Cited by 4,840Genomics and Phylogenetic StudiesAlgorithms and Data CompressionAdvanced Proteomics Techniques and Applications

MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets

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Steinegger, Martin, Söding, Johannes·2017·Nature Biotechnology

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Crossref · 10.1038/nbt.3988

Cites

24 of 24 references verified0 citation errors · 0 not checkable

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  • The dataset was clustered using MMseqs2 at minimum 30% sequence identity to avoid bias towards a certain class in the test set.

    “All individual chains in each category were then clustered using MMseqs2(16) using a minimum sequence identity of 30%, and the centerpoints of each cluster were selected.This was to avoid bias towards a certain class in the test set.”

    From Reliable Identification of Homodimers Using AlphaFold (2025) · cites this paper as [16]

  • ColabFold's homology search is 40-60-fold faster than AlphaFold2's.

    “ColabFold’s 40−60-fold faster search and optimized model utilization enables prediction of close to 1,000 structures per day on a server with one graphics processing unit.”

    From ColabFold - Making protein folding accessible to all (2021) · cites this paper as [10]

  • The first clustering step used MMseqs2 to cluster 214,684,311 structures into 52,327,413 sequence clusters at 50% sequence identity and 90% sequence alignment overlap.

    “The first step involved using MMseqs2 (ref. 23) to cluster the database on the basis of 50% sequence identity and a 90% sequence alignment overlap of both sequences, resulting in 52,327,413 clusters.”
  • Sequence searching is four to five orders of magnitude faster: an all-versus-all comparison of 100 million sequences would take MMseqs2 only around a week on the same cluster.

    “Sequence searching is four to five orders of magnitude faster: an all-versus-all comparison of 100 million sequences would take MMseqs2 (ref. 6) only around a week on the same cluster.”

    From Fast and accurate protein structure search with Foldseek (2024) · cites this paper as [6]

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Research works printed but not linked: 14

  1. [3]3. M. Farrar. Striped Smith-Waterman speeds database searches six times over other SIMD implementations. Bioinformatics, 23(2):156-161, Jan. 2007.
  2. [6]6. M. W. Gonzalez and W. R. Pearson. Homologous over-extension: a challenge for iterative similarity searches. Nucleic Acids Res., 38(7):2177-2189, 2010.
  3. [7]7. M. Hauser, C. E. Mayer, and J. Söding. kclust: fast and sensitive clustering of large protein sequence databases. BMC Bioinformatics, 14(1):1-12, 2013.
  4. [9]9. H. Hauswedell, J. Singer, and K. Reinert. Lambda: the local aligner for massive biological data. Bioinformatics, 30(17):i349-i355, 2014.
  5. [10]10. D. H. Huson and C. Xie. A poor man's BLASTX-high-throughput metagenomic protein database search using PAUDA. Bioinformatics, 30(1):38-39, 2014.
  6. [12]12. J. J. Kent. BLAT-the BLAST-like alignment tool. Genome Res., 12(4):656-664, Apr. 2002.
  7. [13]13. B. Ma, J. Tromp, and M. Li. PatternHunter: faster and more sensitive homology search. Bioinformatics, 18(3):440-445, 2002.
  8. [15]15. M. Remmert, A. Biegert, A. Hauser, and J. Söding. HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nature Methods, 9(2):173-175, Feb. 2012.
  9. [17]17. S. A. Shiryev, J. S. Papadopoulos, A. A. Schäffer, and R. Agarwala. Improved blast searches using longer words for protein seeding. Bioinformatics, 23(21):2949-2951, 2007.
  10. [18]18. J. Söding. Protein homology detection by HMM-HMM comparison. Bioinformatics, 21(7):951-960, 2005.
  11. [19]19. J. Söding and M. Remmert. Protein sequence comparison and fold recognition: progress and good-practice benchmarking. Curr. Opin. Struct. Biol., 21(3):404-411, 2011.
  12. [20]20. J. Tan, D. Kuchibhatla, F. L. Sirota, W. A. Sherman, T. Gattermayer, C. Y. Kwoh, F. Eisenhaber, G. Schneider, and S. M. Stroh. Tachyon search speeds up retrieval of similar sequences by several orders of magnitude. Bioinformatics, 28(12):1645-1646, June 2012.
  13. [21]21. R. Vaser, D. Pavlović, M. Korpar, and M. Šikić. Sword-a highly efficient protein database search. Bioinformatics, 32(17):i680-i684, 2016.
  14. [22]22. M. Zhao, W.-P. Lee, E. P. Garrison, and G. T. Marth. Ssw library: An simd smith-waterman c/c++ library for use in genomic applications. PLoS One, 8(12), 12 2013.

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Authors
Steinegger, M., & Söding, J.
Affiliations
Max Planck Institute for Biophysical Chemistry (DE)
Corresponding author
Söding, Johannes
Venue
Nature Biotechnology
Published
2017-10-16
Volume
35
Issue
11
Pages
1026-1028
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W2950954328
Cited by
4,840
References
24
Citations by year
2026: 1165 · 2025: 1239 · 2024: 966 · 2023: 591 · 2022: 400 · 2021: 238 · 2020: 141 · 2019: 64 · 2018: 26 · 2017: 8 · 2012: 2
FWCI
26.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Biotechnology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • Seoul National University Open Repository (Seoul National University) (submittedVersion)
Funders
  • Bundesministerium für Bildung und Forschung
  • Seoul National University
  • Horizon 2020 Framework Programme
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Physical Sciences › Computer Science › Artificial Intelligence › Algorithms and Data Compression
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
MMseqs2, sequence clustering, big data, bioinformatics software
MeSH terms
Algorithms, Database Management Systems, Software, Sequence Alignment, Sequence Analysis, Protein, Databases, Protein

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