Cited by 0Genomics and Phylogenetic StudiesScientific Computing and Data ManagementBioinformatics and Genomic Networks

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nf-core/proteinfamilies: a scalable pipeline for the generation of protein families

Open access
Karatzas, Evangelos, Beracochea, Martin, Baltoumas, Fotis A, Aplakidou, Eleni, Richardson, Lorna, Fellows Yates, James A, Lundin, Daniel, nf-core community, Buluç, Aydin, Kyrpides, Nikos C, Georgakopoulos-Soares, Ilias, Pavlopoulos, Georgios A, Finn, Robert D·2026·GigaScience

Published version of a preprint

Abstract

The growth of metagenomics-derived amino acid sequence data has transformed our understanding of protein function, microbial diversity, and evolutionary relationships. However, the vast majority of these proteins remain functionally uncharacterized. Grouping the millions of such uncharacterized sequences with the few experimentally characterized ones allows the transfer of annotations, while the inspection of conserved residues with multiple sequence alignments can provide clues to function, even in the absence of existing functional information. To address the challenges associated with this data surge and the need to group sequences, we present a scalable, open-source, parametrizable Nextflow pipeline (nf-core/proteinfamilies) that generates nascent protein families or assigns new proteins to existing families. The computational benchmarks demonstrated that resource usage scales approximately linearly with input size, and the biological benchmarks showed that the generated protein families closely resemble manually curated families in widely used databases.

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Research works printed but not linked: 40

  1. Aplakidou, 2024, Visualizing metagenomic and metatranscriptomic data: a comprehensive review, Comput Struct Biotechnol J, 23, 2011, 10.1016/j.csbj.2024.04.060 · DOI
  2. Baltoumas, 2023, Exploring microbial functional biodiversity at the protein family level-from metagenomic sequence reads to annotated protein clusters, Front Bioinform, 3, 1157956, 10.3389/fbinf.2023.1157956 · DOI
  3. UniProt Consortium, 2023, UniProt: the Universal Protein knowledgebase in 2023, Nucleic Acids Res, 51, D523, 10.1093/nar/gkac1052 · DOI · Paper page
  4. Berman, 2000, The Protein Data Bank, Nucleic Acids Res, 28, 235, 10.1093/nar/28.1.235 · DOI · Paper page
  5. O’Leary, 2016, Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation, Nucleic Acids Res, 44, D733, 10.1093/nar/gkv1189 · DOI · Paper page
  6. Sayers, 2022, GenBank, Nucleic Acids Res, 50, D161, 10.1093/nar/gkab1135 · DOI
  7. Chen, 2023, The IMG/M data management and analysis system v.7: content updates and new features, Nucleic Acids Res, 51, D723, 10.1093/nar/gkac976 · DOI
  8. Richardson, 2023, MGnify: the microbiome sequence data analysis resource in 2023, Nucleic Acids Res, 51, D753, 10.1093/nar/gkac1080 · DOI
  9. Mistry, 2021, Pfam: the protein families database in 2021, Nucleic Acids Res, 49, D412, 10.1093/nar/gkaa913 · DOI · Paper page
  10. Paysan-Lafosse, 2023, InterPro in 2022, Nucleic Acids Res, 51, D418, 10.1093/nar/gkac993 · DOI
  11. Baltoumas, 2024, NMPFamsDB: a database of novel protein families from microbial metagenomes and metatranscriptomes, Nucleic Acids Res, 52, D502, 10.1093/nar/gkad800 · DOI
  12. Pavlopoulos, 2023, Unraveling the functional dark matter through global metagenomics, Nature, 622, 594, 10.1038/s41586-023-06583-7 · DOI
  13. Sillitoe, 2012, New functional families (FunFams) in CATH to improve the mapping of conserved functional sites to 3D structures, Nucleic Acids Res, 41, D490, 10.1093/nar/gks1211 · DOI
  14. Huerta-Cepas, 2019, eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses, Nucleic Acids Res, 47, D309, 10.1093/nar/gky1085 · DOI
  15. Cantalapiedra, 2021, eggNOG-mapper v2: functional annotation, orthology assignments, and domain prediction at the metagenomic scale, Mol Biol Evol, 38, 5825, 10.1093/molbev/msab293 · DOI
  16. Kanehisa, 2016, KEGG as a reference resource for gene and protein annotation, Nucleic Acids Res, 44, D457, 10.1093/nar/gkv1070 · DOI · Paper page
  17. Galperin, 2025, COG database update 2024, Nucleic Acids Res, 53, D356, 10.1093/nar/gkae983 · DOI
  18. Tatusov, 2003, The COG database: an updated version includes eukaryotes, BMC Bioinf, 4, 41, 10.1186/1471-2105-4-41 · DOI
  19. Paysan-Lafosse, 2025, The Pfam protein families database: embracing AI/ML, Nucleic Acids Res, 53, D523, 10.1093/nar/gkae997 · DOI
  20. Steinegger, 2017, MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets, Nat Biotechnol, 35, 1026, 10.1038/nbt.3988 · DOI · Paper page
  21. Fu, 2012, CD-HIT: accelerated for clustering the next-generation sequencing data, Bioinformatics, 28, 3150, 10.1093/bioinformatics/bts565 · DOI · Paper page
  22. Di Tommaso, 2017, Nextflow enables reproducible computational workflows, Nat Biotechnol, 35, 316, 10.1038/nbt.3820 · DOI · Paper page
  23. Ewels, 2020, The nf-core framework for community-curated bioinformatics pipelines, Nat Biotechnol, 38, 276, 10.1038/s41587-020-0439-x · DOI
  24. Langer, 2025, Empowering bioinformatics communities with Nextflow and nf-core, 228, 10.1186/s13059-025-03673-9 · DOI
  25. Telatin, 2021, SeqFu: a suite of utilities for the robust and reproducible manipulation of sequence files, Bioengineering, 8, 59, 10.3390/bioengineering8050059 · DOI
  26. Shen, 2024, SeqKit2: a swiss army knife for sequence and alignment processing, iMeta, 3, e191, 10.1002/imt2.191 · DOI
  27. Deorowicz, 2016, FAMSA: fast and accurate multiple sequence alignment of huge protein families, Sci Rep, 6, 33964, 10.1038/srep33964 · DOI
  28. Katoh, 2013, MAFFT multiple sequence alignment software version 7: improvements in performance and usability, Mol Biol Evol, 30, 772, 10.1093/molbev/mst010 · DOI · Paper page
  29. Steenwyk, 2020, ClipKIT: a multiple sequence alignment trimming software for accurate phylogenomic inference, PLoS Biol, 18, e3001007, 10.1371/journal.pbio.3001007 · DOI
  30. Finn, 2011, HMMER web server: interactive sequence similarity searching, Nucleic Acids Res, 39, W29, 10.1093/nar/gkr367 · DOI · Paper page
  31. Ewels, 2016, MultiQC: summarize analysis results for multiple tools and samples in a single report, Bioinformatics, 32, 3047, 10.1093/bioinformatics/btw354 · DOI · Paper page
  32. Santus, 2023, Towards the accurate alignment of over a million protein sequences: current state of the art, Curr Opin Struct Biol, 80, 102577, 10.1016/j.sbi.2023.102577 · DOI
  33. Li, 2021, RefSeq: expanding the Prokaryotic Genome Annotation Pipeline reach with protein family model curation, Nucleic Acids Res, 49, D1020, 10.1093/nar/gkaa1105 · DOI
  34. Thomas, 2003, PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification, Nucleic Acids Res, 31, 334, 10.1093/nar/gkg115 · DOI
  35. Lima, 2009, HAMAP: a database of completely sequenced microbial proteome sets and manually curated microbial protein families in UniProtKB/Swiss-Prot, Nucleic Acids Res, 37, D471, 10.1093/nar/gkn661 · DOI
  36. Buchfink, 2015, Fast and sensitive protein alignment using DIAMOND, Nat Methods, 12, 59, 10.1038/nmeth.3176 · DOI · Paper page
  37. Grüning, 2018, Bioconda: sustainable and comprehensive software distribution for the life sciences, Nat Methods, 15, 475, 10.1038/s41592-018-0046-7 · DOI
  38. Merkel, 2014, Docker: lightweight Linux containers for consistent development and deployment, Linux J, 2, 22014, 10.5555/2600239.2600241 · DOI
  39. Kurtzer, 2017, Singularity: scientific containers for mobility of compute, PLoS One, 12, e0177459, 10.1371/journal.pone.0177459 · DOI · Paper page
  40. Van Kempen, 2024, Fast and accurate protein structure search with Foldseek, Nat Biotechnol, 42, 243, 10.1038/s41587-023-01773-0 · DOI · Paper page

Metadata

Authors
Karatzas, E., Beracochea, M., Baltoumas, F. A., Aplakidou, E., Richardson, L., Fellows Yates, J. A., Lundin, D., community, N.-C., Buluç, A., Kyrpides, N. C., Georgakopoulos-Soares, I., Pavlopoulos, G. A., & Finn, R. D.
Affiliations
  • European Bioinformatics Institute (GB)
  • European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI) , Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD ,
  • Alexander Fleming Biomedical Sciences Research Center (GR)
  • University of Crete (GR)
  • Max Planck Institute for Evolutionary Anthropology Department of Archaeogenetics, , Deutscher Pl. 6, Leipzig 04103 ,
  • Stockholm University (SE)
  • Applied Mathematics and Computational Research Division (AMCR), Lawrence Berkeley National Laboratory , 1 Cyclotron Road, Berkeley, CA 94720 ,
  • Lawrence Berkeley National Laboratory (US)
  • College of Pharmacy, The University of Texas at Austin, Dell Paediatric Research Institute Division of Pharmacology and Toxicology, , 1400 Barbara Jordan Blvd., Austin, TX 78723 ,
  • Mohamed bin Zayed University of Artificial Intelligence (AE)
Corresponding author
Finn, Robert D
Venue
GigaScience
Published
2026
Volume
15
ISSN
2047-217X (ISSN-L)
OpenAlex
W7125234690
Cited by
0
References
1
FWCI
0.00
Type
journal article
Language
en
Open access
Locations
  • GigaScience (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
  • DiVA (Linnaeus University) (submittedVersion, other-oa)
Funders
  • European Union
  • Hellenic Foundation for Research and Innovation (DE-AC02-05CH11231)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Social Sciences › Decision Sciences › Information Systems and Management › Scientific Computing and Data Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
protein families, metagenomics, hypothetical protein, protein annotation, multiple sequence alignment, conserved residues, Nextflow pipeline, protein family clustering
MeSH terms
Algorithms, Amino Acid Sequence, Proteins, Software, Sequence Alignment, Computational Biology, Databases, Protein, Metagenomics, Molecular Sequence Annotation

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