Novel Fecal Biomarkers That Precede Clinical Diagnosis of Ulcerative Colitis
Abstract
Background & aims Altered gut microbiota composition and function have been associated with inflammatory bowel diseases, including ulcerative colitis (UC), but the causality and mechanisms remain unknown.Methods We applied 16S ribosomal RNA gene sequencing, shotgun metagenomic sequencing, in vitro functional assays, and gnotobiotic colonizations to define the microbial composition and function in fecal samples obtained from a cohort of healthy individuals at risk for inflammatory bowel diseases (pre-UC) who later developed UC (post-UC) and matched healthy control individuals (HCs).Results Microbiota composition of post-UC samples was different from HC and pre-UC samples; however, functional analysis showed increased fecal proteolytic and elastase activity before UC onset. Metagenomics identified more than 22,000 gene families that were significantly different between HC, pre-UC, and post-UC samples. Of these, 237 related to proteases and peptidases, suggesting a bacterial component to the pre-UC proteolytic signature. Elastase activity inversely correlated with the relative abundance of Adlercreutzia and other potentially beneficial taxa and directly correlated with known proteolytic taxa, such as Bacteroides vulgatus. High elastase activity was confirmed in Bacteroides isolates from fecal samples. The bacterial contribution and functional significance of the proteolytic signature were investigated in germ-free adult mice and in dams colonized with HC, pre-UC, or post-UC microbiota. Mice colonized with or born from pre-UC-colonized dams developed higher fecal proteolytic activity and an inflammatory immune tone compared with HC-colonized mice.Conclusions We have identified increased fecal proteolytic activity that precedes the clinical diagnosis of UC and associates with gut microbiota changes. This proteolytic signature may constitute a noninvasive biomarker of inflammation to monitor at-risk populations that can be targeted therapeutically with antiproteases.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
In a longitudinal cohort of ulcerative colitis patients, increased fecal proteolytic activity was seen even prior to disease onset.
“In a longitudinal cohort of UC patients, it was found that increased fecal proteolytic activity was seen in UC patients, even prior to disease onset.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [32]
Transfer of fecal microbiota from ulcerative colitis patients prior to disease onset into mice increased fecal proteolytic activity in the colon and activation of host inflammatory responses.
“Importantly, transfer of fecal microbiota from UC patients prior to disease onset into mice increased fecal proteolytic activity in the colon and activation of host inflammatory responses.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [32]
A bacterial source of fecal proteolytic activity in ulcerative colitis was suggested by detection of an increase in bacterial protease gene expression by shotgun metagenomics.
“A bacterial source of this fecal proteolytic activity was suggested due to detection of an increase in bacterial protease gene expression by shotgun metagenomics.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [32]
Fecal elastase-like activity is increased in ulcerative colitis patients.
“Authors also found an increase in fecal elastase-like activity in UC patients.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [32]
Elastase-like activity is positively correlated with the relative abundance of Bacteroides vulgatus in ulcerative colitis patients.
“Elastase-like activity was positively correlated with the relative abundance of Bacteroides vulgatus, a taxon known to have high proteolytic activity.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [32]
Cites
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
DADA2: High–resolution sample inference from Illumina amplicon data
Callahan, B. J., McMurdie, P. J., Rosen, M. J., Han, A. W., Johnson, A. J. A., & Holmes, S. P. (2016) · Nature Methods · doi:10.1038/nmeth.3869 · Cited by 35,698 · see citing works
Cutadapt removes adapter sequences from high-throughput sequencing reads
Martin, M. (2011) · EMBnet.journal · doi:10.14806/ej.17.1.200 · Cited by 33,889 · see citing works
fastp: an ultra-fast all-in-one FASTQ preprocessor
(2018) · doi:10.1093/bioinformatics/bty560 · Cited by 29,721 · see citing works
Metagenomic biomarker discovery and explanation
Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W. S., & Huttenhower, C. (2011) · Genome Biology · doi:10.1186/gb-2011-12-6-r60 · Cited by 16,192 · see citing works
Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms
Caporaso, J. G., Lauber, C. L., Walters, W. A., Berg-Lyons, D., Huntley, J., Fierer, N., Owens, S. M., Betley, J., Fraser, L., Bauer, M., et al. (2012) · The ISME Journal · doi:10.1038/ismej.2012.8 · Cited by 8,839 · see citing works
Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases
Lloyd-Price, J., Arze, C., Ananthakrishnan, A. N., Schirmer, M., Avila-Pacheco, J., Poon, T. W., Andrews, E., Ajami, N. J., Bonham, K. S., Brislawn, C. J., et al. (2019) · Nature · doi:10.1038/s41586-019-1237-9 · Cited by 3,143 · see citing works
Self-citationBacteroides : the Good, the Bad, and the Nitty-Gritty
Wexler, H. M. (2007) · Clinical Microbiology Reviews · doi:10.1128/cmr.00008-07 · Cited by 2,318 · see citing works
Plovier, H., Everard, A., Druart, C., Depommier, C., Van Hul, M., Geurts, L., Chilloux, J., Ottman, N., Duparc, T., Lichtenstein, L., et al. (2017) · Nature Medicine · doi:10.1038/nm.4236 · Cited by 2,204 · see citing works
How colonization by microbiota in early life shapes the immune system
Gensollen, T., Iyer, S. S., Kasper, D. L., & Blumberg, R. S. (2016) · Science · doi:10.1126/science.aad9378 · Cited by 2,044 · see citing works
Gut microbiome structure and metabolic activity in inflammatory bowel disease
Franzosa, E. A., Sirota-Madi, A., Avila-Pacheco, J., Fornelos, N., Haiser, H. J., Reinker, S., Vatanen, T., Hall, A. B., Mallick, H., McIver, L. J., et al. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0306-4 · Cited by 1,995 · see citing works
Gut microbiota and IBD: causation or correlation?
Ni, J., Wu, G. D., Albenberg, L., & Tomov, V. T. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.88 · Cited by 1,778 · see citing works
Metagenomic microbial community profiling using unique clade-specific marker genes
Segata, N., Waldron, L., Ballarini, A., Narasimhan, V., Jousson, O., & Huttenhower, C. (2012) · Nature Methods · doi:10.1038/nmeth.2066 · Cited by 1,776 · see citing works
Lamas, B., Richard, M. L., Leducq, V., Pham, H.-P., Michel, M.-L., Da Costa, G., Bridonneau, C., Jegou, S., Hoffmann, T. W., Natividad, J. M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4102 · Cited by 1,482 · see citing works
Fungal microbiota dysbiosis in IBD
Sokol, H., Leducq, V., Aschard, H., Pham, H., Jégou, S., Landman, C., Cohen, D., Liguori, G., Bourrier, A., Nion–Larmurier, I., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310746 · Cited by 1,321 · see citing works
The maternal microbiota drives early postnatal innate immune development
Gomez de Agüero, M., Ganal-Vonarburg, S. C., Fuhrer, T., Rupp, S., Uchimura, Y., Li, H., Steinert, A., Heikenwalder, M., Hapfelmeier, S., Sauer, U., et al. (2016) · Science · doi:10.1126/science.aad2571 · Cited by 1,231 · see citing works
Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome
Abubucker, S., Segata, N., Goll, J. B., Schubert, A. M., Izard, J., Cantarel, B. L., Rodriguez-Mueller, B., Zucker, J., Thiagarajan, M., Henrissat, B., et al. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002358 · Cited by 1,050 · see citing works
Environmental triggers in IBD: a review of progress and evidence
Ananthakrishnan, A. N., Bernstein, C. N., Iliopoulos, D., Macpherson, A., Neurath, M. F., Ali, R. A. R., Vavricka, S. R., & Fiocchi, C. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.136 · Cited by 948 · see citing works
Self-citationA weaning reaction to microbiota is required for resistance to immunopathologies in the adult
Al Nabhani, Z., Dulauroy, S., Marques, R., Cousu, C., Al Bounny, S., Déjardin, F., Sparwasser, T., Bérard, M., Cerf-Bensussan, N., & Eberl, G. (2019) · Immunity · doi:10.1016/j.immuni.2019.02.014 · Cited by 679 · see citing works
Rapid and Noninvasive Metabonomic Characterization of Inflammatory Bowel Disease
Marchesi, J. R., Holmes, E. C., Khan, F. M. A., Kochhar, S., Scanlan, P. D., Shanahan, F., Wilson, I. D., & Wang, Y. (2007) · Journal of Proteome Research · doi:10.1021/pr060470d · Cited by 632 · see citing works
Pittayanon, R., Lau, J. T., Leontiadis, G. I., Tse, F., Yuan, Y., Surette, M., & Moayyedi, P. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.294 · Cited by 623 · see citing works
Self-citationRole for protease activity in visceral pain in irritable bowel syndrome
Cenac, N., Andrews, C. N., Holzhausen, M., Chapman, K., Cottrell, G., Andrade-Gordon, P., Steinhoff, M., Barbara, G., Beck, P., Bunnett, N. W., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29255 · Cited by 591 · see citing works
Self-citationVich Vila, A., Imhann, F., Collij, V., Jankipersadsing, S. A., Gurry, T., Mujagic, Z., Kurilshikov, A., Bonder, M. J., Jiang, X., Tigchelaar, E. F., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aap8914 · Cited by 587 · see citing works
Dynamics of metatranscription in the inflammatory bowel disease gut microbiome
Schirmer, M., Franzosa, E. A., Lloyd‐Price, J., McIver, L. J., Schwager, R., Poon, T. W., Ananthakrishnan, A. N., Andrews, E., Barron, G., Lake, K., et al. (2017) · Nature Microbiology · doi:10.1038/s41564-017-0089-z · Cited by 570 · see citing works
Self-citationBritton, G. J., Contijoch, E. J., Mogno, I., Vennaro, O. H., Llewellyn, S. R., Ng, R., Li, Z., Mortha, A., Merad, M., Das, A., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.12.015 · Cited by 549 · see citing works
Bloom, S. M., Bijanki, V. N., Nava, G. M., Sun, L., Malvin, N. P., Donermeyer, D. L., Dunne, W. M., Allen, P. M., & Stappenbeck, T. S. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.04.009 · Cited by 488 · see citing works
Microbial network disturbances in relapsing refractory Crohn’s disease
Swiss IBD Cohort Investigators, Yılmaz, B., Juillerat, P., Øyås, O., Ramon, C., Bravo, F. D., Franc, Y., Fournier, N., Michetti, P., Mueller, C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0308-z · Cited by 426 · see citing works
Faujan, N. H., Abdulamir, A. S., Fatimah, A. B., Anas, O. M., Shuhaimi, M., Yazid, A. M., & Loong, Y. Y. (2010) · The Open Biochemistry Journal · doi:10.2174/1874091x01004010053 · Cited by 361 · see citing works
Steck, N., Hoffmann, M., Sava, I. G., Kim, S. C., Hahne, H., Tonkonogy, S. L., Mair, K., Krueger, D., Pruteanu, M., Shanahan, F., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.05.035 · Cited by 343 · see citing works
Isoflavones: Anti-Inflammatory Benefit and Possible Caveats
Yu, J., Bi, X., Yu, B., & Chen, D. (2016) · Nutrients · doi:10.3390/nu8060361 · Cited by 294 · see citing works
Schirmer, M., Denson, L. A., Vlamakis, H. C., Franzosa, E. A., Thomas, S., Gotman, N., Rufo, P. A., Baker, S. S., Sauer, C. G., Markowitz, J. F., et al. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.09.009 · Cited by 287 · see citing works
Self-citationShaw, K. A., Bertha, M., Hofmekler, T., Chopra, P., Vatanen, T., Srivatsa, A., Prince, J., Kumar, A., Sauer, C. G., Zwick, M. E., et al. (2016) · Genome Medicine · doi:10.1186/s13073-016-0331-y · Cited by 278 · see citing works
Corruption of Innate Immunity by Bacterial Proteases
Potempa, J., & Pike, R. N. (2008) · Journal of Innate Immunity · doi:10.1159/000181144 · Cited by 277 · see citing works
Food-Grade Bacteria Expressing Elafin Protect Against Inflammation and Restore Colon Homeostasis
Motta, J.-P., Bermúdez-Humarán, L. G., Deraison, C., Martin, L., Rolland, C., Rousset, P., Boue, J., Dietrich, G., Chapman, K., Kharrat, P., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004212 · Cited by 257 · see citing works
Capturing the diversity of the human gut microbiota through culture-enriched molecular profiling
Lau, J. Y. F., Whelan, F., Herath, I., Lee, C., Collins, S. M., Berčík, P., & Surette, M. G. (2016) · Genome Medicine · doi:10.1186/s13073-016-0327-7 · Cited by 219 · see citing works
Self-citationEarley, H., Lennon, G., Balfe, Á., Coffey, J. C., Winter, D. C., & O’Connell, P. R. (2019) · Scientific Reports · doi:10.1038/s41598-019-51878-3 · Cited by 203 · see citing works
Regulation of intestinal permeability: The role of proteases
Spaendonk, H. V., Ceuleers, H., Witters, L., Patteet, E., Joossens, J., Augustyns, K., Lambeir, A., Meester, I. D., Man, J. G. D., & Winter, B. Y. D. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i12.2106 · Cited by 191 · see citing works
Ivanov, D. N., Emonet, C., Foata, F., Affolter, M., Delley, M., Fisseha, M., Blum-Sperisen, S., Kochhar, S., & Arigoni, F. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601678200 · Cited by 170 · see citing works
Determinants of IBD Heritability: Genes, Bugs, and More
Turpin, W., Goethel, A., Bedrani, L., & Croitoru, M. K. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izy085 · Cited by 161 · see citing works
Self-citationCaminero, A., McCarville, J. L., Galipeau, H. J., Deraison, C., Bernier, S. P., Constante, M., Rolland, C., Meisel, M., Murray, J. A., Yu, X. B., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09037-9 · Cited by 139 · see citing works
Self-citationModifying the Protease, Antiprotease Pattern by Elafin Overexpression Protects Mice From Colitis
Motta, J., Magne, L., Descamps, D., Rolland, C., Squarzoni–Dale, C., Rousset, P., Martin, L., Cenac, N., Balloy, V., Huerre, M., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2010.12.050 · Cited by 130 · see citing works
Natividad, J. M., Pinto-Sánchez, M. I., Galipeau, H. J., Jury, J., Jordana, M., Reinisch, W., Collins, S. M., Bercik, P., Surette, M. G., Allen‐Vercoe, E., et al. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000422 · Cited by 119 · see citing works
Self-citationFunctional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease
Denadai-Souza, A., Bonnart, C., Tapias, N. S., Marcellin, M., Gilmore, B., Alric, L., Bonnet, D., Burlet-Schiltz, O., Hollenberg, M. D., Vergnolle, N., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-26282-y · Cited by 91 · see citing works
Characterization of the Serpin-Encoding Gene ofBifidobacterium breve210B
Turroni, F., Foroni, E., Motherway, M. O., Bottacini, F., Giubellini, V., Zomer, A., Ferrarini, A., Delledonne, M., Zhang, Z., van Sinderen, D., et al. (2010) · Applied and Environmental Microbiology · doi:10.1128/aem.02938-09 · Cited by 75 · see citing works
The interplay between microbes and the immune response in inflammatory bowel disease
Goethel, A., Croitoru, K., & Philpott, D. J. (2018) · The Journal of Physiology · doi:10.1113/jp275396 · Cited by 74 · see citing works
Self-citationLibertucci, J., Dutta, U., Kaur, S., Jury, J., Rossi, L., Fontes, M. E., Shajib, M. S., Khan, W. I., Surette, M. G., Verdu, E. F., et al. (2018) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00411.2017 · Cited by 69 · see citing works
Self-citationKeshteli, A. H., Tso, R., Dieleman, L. A., Park, H., Kroeker, K. I., Jovel, J., Gillevet, P. M., Sikaroodi, M., Mandal, R., Fedorak, R. N., et al. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izx070 · Cited by 39 · see citing works
Self-citationSeidelin, J. B., & Nielsen, O. H. (2006) · Apmis · doi:10.1111/j.1600-0463.2006.apm_116.x · Cited by 29 · see citing works
Roncase, E. J., Moon, C., Chatterjee, S., González-Páez, G. E., Craik, C. S., O’Donoghue, A. J., & Wolan, D. W. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.7b00143 · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mills, R. H., Dulai, P. S., Vázquez-Baeza, Y., Sauceda, C., Daniel, N., Gerner, R. R., Batachari, L. E., Malfavon, M., Zhu, Q., Weldon, K., et al. (2022) · Nature Microbiology · doi:10.1038/s41564-021-01050-3 · Cited by 385 · see citing works
Kong, C., Liang, L., Liu, G., Du, L., Yang, Y., Liu, J., Shi, D., Li, X., & Ma, Y. (2023) · Gut · doi:10.1136/gutjnl-2022-327156 · Cited by 254 · see citing works
Recipient factors in faecal microbiota transplantation: one stool does not fit all
Danne, C., Rolhion, N., & Sokol, H. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00441-5 · Cited by 154 · see citing works
Edwinson, A. L., Yang, L., Peters, S., Hanning, N., Jeraldo, P., Jagtap, P., Simpson, J. B., Yang, T.-Y., Kumar, P., Mehta, S., et al. (2022) · Nature Microbiology · doi:10.1038/s41564-022-01103-1 · Cited by 105 · see citing works
The emerging roles of bacterial proteases in intestinal diseases
Caminero, A., Guzman, M., Libertucci, J., & Lomax, A. E. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2181922 · Cited by 92 · see citing works
Self-citation
- Authors
- Galipeau, H. J., Caminero, A., Turpin, W., Bermudez-Brito, M., Santiago, A., Libertucci, J., Constante, M., Raygoza Garay, J. A., Rueda, G., Armstrong, S., Clarizio, A., Smith, M. I., Surette, M. G., Bercik, P., Beck, P., Bernstein, C., Croitoru, K., Dieleman, L., Feagan, B., Griffiths, A., Guttman, D., Jacobson, K., Kaplan, G., Krause, D. O., Madsen, K., Marshall, J., Moayyedi, P., Ropeleski, M., Seidman, E., Silverberg, M., Snapper, S., Stadnyk, A., Steinhart, H., Surette, M., Turner, D., Walters, T., Vallance, B., Aumais, G., Bitton, A., Cino, M., Critch, J., Denson, L., Deslandres, C., El-Matary, W., Herfarth, H., Higgins, P., Huynh, H., Hyams, J., Mack, D., McGrath, J., Otley, A., Panancionne, R., Croitoru, K., & Verdu, E. F.
- Affiliations
- McMaster University (CA)
- Mount Sinai Hospital (CA)
- Corresponding author
- Verdu, Elena F.
- ORCID
- Galipeau, Heather J.
- Caminero, Alberto
- Turpin, Williams
- Santiago, Alba
- Libertucci, Josie
- Constante, Marco
- Rueda, Gaston
- Beck, Paul
- Bernstein, Charles
- Feagan, Brian
- Griffiths, Anne
- Guttman, David
- Jacobson, Kevan
- Kaplan, Gilaad
- Madsen, Karen
- Marshall, John
- Moayyedi, Paul
- Seidman, Ernest
- Silverberg, Mark
- Snapper, Scott
- Turner, Dan
- Walters, Thomas
- Vallance, Bruce
- Aumais, Guy
- Bitton, Alain
- Denson, Lee
- Deslandres, Colette
- Herfarth, Hans
- Higgins, Peter
- Huynh, Hien
- Mack, David
- Otley, Anthony
- Verdu, Elena F.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 160
- Issue
- 5
- Pages
- 1532-1545
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W3112205867
- Cited by
- 190
- References
- 49
- Citations by year
- 2026: 23 · 2025: 41 · 2024: 37 · 2023: 33 · 2022: 37 · 2021: 19
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (CMF108031)
- Canadian Association of Gastroenterology
- Canada Foundation for Innovation
- Leona M. and Harry B. Helmsley Charitable Trust
- University of Toronto
- McMaster University
- Government of Ontario
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Epidemiology › Microscopic Colitis
- Keywords
- ulcerative colitis, fecal biomarkers, gut microbiota, proteolytic activity, elastase activity, inflammatory bowel disease, Adlercreutzia, Bacteroides vulgatus, germ-free mice, non-invasive biomarkers, antiprotease therapy, microbial gene function
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Adolescent, Adult, Animals, Bacteria, Bacterial Proteins, Child, Colitis, Ulcerative, Disease Models, Animal, Feces, Female, Germ-Free Life, Humans, Male, Mice, Inbred C57BL, Peptide Hydrolases, Predictive Value of Tests, Prospective Studies, Protease Inhibitors, Reproducibility of Results, Biomarkers, Case-Control Studies, Ribotyping, Mice, Metagenome, Young Adult, Metagenomics, Proteolysis
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
