CRAFT: a bioinformatics software for custom prediction of circular RNA functions

Abstract

Circular RNAs (circRNAs), transcripts generated by backsplicing, are particularly stable and pleiotropic molecules, whose dysregulation drives human diseases and cancer by modulating gene expression and signaling pathways. CircRNAs can regulate cellular processes by different mechanisms, including interaction with microRNAs (miRNAs) and RNA-binding proteins (RBP), and encoding specific peptides. The prediction of circRNA functions is instrumental to interpret their impact in diseases, and to prioritize circRNAs for functional investigation. Currently, circRNA functional predictions are provided by web databases that do not allow custom analyses, while self-standing circRNA prediction tools are mostly limited to predict only one type of function, mainly focusing on the miRNA sponge activity of circRNAs. To solve these issues, we developed CRAFT (CircRNA Function prediction Tool), a freely available computational pipeline that predicts circRNA sequence and molecular interactions with miRNAs and RBP, along with their coding potential. Analysis of a set of circRNAs with known functions has been used to appraise CRAFT predictions and to optimize its setting. CRAFT provides a comprehensive graphical visualization of the results, links to several knowledge databases, and extensive functional enrichment analysis. Moreover, it originally combines the predictions for different circRNAs. CRAFT is a useful tool to help the user explore the potential regulatory networks involving the circRNAs of interest and generate hypotheses about the cooperation of circRNAs into the modulation of biological processes.

Circular RNAs Activity in the Leukemic Bone Marrow Microenvironment

“…CircBase is a useful tool in which merged data sets of circRNAs are freely accessible [ 108 ]. Other strong bioinformatics tools are circIMPACT and CRAFT, which are able to identify regulatory networks governed by circRNAs and produce functional predictions [ 109 , 110 ]. From present studies, several circRNAs could be potential diagnostic or prognostic biomarkers for AML.…”

Circular RNA and Its Roles in the Occurrence, Development, Diagnosis of Cancer

“…These artificially established databases are of great significance to the study of the biological functions of circRNAs. In addition to the online database listed in the table, in 2022, the University of Padova developed a circRNA function prediction software CRAFT, which can predict circRNA sequences and molecular interactions with miRNAs and RBPs, as well as their coding potential ( 81 ). Nevertheless, the existing circRNAs collection is largely limited to certain well-studied species, such as humans and mice.…”

Characterization of circular RNAs with advanced sequencing technologies in human complex diseases

“…miRanda (Enright et al, 2003) or RNAhybrid (Kruger & Rehmsmeier, 2006) (Figure 3c). Modern specific computational tools to explore miRNAs-circRNAs are being contiguously developed (Aufiero et al, 2020;Chen et al, 2022;Dal Molin et al, 2022;Dudekula et al, 2016;Table 4), providing alternative ways to search functional miRNA sponging circRNAs.…”