BEAGLE 2.0: A Web Server for RNA Secondary Structure Similarity Detection Leveraging SHAPE-directed RNA Structure Determination

Recent studies underscore the significant role of RNA secondary structures in various biological and pathological processes. Structural conservation can reveal homologies undetectable by sequence analysis alone, making accurate prediction and comparison of RNA secondary structures crucial. The BEAGLE algorithm enables pairwise alignments of RNA secondary structures through dynamic programming, leveraging the BEAR encoding for RNA secondary structures representation. Initially, BEAGLE was designed to perform pairwise alignments of user-provided RNAs or against a limited number of datasets. We now introduce BEAGLE 2.0, a web server designed to facilitate the search for structural similarities between user-provided RNA molecules and an expanded collection of RNA secondary structure datasets. These datasets include structures derived from SHAPE experiments in Homo sapiens, Mus musculus, Danio rerio, Escherichia coli, Bacillus subtilis, and various viruses, including SARS-CoV-2. It also incorporates predicted structures from the NONCODE database for a wide range of animals and plants, as well as a dataset of structures based on constraints derived from conserved positions within the families present in Rfam. Users can input RNA sequences or a combination of sequences and secondary structures in either dot-bracket or BEAR format. BEAGLE 2.0 outputs pairwise alignments with measures of structural similarity and statistical significance. Additionally, it offers a visual representation of the secondary structures, with structural elements highlighted in different colors. Overall, BEAGLE 2.0 enables searches in RNA structure datasets leveraging experimentally supported data, to identify structural similarities in RNAs of interest. BEAGLE 2.0 is available at https://beagle2.bio.uniroma2.it.