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Updated: Jun 27, 2025

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
Published on: December 9, 2022
SHAPEwarp-web: sequence-agnostic search for structurally homologous RNA regions across databases of chemical probing
Niek R Scholten1, Dennis Haandrikman1, Joshua O Tolhuis1
1School for Life Science and Technology, Hanze University of Applied Sciences, 9747 AS Groningen, The Netherlands.
Abstract:
RNA molecules perform a variety of functions in cells, many of which rely on their secondary and tertiary structures. Chemical probing methods coupled with high-throughput sequencing have significantly accelerated the mapping of RNA structures, and increasingly large datasets of transcriptome-wide RNA chemical probing data are becoming available. Analogously to what has been done for decades in the protein world, this RNA structural information can be leveraged to aid the discovery of structural similarity to a known RNA (or RNA family), which, in turn, can inform about the function of transcripts. We have previously developed SHAPEwarp, a sequence-agnostic method for the search of structurally homologous RNA segments in a database of reactivity profiles derived from chemical probing experiments. In its original implementation, however, SHAPEwarp required substantial computational resources, even for moderately sized databases, as well as significant Linux command line know-how. To address these limitations, we introduce here SHAPEwarp-web, a user-friendly web interface to rapidly query large databases of RNA chemical probing data for structurally similar RNAs. Aside from featuring a completely rewritten core, which speeds up by orders of magnitude the search inside large databases, the web server hosts several high-quality chemical probing databases across multiple species. SHAPEwarp-web is available from https://shapewarp.incarnatolab.com.
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