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EasyCircR:转录后调控相互作用网络中环状RNA的检测与重构

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

作者信息

Aparo Antonino, Avesani Simone, Parmigiani Luca, Napoli Sara, Bertoni Francesco, Bonnici Vincenzo, Cascione Luciano, Giugno Rosalba

机构信息

Department of Computer Science, University of Verona, Strada le Grazie, 15, Verona, 37134, Italy; Research Center LURM (Interdepartmental Laboratory of Medical Research), University of Verona, Verona, 37134, Italy.

Department of Computer Science, University of Verona, Strada le Grazie, 15, Verona, 37134, Italy.

出版信息

Comput Biol Med. 2025 Apr;188:109846. doi: 10.1016/j.compbiomed.2025.109846. Epub 2025 Feb 22.

Abstract

Circular RNAs (circRNAs) are regulatory RNAs that play a crucial role in various biological activities and have been identified as potential biomarkers for 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 modifications. Additionally, some circRNAs operate as microRNA (miRNA) sponges in the cytoplasm, boosting post-transcriptional expression of target genes by inhibiting miRNA activity. Although existing pipelines can 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, avoiding considering potential target mRNAs not regulated at the post-transcriptional level. 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, leveraging the post-transcriptional regulatory nature of circRNA-miRNA relationship and excluding unrealistic regulatory interactions at the biological level. EasyCircR source code, Docker container and user guide are available at: https://github.com/InfOmics/EasyCircR.

摘要

环状RNA(circRNAs)是一类调控性RNA,在各种生物活动中发挥着关键作用,并且已被确定为神经疾病和癌症的潜在生物标志物。circRNAs通过不同机制成为基因表达的重要调节因子,包括转录和剪接调控、翻译调节以及翻译后修饰。此外,一些circRNAs在细胞质中充当微小RNA(miRNA)海绵,通过抑制miRNA活性来促进靶基因的转录后表达。尽管现有流程可以重建circRNAs、识别被其吸附的miRNAs、检索级联调控的mRNAs,并将调控相互作用表示为复杂的circRNA-miRNA-mRNA网络,但目前最先进的方法都无法区分相互作用中涉及的mRNAs在哪个生物学水平受到调控,从而避免考虑那些在转录后水平不受调控的潜在靶mRNAs。EasyCircR是一个新颖的R包,它将circRNA检测和重建与转录后基因表达分析(外显子-内含子拆分分析)以及miRNA反应元件预测相结合。该软件包通过一个直观的Shiny应用程序,利用circRNA-miRNA关系的转录后调控性质,并排除生物学水平上不现实的调控相互作用,实现对circRNA-miRNA-mRNA相互作用的估计和可视化。EasyCircR的源代码、Docker容器和用户指南可在以下网址获取:https://github.com/InfOmics/EasyCircR。

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