Microbial abundance, activity and population genomic profiling with mOTUs2
Open accessAbstract
Metagenomic sequencing has greatly improved our ability to profile the composition of environmental and host-associated microbial communities. However, the dependency of most methods on reference genomes, which are currently unavailable for a substantial fraction of microbial species, introduces estimation biases. We present an updated and functionally extended tool based on universal (i.e., reference-independent), phylogenetic marker gene (MG)-based operational taxonomic units (mOTUs) enabling the profiling of >7700 microbial species. As more than 30% of them could not previously be quantified at this taxonomic resolution, relative abundance estimates based on mOTUs are more accurate compared to other methods. As a new feature, we show that mOTUs, which are based on essential housekeeping genes, are demonstrably well-suited for quantification of basal transcriptional activity of community members. Furthermore, single nucleotide variation profiles estimated using mOTUs reflect those from whole genomes, which allows for comparing microbial strain populations (e.g., across different human body sites).
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MetaPhlAn 2.7, mOTUs 2.51, and Bracken 2.5 have consistently been shown to outperform other methods across multiple evaluations.
“These three profiling tools have consistently been shown to outperform other methods across multiple evaluations (McIntyre et al., 2017; Meyer et al., 2019; Milanese et al., 2019; Sczyrba et al., 2017; Truong et al., 2015; Ye et al., 2019).”
From Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3 (2021) · cites this paper as Milanese et al., 2019
Additional phylogenetic marker gene-based operational taxonomic unit profiling is performed using mOTUs2 on all reads that pass QC, which allows sensitive and accurate quantification for both known and unknown species.
“Additional phylogenetic marker gene-based operational taxonomic unit profiling is performed using mOTUs2 (35) on all reads that pass QC, which allows sensitive and accurate quantification for both known and unknown species.”
From MGnify: the microbiome analysis resource in 2020 (2019) · cites this paper as [35]
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- Authors
- Milanese, A., Mende, D. R., Paoli, L., Salazar, G., Ruscheweyh, H.-J., Cuenca, M., Hingamp, P., Alves, R., Costea, P. I., Coelho, L. P., Schmidt, T. S. B., Almeida, A., Mitchell, A. L., Finn, R. D., Huerta-Cepas, J., Bork, P., Zeller, G., & Sunagawa, S.
- Affiliations
- European Molecular Biology Laboratory (DE)
- University of Hawaiʻi at Mānoa (US)
- SIB Swiss Institute of Bioinformatics (CH)
- Centre National de la Recherche Scientifique (FR)
- Heidelberg University (DE)
- European Bioinformatics Institute (GB)
- Corresponding author
- Zeller, Georg
- Sunagawa, Shinichi
- ORCID
- Venue
- Nature Communications
- Published
- 2019-03-04
- Volume
- 10
- Issue
- 1
- Pages
- 1014-1014
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6399450
- OpenAlex
- W2920716817
- Cited by
- 446
- References
- 59
- Citations by year
- 2026: 24 · 2025: 43 · 2024: 74 · 2023: 73 · 2022: 89 · 2021: 82 · 2020: 42 · 2019: 17
- FWCI
- 20.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- HAL (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- ETH Zürich Research Collection (cc-by)
- Funders
- European Molecular Biology Organization (GA-2013-609409, ALTF 721-2015, LTFCOFUND2013)
- Novartis Foundation (LTFCOFUND2013, GA-2013-609409)
- Bundesministerium für Bildung und Forschung (031A537B)
- Eidgenössische Technische Hochschule Zürich (PHRT 521)
- Novartis Stiftung für Medizinisch-Biologische Forschung
- Helmut Horten Stiftung
- German Network for Bioinformatics Infrastructure (031 A537B)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- operational taxonomic units, housekeeping genes, microbial community composition, single nucleotide variants, human microbiome, metagenomics
- MeSH terms
- Host Microbial Interactions, Algorithms, Genetic Markers, Humans, Phylogeny, Cluster Analysis, Sequence Alignment, Genome, Sequence Analysis, DNA, Computational Biology, Genes, Essential, Gene Expression Profiling, Metagenomics, Molecular Sequence Annotation, Microbiota
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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