AND IMPLEMENTATION

https://github.com/biomedbigdata/circRNA-sponging.

SUPPLEMENTARY INFORMATION

Supplementary data are available at online.

摘要

动机

环状RNA(circRNA)是一类长链非编码RNA(lncRNA),常与疾病相关,被认为是诊断和治疗的潜在生物标志物。除其他功能外,circRNA已被证明可作为微小RNA(miRNA)的海绵,阻止miRNA对其靶标的抑制作用。然而,目前尚无系统评估circRNA海绵化潜力的流程。

结果

我们开发了circRNA-sponging,这是一个Nextflow流程,它(i)通过RNA测序数据中检测到的反向剪接接头来识别circRNA,(ii)相对于从同一基因剪接而来的线性对应物量化其表达值,(iii)进行差异表达分析,(iv)从miRNA测序(miRNA-seq)数据中识别和量化miRNA表达,(v)预测circRNA上的miRNA结合位点,(vi)系统地研究潜在的circRNA-miRNA海绵化事件,(vii)创建竞争性内源RNA网络,以及(viii)识别潜在的circRNA生物标志物。我们使用脑组织的RNA测序数据展示了circRNA-sponging流程的功能,在该数据中我们识别出两种不同类型的circRNA,其特征在于结合位点数量与转录本长度的特定比例。circRNA-sponging流程是首个利用原始总RNA-seq和miRNA-seq文件系统识别circRNA及其海绵化作用的端到端流程,使我们能够在转录组学研究中更好地将circRNA的功能影响作为常规方面进行指示。

可用性和实现方式

https://github.com/biomedbigdata/circRNA-sponging。

补充信息

补充数据可在在线获取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b78/10359604/3f3c8560c196/vbad093f1.jpg

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