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Cirscan: a shiny application to identify differentially active sponge mechanisms and visualize circRNA-miRNA-mRNA
Rose-Marie Fraboulet1, Yanis Si Ahmed1, Marc Aubry2
1Univ Rennes, CNRS, INSERM, IGDR (Institut de Genetique et Developpement de Rennes) - UMR 6290, ERL U1305, Equipe Labellisée Ligue Nationale contre le Cancer, 35000, Rennes, France.
Background:
Non-coding RNAs represent a large part of the human transcriptome and have been shown to play an important role in disease such as cancer. However, their biological functions are still incompletely understood. Among non-coding RNAs, circular RNAs (circRNAs) have recently been identified for their microRNA (miRNA) sponge function which allows them to modulate the expression of miRNA target genes by taking on the role of competitive endogenous RNAs (ce-circRNAs). Today, most computational tools are not adapted to the search for ce-circRNAs or have not been developed for the search for ce-circRNAs from user's transcriptomic data.
Results:
In this study, we present Cirscan (CIRcular RNA Sponge CANdidates), an interactive Shiny application that automatically infers circRNA-miRNA-mRNA networks from human multi-level transcript expression data from two biological conditions (e.g. tumor versus normal conditions in the case of cancer study) in order to identify on a large scale, potential sponge mechanisms active in a specific condition. Cirscan ranks each circRNA-miRNA-mRNA subnetwork according to a sponge score that integrates multiple criteria based on interaction reliability and expression level. Finally, the top ranked sponge mechanisms can be visualized as networks and an enrichment analysis is performed to help its biological interpretation. We showed on two real case studies that Cirscan is capable of retrieving sponge mechanisms previously described, as well as identifying potential novel circRNA sponge candidates.
Conclusions:
Cirscan can be considered as a companion tool for biologists, facilitating their ability to prioritize sponge mechanisms for experimental validations and identifying potential therapeutic targets. Cirscan is implemented in R, released under the license GPL-3 and accessible on GitLab ( https://gitlab.com/geobioinfo/cirscan_Rshiny ). The scripts used in this paper are also provided on Gitlab ( https://gitlab.com/geobioinfo/cirscan_paper ).
Insights
This study introduces Cirscan, a tool to identify circular RNA (circRNA) and microRNA (miRNA) interactions in gene expression data. Cirscan helps researchers find potential therapeutic targets by analyzing competitive endogenous RNA (ceRNA) networks.
Area of Science:
- Genomics
- Bioinformatics
- Molecular Biology
Background:
- Non-coding RNAs, including circular RNAs (circRNAs), are crucial in disease pathogenesis like cancer, but their functions are not fully understood.
- circRNAs act as microRNA (miRNA) sponges, functioning as competitive endogenous RNAs (ceRNAs) to regulate miRNA target gene expression.
- Existing computational tools are limited for identifying ce-circRNAs from user-specific transcriptomic data.
Purpose of the Study:
- To develop an interactive application, Cirscan, for inferring circRNA-miRNA-mRNA networks.
- To identify potential circRNA sponge mechanisms within specific biological conditions using transcriptomic data.
- To provide a scalable solution for discovering ce-circRNA interactions.
Main Methods:
- Cirscan is an interactive Shiny application that analyzes multi-level human transcript expression data from two conditions.
- It automatically infers circRNA-miRNA-mRNA networks and ranks subnetworks using a 'sponge score'.
- The score integrates interaction reliability and expression levels to prioritize potential sponge mechanisms.
Main Results:
- Cirscan successfully identifies known and novel circRNA sponge mechanisms in real case studies.
- The application visualizes top-ranked sponge mechanisms as networks and performs enrichment analysis for biological interpretation.
- It enables large-scale identification of condition-specific circRNA sponge activities.
Conclusions:
- Cirscan serves as a valuable tool for biologists to prioritize circRNA sponge mechanisms for experimental validation.
- It aids in identifying potential therapeutic targets by revealing key regulatory interactions.
- The R-based application is accessible on GitLab, promoting collaborative research and development.
