Multiple levels of the unknown in microbiome research
Open accessAbstract
Metagenomics allows exploration of aspects of a microbial community that were inaccessible by cultivation-based approaches targeting single microbes. Many new microbial taxa and genes have been discovered using metagenomics, but different kinds of "unknowns" still remain in a microbiome experiment. We discuss here whether and how it is possible to deal with them.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
20%-50% of shotgun metagenomic reads cannot be mapped.
“Based on what is known and what is feasible, 20%-50% of shotgun metagenomic reads cannot be mapped, 30%-50% of identified genes are of unknown function, and most strikingly, 80%-90% of metabolites cannot be identified. 135,147”
From Key determinants of success in fecal microbiota transplantation: From microbiome to clinic (2023) · cites this paper as [147]
Complete characterization of stool composition is so far impossible to achieve, even with the most recent multiomic approaches.
“However, the complete characterization of stool composition is so far impossible to achieve, even with the most recent multiomic approaches.”
From Key determinants of success in fecal microbiota transplantation: From microbiome to clinic (2023) · cites this paper as [147]
80%-90% of metabolites cannot be identified.
“Based on what is known and what is feasible, 20%-50% of shotgun metagenomic reads cannot be mapped, 30%-50% of identified genes are of unknown function, and most strikingly, 80%-90% of metabolites cannot be identified. 135,147”
From Key determinants of success in fecal microbiota transplantation: From microbiome to clinic (2023) · cites this paper as [147]
30%-50% of identified genes are of unknown function.
“Based on what is known and what is feasible, 20%-50% of shotgun metagenomic reads cannot be mapped, 30%-50% of identified genes are of unknown function, and most strikingly, 80%-90% of metabolites cannot be identified. 135,147”
From Key determinants of success in fecal microbiota transplantation: From microbiome to clinic (2023) · cites this paper as [147]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Insights into the phylogeny and coding potential of microbial dark matter
Rinke, C., Schwientek, P., Sczyrba, A., Ivanova, N. N., Anderson, I. J., Cheng, J.-F., Darling, A., Malfatti, S., Swan, B. K., Gies, E. A., et al. (2013) · Nature · doi:10.1038/nature12352 · Cited by 2,394 · see citing works
Shotgun metagenomics, from sampling to analysis
Quince, C., Walker, A. W., Simpson, J. T., Loman, N. J., & Segata, N. (2017) · Nature Biotechnology · doi:10.1038/nbt.3935 · Cited by 2,202 · see citing works
Self-citationAn integrated catalog of reference genes in the human gut microbiome
MetaHIT Consortium, Li, J., Jia, H., Cai, X., Zhong, H., Feng, Q., Sunagawa, S., Arumugam, M., Kultima, J. R., Prifti, E., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.2942 · Cited by 2,164 · see citing works
Recovery of nearly 8,000 metagenome-assembled genomes substantially expands the tree of life
Parks, D. H., Rinke, C., Chuvochina, M., Chaumeil, P.-A., Woodcroft, B. J., Evans, P. N., Hugenholtz, P., & Tyson, G. W. (2017) · Nature Microbiology · doi:10.1038/s41564-017-0012-7 · Cited by 1,882 · see citing works
Pasolli, E., Asnicar, F., Manara, S., Zolfo, M., Karcher, N., Armanini, F., Beghini, F., Manghi, P., Tett, A., Ghensi, P., et al. (2019) · Cell · doi:10.1016/j.cell.2019.01.001 · Cited by 1,591 · see citing works
Self-citationA new genomic blueprint of the human gut microbiota
Almeida, A., Mitchell, A. L., Boland, M., Forster, S. C., Gloor, G. B., Tarkowska, A., Lawley, T. D., & Finn, R. D. (2019) · Nature · doi:10.1038/s41586-019-0965-1 · Cited by 1,314 · see citing works
Unusual biology across a group comprising more than 15% of domain Bacteria
Brown, C. T., Hug, L. A., Thomas, B. C., Sharon, I., Castelle, C. J., Singh, A., Wilkins, M. J., Wrighton, K. C., Williams, K. H., & Banfield, J. F. (2015) · Nature · doi:10.1038/nature14486 · Cited by 1,216 · see citing works
Microbial culturomics: paradigm shift in the human gut microbiome study
Lagier, J., Armougom, F., Million, M., Hugon, P., Pagnier, I., Robert, C., Bittar, F., Fournous, G., Gimenez, G., Maraninchi, M., et al. (2012) · Clinical Microbiology and Infection · doi:10.1111/1469-0691.12023 · Cited by 1,200 · see citing works
Thomas, A. M., Manghi, P., Asnicar, F., Pasolli, E., Armanini, F., Zolfo, M., Beghini, F., Manara, S., Karcher, N., Pozzi, C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0405-7 · Cited by 1,030 · see citing works
Self-citationNew insights from uncultivated genomes of the global human gut microbiome
Nayfach, S., Shi, Z. J., Seshadri, R., Pollard, K. S., & Kyrpides, N. C. (2019) · Nature · doi:10.1038/s41586-019-1058-x · Cited by 737 · see citing works
Marcy, Y., Ouverney, C., Bik, E. M., Lösekann, T., Ivanova, N., Martín, H. G., Szeto, E., Platt, D., Hugenholtz, P., Relman, D. A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704662104 · Cited by 632 · see citing works
1,520 reference genomes from cultivated human gut bacteria enable functional microbiome analyses
Zou, Y., Xue, W., Luo, G., Deng, Z., Qin, P., Guo, R., Sun, H., Xia, Y., Liang, S., Dai, Y., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-018-0008-8 · Cited by 526 · see citing works
Exploring microbial dark matter to resolve the deep archaeal ancestry of eukaryotes
Saw, J. H. W., Spang, A., Zaremba-Niedźwiedzka, K., Juzokaite, L., Dodsworth, J. A., Murugapiran, S. K., Colman, D. R., Takacs‐Vesbach, C. D., Hedlund, B. P., Guy, L., et al. (2015) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2014.0328 · Cited by 80 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Beghini, F., McIver, L. J., Blanco-Míguez, A., Dubois, L., Asnicar, F., Maharjan, S., Mailyan, A., Manghi, P., Scholz, M., Thomas, A. M., et al. (2021) · eLife · doi:10.7554/elife.65088 · Cited by 2,303 · see citing works
Self-citationBlanco-Míguez, A., Beghini, F., Cumbo, F., McIver, L. J., Thompson, K. N., Zolfo, M., Manghi, P., Dubois, L., Huang, K. D., Thomas, A. M., et al. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01688-w · Cited by 1,442 · see citing works
Self-citationA unified catalog of 204,938 reference genomes from the human gut microbiome
Almeida, A., Nayfach, S., Boland, M., Strozzi, F., Beracochea, M., Shi, Z. J., Pollard, K. S., Sakharova, E., Parks, D. H., Hugenholtz, P., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-020-0603-3 · Cited by 1,367 · see citing works
Self-citationAsnicar, F., Thomas, A. M., Beghini, F., Mengoni, C., Manara, S., Manghi, P., Zhu, Q., Bolzan, M., Cumbo, F., May, U., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16366-7 · Cited by 869 · see citing works
Self-citationDiet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health
Berding, K., Vlckova, K., Marx, W., Schellekens, H., Stanton, C., Clarke, G., Jacka, F., Dinan, T. G., & Cryan, J. F. (2021) · Advances in Nutrition · doi:10.1093/advances/nmaa181 · Cited by 451 · see citing works
Large-scale genome-wide analysis links lactic acid bacteria from food with the gut microbiome
Pasolli, E., De Filippis, F., Mauriello, I. E., Cumbo, F., Walsh, A. M., Leech, J., Cotter, P. D., Segata, N., & Ercolini, D. (2020) · Nature Communications · doi:10.1038/s41467-020-16438-8 · Cited by 367 · see citing works
Self-citationBeresford-Jones, B. S., Forster, S. C., Stares, M. D., Notley, G., Viciani, E., Browne, H. P., Boehmler, D. J., Soderholm, A. T., Kumar, N., Vervier, K., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2021.12.003 · Cited by 194 · see citing works
Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy
Thomas, A. M., Fidelle, M., Routy, B., Kroemer, G., Wargo, J. A., Segata, N., & Zitvogel, L. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00785-8 · Cited by 141 · see citing works
Self-citationGastrointestinal involvement of autism spectrum disorder: focus on gut microbiota
Settanni, C. R., Bibbò, S., Ianiro, G., Rinninella, E., Cintoni, M., Mele, M. C., Cammarota, G., & Gasbarrini, A. (2021) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2021.1869938 · Cited by 98 · see citing works
Dargenio, V. N., Dargenio, C., Castellaneta, S., De Giacomo, A., Laguardia, M., Schettini, F., Francavilla, R., & Cristofori, F. (2023) · Nutrients · doi:10.3390/nu15071620 · Cited by 98 · see citing works
Targeting the human gut microbiome with small-molecule inhibitors
Woo, A. Y. M., Aguilar Ramos, M. A., Narayan, R., Richards-Corke, K. C., Wang, M. L., Sandoval-Espinola, W. J., & Balskus, E. P. (2023) · Nature Reviews Chemistry · doi:10.1038/s41570-023-00471-4 · Cited by 42 · see citing works
- Authors
- Thomas, A. M., & Segata, N.
- Affiliations
- University of Trento (IT)
- Corresponding author
- Segata, Nicola
- Venue
- BMC Biology
- Published
- 2019-06-12
- Volume
- 17
- Issue
- 1
- Pages
- 48-48
- ISSN
- 1741-7007 (ISSN-L)
- PMC
- PMC6560723
- OpenAlex
- W2950447040
- Cited by
- 176
- References
- 13
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 25 · 2023: 23 · 2022: 29 · 2021: 36 · 2020: 25 · 2019: 4
- FWCI
- 8.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion, cc-by)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca (H2020, RBFR13EWWI_001)
- LEO Pharma
- Horizon 2020 Framework Programme (MASTER-818368, OncoBiome 825410, 818368, ONCOBIOME-825410 project, MASTER-818368 project, 825410)
- H2020 European Research Council (716575)
- 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
- microbiome research, metagenomics, microbial communities, unculturable microorganisms, unknown genes, microbial diversity, experimental design
- MeSH terms
- Archaea, Bacteria, Bacterial Physiological Phenomena, Metagenome, Metagenomics, 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 ›
Are you an author, or do you see a problem with this page? Request a review