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Fast remote nucleotide sequence alignment with Riboseek

Preprint Created on 01 Aug 2026 bioRxiv

Structure prediction has reached RNA, where generating deep alignments is now the bottleneck. We developed Riboseek, a search and alignment tool for RNA and DNA that represents sequences as overlapping di-mers. Riboseek is more sensitive for homology detection than BLASTN and nhmmer, and generates alignments 250- and 376-fold faster than nhmmer and rMSA. With structure-aware realignment, it approaches rMSA's base-pair recovery, while remaining 29-fold faster. We provide a web server and 1.7 million precomputed alignments for putatively structured RNAs. Riboseek is freely available at https://github.com/steineggerlab/riboseek.

Park, S., Didi, K., Favor, A., Bushuiev, A., Kim, S., Mirdita, M., Steinegger, M.

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