Annotating the microbial dark matter with HiFi-NN

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  • dc.contributor.author Ayres, Gavin
  • dc.contributor.author Munsamy, Geraldene
  • dc.contributor.author Heinzinger, Michael
  • dc.contributor.author Ferruz Capapey, Noelia, 1988-
  • dc.contributor.author Yang, Kevin
  • dc.contributor.author Bergman, Bastiaan
  • dc.contributor.author Lorenz, Philipp
  • dc.date.accessioned 2025-09-05T06:25:04Z
  • dc.date.available 2025-09-05T06:25:04Z
  • dc.date.issued 2025
  • dc.description.abstract The accurate computational annotation of protein sequences with enzymatic function remains a fundamental challenge in bioinformatics. Here, we present HiFi-NN (Hierarchically-Finetuned Nearest Neighbor search) which annotates protein sequences to the 4th level of Enzyme Commission (EC) number with greater precision and recall than state-of-the-art deep learning methods. Furthermore, we show that this method can correctly identify the EC number of a given sequence to lower identities than BLASTp. We show that performance can be improved by increasing the diversity of the lookup set in both sequence space and the environment the sequence has been sampled from. We proceed to show that we can correct specific mis-annotations in the BRENDA enzymes database reproducing results found by others. Finally, we use HiFi-NN to annotate functional dark-matter protein sequences from NMPFamDB. Our findings pave the way for more accurate functional annotation in silico, especially for proteins from distant sequence space.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Ayres G, Munsamy G, Heinzinger M, Ferruz N, Yang K, Bergman B, et al. Annotating the microbial dark matter with HiFi-NN. iScience. 2025 Apr 18;28(6):112480. DOI: 10.1016/j.isci.2025.112480
  • dc.identifier.doi http://dx.doi.org/10.1016/j.isci.2025.112480
  • dc.identifier.issn 2589-0042
  • dc.identifier.uri http://hdl.handle.net/10230/71117
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof iScience. 2025 Apr 18;28(6):112480
  • dc.rights © 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Computer science
  • dc.subject.keyword Microbiology
  • dc.title Annotating the microbial dark matter with HiFi-NN
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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Articles (Center for Genomic Regulation (CRG))