Diurnal rhythms in the human urine metabolome during sleep and total sleep deprivation
Open accessAbstract
Understanding how metabolite levels change over the 24 hour day is of crucial importance for clinical and epidemiological studies. Additionally, the association between sleep deprivation and metabolic disorders such as diabetes and obesity requires investigation into the links between sleep and metabolism. Here, we characterise time-of-day variation and the effects of sleep deprivation on urinary metabolite profiles. Healthy male participants (n = 15) completed an in-laboratory study comprising one 24 h sleep/wake cycle prior to 24 h of continual wakefulness under highly controlled environmental conditions. Urine samples were collected over set 2–8 h intervals and analysed by 1 H NMR spectroscopy. Significant changes were observed with respect to both time of day and sleep deprivation. Of 32 identified metabolites, 7 (22%) exhibited cosine rhythmicity over at least one 24 h period; 5 exhibiting a cosine rhythm on both days. Eight metabolites significantly increased during sleep deprivation compared with sleep (taurine, formate, citrate, 3-indoxyl sulfate, carnitine, 3-hydroxyisobutyrate, TMAO and acetate) and 8 significantly decreased (dimethylamine, 4-DTA, creatinine, ascorbate, 2-hydroxyisobutyrate, allantoin, 4-DEA, 4-hydroxyphenylacetate). These data indicate that sampling time, the presence or absence of sleep and the response to sleep deprivation are highly relevant when identifying biomarkers in urinary metabolic profiling studies.
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?
One study used NMR to assess urine metabolites in short-term sleep deprivation.
“while one study used NMR to assess urine metabolites in short-term sleep deprivation24”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [24]
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
HMDB 3.0—The Human Metabolome Database in 2013
Wishart, D. S., Jewison, T., Guo, A. C., Wilson, M., Knox, C., Liu, Y., Djoumbou-Feunang, Y., Mandal, R., Aziat, F., Dong, E., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1065 · Cited by 2,845 · see citing works
Adverse metabolic and cardiovascular consequences of circadian misalignment
Scheer, F. A. J. L., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808180106 · Cited by 2,351 · see citing works
Cappuccio, F. P., Cooper, D., D'Elia, L., Strazzullo, P., & Miller, M. A. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr007 · Cited by 2,146 · see citing works
Dieterle, F., Ross, A., Schlotterbeck, G., & Senn, H. (2006) · Analytical Chemistry · doi:10.1021/ac051632c · Cited by 1,772 · see citing works
Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes
Spiegel, K., Knutson, K., Leproult, R., Tasali, E., & Cauter, E. V. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00660.2005 · Cited by 1,175 · see citing works
Bennett, B. J., Vallim, T. Q. D. A., Wang, Z., Shih, D. M., Meng, Y., Gregory, J., Allayee, H., Lee, R., Graham, M., Crooke, R., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.011 · Cited by 1,070 · see citing works
Human metabolic phenotype diversity and its association with diet and blood pressure
Holmes, E., Loo, R. L., Stamler, J., Bictash, M., Yap, I. K. S., Chan, Q., Ebbels, T., De Iorio, M., Brown, I. J., Veselkov, K. A., et al. (2008) · Nature · doi:10.1038/nature06882 · Cited by 1,054 · see citing works
Normal and Pathologic Concentrations of Uremic Toxins
Duranton, F., Cohen, G., Smet, R. D., Rodríguez, M., Jankowski, J., Vanholder, R. C., & Argilés, À. (2012) · Journal of the American Society of Nephrology · doi:10.1681/asn.2011121175 · Cited by 965 · see citing works
Barreto, F. C., Barreto, D. V., Liabeuf, S., Meert, N., Glorieux, G., Temmar, M., Choukroun, G. J., Vanholder, R. C., & Massy, Z. A. (2009) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.03980609 · Cited by 932 · see citing works
Cloarec, O., Dumas, M., Craig, A., Barton, R. H., Trygg, J., Hudson, J., Blancher, C., Gauguier, D., Lindon, J. C., Holmes, E. C., et al. (2005) · Analytical Chemistry · doi:10.1021/ac048630x · Cited by 912 · see citing works
Clayton, T. A., Baker, D., Lindon, J. C., Everett, J. R., & Nicholson, J. K. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904489106 · Cited by 765 · see citing works
The Uremic Toxicity of Indoxyl Sulfate and p-Cresyl Sulfate
Vanholder, R. C., Schepers, E., Pletinck, A., Nagler, E., & Glorieux, G. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013101062 · Cited by 684 · see citing works
Serotonin control of sleep-wake behavior
Monti, J. M. (2011) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2010.11.003 · Cited by 614 · see citing works
The human circadian metabolome
Dallmann, R., Viola, A. U., Tarokh, L., Cajochen, C., & Brown, S. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114410109 · Cited by 566 · see citing works
Dona, A. C., Jiménez, B., Schäfer, H., Humpfer, E., Spraul, M., Lewis, M. R., Pearce, J. T. M., Holmes, E., Lindon, J. C., & Nicholson, J. K. (2014) · Analytical Chemistry · doi:10.1021/ac5025039 · Cited by 540 · see citing works
Effect of sleep deprivation on the human metabolome
Davies, S. K., Ang, J. E., Revell, V. L., Holmes, B., Mann, A., Robertson, F. P., Cui, N., Middleton, B., Ackermann, K., Kayser, M., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402663111 · Cited by 527 · see citing works
Self-citationSlupsky, C. M., Rankin, K. N., Wagner, J., Fu, H., Chang, D., Weljie, A. M., Saude, E. J., Lix, B., Adamko, D. J., Shah, S. L., et al. (2007) · Analytical Chemistry · doi:10.1021/ac0708588 · Cited by 398 · see citing works
Mistimed sleep disrupts circadian regulation of the human transcriptome
Archer, S. N., Laing, E. E., Möller-Levet, C. S., van der Veen, D. R., Bucca, G., Lazar, A. S., Santhi, N., Slak, A., Kabiljo, R., von Schantz, M., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316335111 · Cited by 386 · see citing works
Homer1a is a core brain molecular correlate of sleep loss
Maret, S., Dorsaz, S., Gurcel, L., Pradervand, S., Petit, B., Pfister, C., Hagenbüchle, O., O’Hara, B. F., Franken, P., & Tafti, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710131104 · Cited by 366 · see citing works
Veselkov, K., Lindon, J. C., Ebbels, T. M. D., Crockford, D. J., Volynkin, V., Holmes, E. C., Davies, D. B., & Nicholson, J. K. (2008) · Analytical Chemistry · doi:10.1021/ac8011544 · Cited by 338 · see citing works
The gut-kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression
Meijers, B. K. I., & Evenepoel, P. (2011) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfq818 · Cited by 329 · see citing works
O'Sullivan, A., Gibney, M. J., & Brennan, L. (2011) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.000950 · Cited by 297 · see citing works
Sleep and Metabolism: An Overview
Sharma, S., & Kavuru, M. S. (2010) · International Journal of Endocrinology · doi:10.1155/2010/270832 · Cited by 277 · see citing works
Altamura, C., Maes, M., Dai, J., & Meltzer, H. Y. (1995) · European Neuropsychopharmacology · doi:10.1016/0924-977x(95)00033-l · Cited by 193 · see citing works
Tumur, Z., & Niwa, T. (2009) · American Journal of Nephrology · doi:10.1159/000191468 · Cited by 192 · see citing works
Variation of metabolites in normal human urine
Saude, E. J., Adamko, D. J., Rowe, B. H., Marrie, T. J., & Sykes, B. D. (2007) · Metabolomics · doi:10.1007/s11306-007-0091-1 · Cited by 178 · see citing works
Taurine Is a Potent Activator of Extrasynaptic GABA A Receptors in the Thalamus
Jia, F., Yue, M. E., Chandra, D., Keramidas, A., Goldstein, P. A., Homanics, G. E., & Harrison, N. L. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3996-07.2008 · Cited by 171 · see citing works
Human Metabolic Phenotypes Link Directly to Specific Dietary Preferences in Healthy Individuals
Rezzi, S., Ramadan, Z., Martin, F., Fay, L. B., van Bladeren, P., Lindon, J. C., Nicholson, J. K., & Kochhar, S. (2007) · Journal of Proteome Research · doi:10.1021/pr070431h · Cited by 161 · see citing works
Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt
Weljie, A. M., Meerlo, P., Goel, N., Sengupta, A., Kayser, M. S., Abel, T., Birnbaum, M. J., Dinges, D. F., & Sehgal, A. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417432112 · Cited by 158 · see citing works
A new method for absolute quantitation MRS metabolites
Barantin, L., Pape, A. L., & Akoka, S. (1997) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910380203 · Cited by 157 · see citing works
Hereditary Mental Depression and Parkinsonism With Taurine Deficiency
Perry, T. L., Bratty, P. J. A., Hansen, S., Kennedy, J. L., Urquhart, N., & Dolman, C. L. (1975) · Archives of Neurology · doi:10.1001/archneur.1975.00490440058009 · Cited by 141 · see citing works
Ackermann, K., Revell, V. L., Lao, O., Rombouts, E. J., Skene, D. J., & Kayser, M. (2012) · Sleep · doi:10.5665/sleep.1954 · Cited by 129 · cited 1× · see citing works
“[16] with permission.”
Self-citationMoolenaar, S. H., Engelke, U. F. H., & Wevers, R. A. (2003) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1258/000456303321016132 · Cited by 121 · see citing works
Effect of sleep deprivation on rhythms of clock gene expression and melatonin in humans
Ackermann, K., Plomp, R., Lao, O., Middleton, B., Revell, V. L., Skene, D. J., & Kayser, M. (2013) · Chronobiology International · doi:10.3109/07420528.2013.784773 · Cited by 116 · see citing works
Self-citationIndoxyl Sulfate and Atherosclerotic Risk Factors in Hemodialysis Patients
Taki, K., Tsuruta, Y., & Niwa, T. (2007) · American Journal of Nephrology · doi:10.1159/000098542 · Cited by 112 · see citing works
Maher, A. D., Zirah, S., Holmes, E. C., & Nicholson, J. K. (2007) · Analytical Chemistry · doi:10.1021/ac070212f · Cited by 112 · see citing works
Bass, J. T., & Turek, F. W. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.1.15 · Cited by 99 · see citing works
Metabolic rate and fuel utilization during sleep assessed by whole-body indirect calorimetry
Katayose, Y., Tasaki, M., Ogata, H., Nakata, Y., Tokuyama, K., & Satoh, M. (2009) · Metabolism · doi:10.1016/j.metabol.2009.02.025 · Cited by 95 · see citing works
Maître, L., Fthenou, E., Athersuch, T. J., Coen, M., Toledano, M. B., Holmes, E. C., Kogevinas, M., Chatzi, L., & Keun, H. C. (2014) · BMC Medicine · doi:10.1186/1741-7015-12-110 · Cited by 95 · see citing works
Self-citationFujii, H., Nakai, K., & Fukagawa, M. (2011) · Therapeutic Apheresis and Dialysis · doi:10.1111/j.1744-9987.2010.00883.x · Cited by 94 · see citing works
The sleep relay—the role of the thalamus in central and decentral sleep regulation
Coulon, P., Budde, T., & Pape, H. (2011) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-011-1014-6 · Cited by 86 · see citing works
Following Healthy Pregnancy by Nuclear Magnetic Resonance (NMR) Metabolic Profiling of Human Urine
Diaz, S. O., Barros, A. S., Goodfellow, B. J., Duarte, I. F., Carreira, I. M., Galhano, E. M. B., Pita, C., Almeida, M. D. C., & Gil, A. M. (2012) · Journal of Proteome Research · doi:10.1021/pr301022e · Cited by 57 · see citing works
Identification of 4-deoxythreonic acid present in human urine using HPLC and NMR techniques
Appiah‐Amponsah, E., Shanaiah, N., Gowda, G. A. N., Owusu-Sarfo, K., Ye, T., & Raftery, D. (2009) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2009.06.007 · Cited by 37 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Quality assurance procedures for mass spectrometry untargeted metabolomics. a review
Dudzik, D., Barbas-Bernardos, C., Garcı́a, A., & Barbas, C. (2017) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2017.07.044 · Cited by 346 · see citing works
Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks
Dyar, K. A., Lutter, D., Artati, A., Ceglia, N., Liu, Y., Armenta, D., Jastroch, M., Schneider, S., de Mateo, S., Cervantes, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.042 · Cited by 335 · see citing works
“Providing essential temporal perspective, several groups have begun mapping metabolite dynamics over 24 hr (Aviram et al., 2016; Chen et al., 2016; Dallmann et al., 2012; Davies et al., 2014; Dyar et al., 2013; Eckel-Mahan et al., 2012; Fustin et al., 2012; Giskeødegård et al., 2015; Kim et al., 2014; Krishnaiah et al…”
BackgroundBallesta, A., Innominato, P. F., Dallmann, R., Rand, D. A. J., & Lévi, F. (2017) · Pharmacological Reviews · doi:10.1124/pr.116.013441 · Cited by 342 · see citing works
Dosing-Time Makes the Poison: Circadian Regulation and Pharmacotherapy
Dallmann, R., Okyar, A., & Lévi, F. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.03.004 · Cited by 295 · see citing works
Potential Role for the Gut Microbiota in Modulating Host Circadian Rhythms and Metabolic Health
Parkar, S. G., Kalsbeek, A., & Cheeseman, J. F. (2019) · Microorganisms · doi:10.3390/microorganisms7020041 · Cited by 285 · see citing works
“For example, acetate and 3-indoxyl sulfate, trimethylamine-N-oxide, p-cresol sulfate, and 3-hydroxyisobutyrate (generated by microbial breakdown of tryptophan, choline, tyrosine and valine respectively) [46].”
BackgroundCompartmentalised acyl-CoA metabolism and roles in chromatin regulation
Trefely, S., Lovell, C. D., Snyder, N. W., & Wellen, K. E. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.005 · Cited by 272 · see citing works
“2-HIB levels in urine were increased in obesity in humans [163e165], decreased in sleep deprivation in humans [166], and varied according to gender in obese mouse models [167].”
BackgroundFeeding Rhythms and the Circadian Regulation of Metabolism
Pickel, L., & Sung, H. (2020) · Frontiers in Nutrition · doi:10.3389/fnut.2020.00039 · Cited by 261 · see citing works
“Alternatives to plasma for noninvasive serial sampling include urine (184) and breath.”
BackgroundTrimethylamine <i>N</i>-oxide and prognosis in acute heart failure
Suzuki, T., Heaney, L. M., Bhandari, S. S., Jones, D. J. L., & Ng, L. L. (2016) · Heart · doi:10.1136/heartjnl-2015-308826 · Cited by 253 · see citing works
Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism
Krishnaiah, S., Wu, G., Altman, B. J., Growe, J., Rhoades, S. D., Coldren, F., Venkataraman, A., Olarerin-George, A. O., Francey, L. J., Mukherjee, S., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.019 · Cited by 207 · see citing works
Kervezee, L., Kosmadopoulos, A., & Boivin, D. B. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14216 · Cited by 216 · see citing works
Kirwan, J., Brennan, L., Broadhurst, D., Fiehn, O., Cascante, M., Dunn, W. B., Schmidt, M. A., & Velagapudi, V. (2018) · Clinical Chemistry · doi:10.1373/clinchem.2018.287045 · Cited by 171 · see citing works
Redox changes in obesity, metabolic syndrome, and diabetes
Korać, B., Kalezic, A., Pekovic‐Vaughan, V., Korać, A., & Janković, A. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101887 · Cited by 162 · see citing works
“Previous work has characterized ~24h time-of-day variation and the effects of sleep deprivation on urinary metabolite profiles in healthy male participants under highly controlled environmental conditions by 1H NMR spectroscopy [166].”
BackgroundMolecular Mechanisms of Sleep Homeostasis in Flies and MammalsPreprint
Allada, R., Cirelli, C., & Sehgal, A. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a027730 · Cited by 155 · see citing works
Metabolomics in the study of retinal health and disease
Laíns, I., Gantner, M., Murinello, S., Lasky-Su, J. A., Miller, J. W., Friedlander, M., & Husain, D. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.11.002 · Cited by 150 · see citing works
Pezzatti, J., Boccard, J., Codesido, S., Gagnebin, Y., Joshi, A., Picard, D., González‐Ruiz, V., & Rudaz, S. L. (2020) · Analytica Chimica Acta · doi:10.1016/j.aca.2019.12.062 · Cited by 152 · see citing works
Cedernaes, J., Schönke, M., Westholm, J. O., Mi, J., Chibalin, A., Voisin, S., Osler, M., Vogel, H., Hörnaeus, K., Dickson, S. L., et al. (2018) · Science Advances · doi:10.1126/sciadv.aar8590 · Cited by 137 · see citing works
Ma, W., Song, J., Wang, H., Shi, F., Zhou, N., Jiang, J., Xu, Y., Zhang, L., Yang, L., & Zhou, M. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.04.006 · Cited by 134 · see citing works
Metabolomics in Sleep, Insomnia and Sleep Apnea
Humer, E. C., Pieh, C., & Brandmayr, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197244 · Cited by 133 · see citing works
“Humans Urine NMR 2 Taurine, formate, citrate, 3-indoxyl sulfate, carnitine, 3-hydroxyisobutyrate, trimethylamine-N-oxide, acetate, dimethylamine, 4-deoxythreonic acid, creatinine, ascorbate, 2-hydroxyisobutyrate, allantoin, 4-deoxyeryhtronic acid, 4-hydroxyphenylacetate Neurotransmitter metabolism, fatty acid metaboli…”
BackgroundAho, V., Ollila, H. M., Kronholm, E., Bondia-Pons, I., Soininen, P., Kangas, A. J., Hilvo, M., Seppälä, I., Kettunen, J., Oikonen, M., et al. (2016) · Scientific Reports · doi:10.1038/srep24828 · Cited by 126 · see citing works
Praveenraj, S. S., Sonali, S., Anand, N., Hediyal, T. A., Vichitra, C., Kalyan, M., Kanna, P. V., Chandana, K. A., Paneyala, S., Mahalakshmi, A. M., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02990-5 · Cited by 111 · see citing works
Köhler, I., Hankemeier, T., van der Graaf, P. H., Knibbe, C. A. J., & van Hasselt, J. G. C. (2017) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2017.05.018 · Cited by 107 · see citing works
“Patient-specific characteristics may vary not only between but also within patients over short periods of time; and include for instance circadian rhythms (Giskeodegard et al. 2015) or the menstrual cycle (Wallace et al. 2010).”
BackgroundLoizides‐Mangold, U., Perrin, L., Vandereycken, B., Betts, J. A., Walhin, J., Templeman, I., Chanon, S., Weger, B. D., Durand, C., Robert, M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705821114 · Cited by 104 · see citing works
Collection and Preparation of Clinical Samples for Metabolomics
Chetwynd, A. J., Dunn, W. B., & Blanco, G. R. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-47656-8_2 · Cited by 99 · see citing works
Coupled network of the circadian clocks: a driving force of rhythmic physiology
Finger, A., Dibner, C., & Kramer, A. (2020) · FEBS Letters · doi:10.1002/1873-3468.13898 · Cited by 99 · see citing works
Melatonin: Countering Chaotic Time Cues
Arendt, J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00391 · Cited by 89 · see citing works
“Following sleep deprivation it was clear that many metabolites desynchronized amongst themselves (163, 164).”
BackgroundEffects of meal timing on postprandial glucose metabolism and blood metabolites in healthy adults
Takahashi, M., Ozaki, M., Kang, M.-I., Sasaki, H., Fukazawa, M., Iwakami, T., Lim, P. J., Kim, H.-K., Aoyama, S., & Shibata, S. (2018) · Nutrients · doi:10.3390/nu10111763 · Cited by 81 · see citing works
“In fact, the blood, urine and saliva human metabolomes were found to differ between morning and evening under both free-living and experimental conditions [22,23,28].”
BackgroundUrinary Biomarkers and Their Potential for the Non-Invasive Detection of Endometrial Cancer
Njoku, K., Chiasserini, D., Jones, E. R., Barr, C. E., O’Flynn, H., Whetton, A. D., & Crosbie, E. J. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.559016 · Cited by 78 · see citing works
“Levels of several urinary metabolites also exhibit a circadian rhythm (76).”
BackgroundThe key points in the pre-analytical procedures of blood and urine samples in metabolomics studies
Bi, H., Guo, Z., Jia, X., Liu, H., Ma, L., & Xue, L. (2020) · Metabolomics · doi:10.1007/s11306-020-01666-2 · Cited by 76 · see citing works
Schugar, R. C., Gliniak, C. M., Osborn, L. J., Massey, W. J., Sangwan, N., Horak, A. J., Banerjee, R., Orabi, D., Helsley, R. N., Brown, A. L., et al. (2022) · eLife · doi:10.7554/elife.63998 · Cited by 73 · see citing works
Metabolomics Profiling for Obstructive Sleep Apnea and Simple Snorers
Xu, H., Zheng, X., Qian, Y., Guan, J., Yi, H., Zou, J., Wang, Y., Meng, L., Zhao, A., Yin, S., et al. (2016) · Scientific Reports · doi:10.1038/srep30958 · Cited by 73 · see citing works
Awwad, H. M., Geisel, J., & Obeid, R. (2016) · Journal of Chromatography B · doi:10.1016/j.jchromb.2016.10.017 · Cited by 73 · see citing works
Multivariate analysis of NMR‐based metabolomic data
Debik, J., Sangermani, M., Wang, F., Madssen, T. S., & Giskeødegård, G. F. (2021) · NMR in Biomedicine · doi:10.1002/nbm.4638 · Cited by 74 · see citing works
Self-citationLiu, X., Cheng, X., Liu, X., He, L., Zhang, W., Wang, Y., Sun, W., & Ji, Z. (2018) · International Journal of Cancer · doi:10.1002/ijc.31323 · Cited by 70 · see citing works
Balancing the Equation: A Natural History of Trimethylamine and Trimethylamine-N-oxide
Loo, R. L., Chan, Q. M., Nicholson, J. K., & Holmes, E. C. (2022) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00851 · Cited by 60 · see citing works
Glucose Homeostasis: Regulation by Peripheral Circadian Clocks in Rodents and Humans
Gachon, F., Loizides‐Mangold, U., Petrenko, V., & Dibner, C. (2017) · Endocrinology · doi:10.1210/en.2017-00218 · Cited by 63 · see citing works
A systems genetics resource and analysis of sleep regulation in the mouse
Diessler, S., Jan, M., Emmenegger, Y., Guex, N., Middleton, B., Skene, D. J., Ibberson, M. R., Burdet, F., Götz, L., Pagni, M., et al. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2005750 · Cited by 61 · see citing works
Self-citationThe Taurine Transporter Eaat2 Functions in Ensheathing Glia to Modulate Sleep and Metabolic Rate
Stahl, B. A., Peco, E., Davla, S., Murakami, K., Moreno, N. A. C., van Meyel, D. J., & Keene, A. C. (2018) · Current Biology · doi:10.1016/j.cub.2018.10.039 · Cited by 59 · see citing works
Burton, C., & Ma, Y. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867324666170914102236 · Cited by 59 · see citing works
Circadian and Sleep Metabolomics Across Species
Malik, D. M., Paschos, G. K., Sehgal, A., & Weljie, A. M. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.04.027 · Cited by 52 · see citing works
Bourdon, A. K., Spano, G. M., Marshall, W., Bellesi, M., Tononi, G., Serra, P. A., Baghdoyan, H. A., Lydic, R., Campagna, S. R., & Cirelli, C. (2018) · Scientific Reports · doi:10.1038/s41598-018-29511-6 · Cited by 54 · see citing works
Chronical sleep interruption-induced cognitive decline assessed by a metabolomics method
Li, F., Wu, H., Song, G., Lü, C., Li, Y., Qu, L., Chen, S.-G., Liu, X., & Chang, Q. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.12.039 · Cited by 51 · see citing works
Khamaysi, A., Anbtawee-Jomaa, S., Fremder, M., Eini-Rider, H., Shimshilashvili, L., Aharon, S., Aizenshtein, E., Shlomi, T., Noguchi, A. C., Springer, D., et al. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2018030277 · Cited by 51 · see citing works
Circadian Metabolomics in Time and Space
Dyar, K. A. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00369 · Cited by 50 · see citing works
“In a similar study comparing the effects of sleep deprivation on a smaller group of metabolites obtained from human urine, 22% of metabolites were observed to be rhythmic, either under normal or sleep-deprived conditions (Giskeodegard et al., 2015).”
BackgroundEffects of inter-day and intra-day variation on salivary metabolomic profiles
Kawanishi, N., Hoshi, N., Sugimoto, M., Enomoto, A., Ota, S., Kaneko, M., Soga, T., Tomita, M., & Kimoto, K. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.11.030 · Cited by 49 · see citing works
The importance of being rhythmic: Living in harmony with your body clocks
Dibner, C. (2019) · Acta Physiologica · doi:10.1111/apha.13281 · Cited by 45 · see citing works
Grant, L. K., Ftouni, S., Nijagal, B., Souza, D. P. D., Tull, D., McConville, M. J., Rajaratnam, S. M. W., Lockley, S. W., & Anderson, C. (2019) · Scientific Reports · doi:10.1038/s41598-019-40353-8 · Cited by 46 · see citing works
Metabolomics in asthma: A platform for discovery
Xu, S., Panettieri, R. A., & Jude, J. A. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.100990 · Cited by 43 · see citing works
Circadian rhythm of lipid metabolism
Sinturel, F., Spaleniak, W., & Dibner, C. (2022) · Biochemical Society Transactions · doi:10.1042/bst20210508 · Cited by 41 · see citing works
Circadian- and Light-driven Metabolic Rhythms in Drosophila melanogaster
Rhoades, S. D., Nayak, K., Zhang, S., Sehgal, A., & Weljie, A. M. (2018) · Journal of Biological Rhythms · doi:10.1177/0748730417753003 · Cited by 39 · see citing works
“…WT-LD 20- to 28-h cyclers in our study to oscillate in other species, including zebrafish, mice, and humans (Li et al., 2015; Zwigahft et al., 2015; Giskeødegård et al., 2015; Davies et al., 2014; Chaix et al., 2014; Hatori et al., 2012; Eckel-Mahan et al., 2012; Dallmann et al., 2012; Ang…”
Sleep restriction induced energy, methylation and lipogenesis metabolic switches in rat liver
Sengupta, A., Rhoades, S. D., Kim, E. J., Nayak, S., Grant, G. R., Meerlo, P., & Weljie, A. M. (2017) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.08.014 · Cited by 35 · see citing works
Assessment of metabolic phenotypic variability in children’s urine using 1H NMR spectroscopy
Maître, L., Lau, C. E., Vizcaíno, E., Robinson, O., Casas, M., Siskos, A., Want, E. J., Athersuch, T. J., Slama, R., Vrijheid, M., et al. (2017) · Scientific Reports · doi:10.1038/srep46082 · Cited by 34 · see citing works
Self-citationSalivary metabolomics for cancer detection
Sugimoto, M. (2020) · Expert Review of Proteomics · doi:10.1080/14789450.2020.1846524 · Cited by 32 · see citing works
Hancox, T. P. M., Skene, D. J., Dallmann, R., & Dunn, W. B. (2021) · Metabolites · doi:10.3390/metabo11050328 · Cited by 33 · see citing works
“[85], followed by several others [86,87] (see Tables 3 and S3).”
BackgroundMethodResultInfluentialSelf-citationYoon, S. J., Long, N. P., Jung, K.-H., Kim, H. M., Hong, Y. J., Fang, Z., Kim, S. J., Kim, T., Anh, N. H., Hong, S., et al. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00234 · Cited by 31 · see citing works
Kusonmano, K., Vongsangnak, W., & Chumnanpuen, P. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-1503-8_5 · Cited by 30 · see citing works
A Unified Conceptual Framework for Metabolic Phenotyping in Diagnosis and Prognosis
Everett, J. R., Holmes, E. C., Veselkov, K., Lindon, J. C., & Nicholson, J. K. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.08.004 · Cited by 31 · see citing works
“Whilst there are well-documented procedures for sample preparation for both NMR-[29,30] and MS-based metabolic phenotyping approaches,[31],[32] it is now well known that diet, drug-taking and diurnal variation,[33] as well as factors such as gender and age, will all affect the metabolite profiles obtained and several…”
Enhancing cosinor analysis of circadian phase markers using the gamma distribution
Doyle, M., Murphy, T. E., Miner, B., Pisani, M. A., Lusczek, E. R., & Knauert, M. P. (2022) · Sleep Medicine · doi:10.1016/j.sleep.2022.01.015 · Cited by 26 · see citing works
Russell, K. L., Rodman, H. R., & Pak, V. M. (2023) · Sleep And Breathing · doi:10.1007/s11325-023-02828-x · Cited by 27 · see citing works
“Formate Formate exhibited the largest increase in concentration during sleep deprivation [39].”
BackgroundResultInfluentialSystems Biology-Derived Discoveries of Intrinsic Clocks
Millius, A., & Ueda, H. R. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00025 · Cited by 26 · see citing works
Gordon-Dseagu, V., Derkach, A., Xiao, Q., Williams, I., Sampson, J. N., & Stolzenberg‐Solomon, R. Z. (2019) · Metabolomics · doi:10.1007/s11306-019-1472-y · Cited by 24 · see citing works
Broughton‐Neiswanger, L. E., Rivera, S. M., Suarez, M. A., Slovak, J. E., Piñeyro, P. E., Hwang, J. K., & Villarino, N. F. (2020) · PLoS ONE · doi:10.1371/journal.pone.0228989 · Cited by 22 · see citing works
“Many extrinsic factors have been shown to affect the urinary metabolome including the gastrointestinal microbiota [57], [58], obesity/diet [59], [60], age [61], exercise [62], diurnal variation [63], gender [61], and environmental chemicals [64].”
BackgroundLiu, W., Zhao, D., Wu, X., Yue, F., Yang, H., & Hu, K. (2022) · Bioengineered · doi:10.1080/21655979.2022.2037872 · Cited by 24 · see citing works
The effect of sampling procedures and day-to-day variations in metabolomics studies of biofluids
Giskeødegård, G. F., Andreassen, T., Bertilsson, H., Tessem, M., & Bathen, T. F. (2019) · Analytica Chimica Acta · doi:10.1016/j.aca.2019.07.026 · Cited by 25 · see citing works
Self-citationDetection of Inflammation via Volatile Cues in Human Urine
Gordon, A. R., Kimball, B., Sorjonen, K., Karshikoff, B., Axelsson, J., Lekander, M., Lundström, J., & Olsson, M. (2018) · Chemical Sensors · doi:10.1093/chemse/bjy059 · Cited by 20 · see citing works
“1989) and that a significant proportion of the human urine metabolome exhibits a diurnal rhythm (Giskeødegård et al. 2015).”
BackgroundDing, L., & Xiao, X. (2020) · Chinese Medical Journal · doi:10.1097/cm9.0000000000000702 · Cited by 24 · see citing works
A method for comparative metabolomics in urine using high resolution mass spectrometry
Ramakrishnan, P., Nair, S. N., & Rangiah, K. (2016) · Journal of Chromatography A · doi:10.1016/j.chroma.2016.02.080 · Cited by 22 · see citing works
Williamson, G., & Clifford, M. N. (2024) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2024.2410874 · Cited by 22 · see citing works
Metabolomics reveal circadian control of cellular metabolism
Ch, R., Chevallier, O. P., & Elliott, C. T. (2020) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2020.115986 · Cited by 20 · see citing works
Fritz, J., Huang, T., Depner, C. M., Zeleznik, O. A., Feliciano, E. M. C., Li, W., Stone, K. L., Manson, J. E., Clish, C. B., Sofer, T., et al. (2022) · SLEEP · doi:10.1093/sleep/zsac226 · Cited by 19 · see citing works
Chang, C., Hsu, J.-Y., Su, Y.-H., Chen, Y.-C., Hsiao, P.-Z., & Liao, P. (2023) · Chemosphere · doi:10.1016/j.chemosphere.2023.138864 · Cited by 20 · see citing works
Time is ripe: maturation of metabolomics in chronobiology
Rhoades, S. D., Sengupta, A., & Weljie, A. M. (2016) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2016.09.007 · Cited by 19 · see citing works
Yang, B., Liao, G., Wen, X., Chen, W., Cheng, S., Stolzenburg, J., Ganzer, R., & Neuhaus, J. (2017) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b1600441 · Cited by 17 · see citing works
“Giskeødegård et al. (2015a; 2015b) analyzed blood plasma and serum samples from 29 PCa patients and 21 controls with BPH by a combination of magnetic resonance spectroscopy, MS, and GC.”
MethodMetabolomic Profiling of Human Urine Samples Using LC-TIMS-QTOF Mass Spectrometry
Poto, C. D., Tian, X., Peng, X., Heyman, H. M., Szesny, M., Hess, S. Y., & Cazares, L. H. (2021) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.0c00467 · Cited by 17 · see citing works
Omics Approaches in Sleep-Wake Regulation
O’Callaghan, E. K., Green, E. W., Franken, P., & Mongrain, V. (2018) · Handbook of experimental pharmacology · doi:10.1007/164_2018_125 · Cited by 16 · see citing works
Metabolism of sleep and aging: Bridging the gap using metabolomics
Sengupta, A., & Weljie, A. M. (2018) · Nutrition and Healthy Aging · doi:10.3233/nha-180043 · Cited by 16 · see citing works
“with this, 13 other metabolites were found to 589 be altered including elevated taurine, formate, cit590 rate, 3-hydroxyisobutyrate, TMAO, acetate and 591 decreased dimethylamine, 4-deoxythreonic acid, cre592 atinine, ascorbate, 2-hydroxyisobutyrate, allantoin, 593 4-deoxyerythronic acid and 4-hydroxyphenylacetate 594…”
Zhu, S., Wang, Y., Li, Y., Li, N., Zheng, Y., Li, Q., Guo, H., Sun, J., Zhai, Q., & Zhu, Y. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1499591 · Cited by 15 · see citing works
Makris, K. C. (2021) · BioEssays · doi:10.1002/bies.202100159 · Cited by 14 · see citing works
“[36] From studies using standardized meals, diurnal variation within an individual was detected suggesting systemic contribution to this variation.[32] In urine, five metabolites were identified that”
BackgroundAslibekyan, S. W., Irvin, M. R., Hidalgo, B., Perry, R. T., Jeyarajah, E. J., Garcia, E., SHALAUROVA, I. Y., Hopkins, P. N., Province, M. A., Tiwari, H. K., et al. (2017) · Journal of Nutrition & Intermediary Metabolism · doi:10.1016/j.jnim.2017.03.002 · Cited by 13 · see citing works
Zhang, X., Wang, X., Le, S., Ojanen, X., Tan, X. W., Wiklund, P., & Cheng, S. (2020) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2020.05.002 · Cited by 13 · see citing works
Lau, C. E., Taylor‐Bateman, V., Vorkas, P. A., Graça, G., Vu, T. T., Hou, L., Chekmeneva, E., Ebbels, T. M. D., Chan, Q. M., Horn, L. V., et al. (2020) · Metabolites · doi:10.3390/metabo10120498 · Cited by 11 · see citing works
Metabolomic profiles in night shift workers: A cross-sectional study on hospital female nurses
Borroni, E., Frigerio, G., Polledri, E., Mercadante, R., Maggioni, C., Fedrizzi, L., Pesatori, A. C., Fustinoni, S., & Carugno, M. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1082074 · Cited by 11 · see citing works
Li, X., Li, S., & Kellermann, G. H. (2017) · Journal of Chromatography B · doi:10.1016/j.jchromb.2017.09.049 · Cited by 10 · see citing works
Use of nuclear magnetic resonance spectroscopy in diagnosis of inborn errors of metabolism
Speyer, C. B., & Baleja, J. (2021) · Emerging Topics in Life Sciences · doi:10.1042/etls20200259 · Cited by 10 · see citing works
Influence of Trimethylamine N-Oxide on Platelet Activation
Emonds, J. J., Ringel, C., Reinicke, M., Müller, D., von Eckardstein, A., Meixensberger, J., Ceglarek, U., & Gaudl, A. (2022) · Nutrients · doi:10.3390/nu14163261 · Cited by 9 · see citing works
“rhythmicity [15] of TMAO plasma concentrations have been described.”
MethodThe role of urinary pteridines as disease biomarkers
Burton, C., & Ma, Y. (2017) · Pteridines · doi:10.1515/pterid-2016-0013 · Cited by 10 · see citing works
“demonstrated that sleep deprivation resulting in disrupted circadian rhythms, affected primary and secondary metabolite synthesis and excretion into urine [138].”
BackgroundLiu, J., Xu, Y., Ji, Y., Li, K., Wang, S., Zhao, B., Ruan, J., Foulkes, N. S., Zhang, S., & Zhao, H. (2023) · The Innovation Life · doi:10.59717/j.xinn-life.2023.100037 · Cited by 8 · see citing works
Su, Y.-H., Chang, C., Hsu, J.-Y., Li, S., Sung, P., Wang, R.-H., Wu, C., & Liao, P. (2023) · Molecules · doi:10.3390/molecules28052166 · Cited by 8 · see citing works
Spiegeleer, M. D., Plekhova, V., Geltmeyer, J., Schoolaert, E., Pomian, B., Singh, V., Wijnant, K., Windt, K. D., Paukku, V., Loof, A. D., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade9933 · Cited by 8 · see citing works
Ou, H., Kawaguchi, S., Sonomura, K., Kawaguchi, T., Kitada, S., Yoshiji, S., Brial, F., Gauguier, D., Xia, J., & Matsuda, F. (2023) · Scientific Reports · doi:10.1038/s41598-023-40697-2 · Cited by 7 · see citing works
“Urine 4-CS is decreased in situations of acute sleep deprivation 36 , whereas we observed associations between elevated plasma 4-CS and low sleep quality and increased usage of sleeping pills, suggesting that impaired elimination of 4-CS from plasma to urine may account for modified Table 2.”
Adav, S. S., & Ng, K. W. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01548-4 · Cited by 7 · see citing works
“Biomarker discovery for AD typically relies on plasma, saliva, urine, cerebrospinal fl uid and postmortem brain tissue 73 – 75 , although these are in fl uenced by circadian rhythms, daily activities and even sleep patterns 76 .”
Chang, C., Hsu, J.-Y., Hsiao, P.-Z., Chen, Y.-C., & Liao, P. (2023) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.2c00294 · Cited by 7 · see citing works
A Metabolomic Approach for Predicting Diurnal Changes in Cortisol
Eshima, J., Davis, T. J., Bean, H. D., Fricks, J., & Smith, B. S. (2020) · Metabolites · doi:10.3390/metabo10050194 · Cited by 7 · see citing works
“The human urinary metabolome has been previously characterized in many different studies, yet few have considered the significant effects of temporal changes [23,24,26,45].”
BackgroundEpigenetics of Sleep Disruption
Gazerani, P. (2020) · OBM Neurobiology · doi:10.21926/obm.neurobiol.2003071 · Cited by 6 · see citing works
Chang, C., Hsu, J.-Y., Lo, Y., Liu, Y., Mee-inta, O., Lee, H., Kuo, Y., & Liao, P. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00587 · Cited by 6 · see citing works
Dulong, S., Huang, Q., Innominato, P. F., Karaboué, A., Bouchahda, M., Pruvost, A., Théodoro, F., Agrofoglio, L. A., Adam, R. A., Finkenstädt, B., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-03247-2 · Cited by 6 · see citing works
Circadian Lipidomics: Analysis of Lipid Metabolites Around the Clock
Loizides‐Mangold, U., Petrenko, V., & Dibner, C. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0381-9_13 · Cited by 6 · see citing works
Athersuch, T. J. (2018) · Springer eBooks · doi:10.1007/978-3-319-89321-1_6 · Cited by 6 · see citing works
Fiorin, F. D. S., Godinho, D. B., dos Santos, E. B., Aguiar, A. S., Schuch, F. B., de Mello, M. T., Radak, Z. O., Fighera, M. R., & Royes, L. F. F. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115156 · Cited by 6 · see citing works
An improved approach to report creatinine-corrected analyte concentrations in urine
Jain, R. B. (2016) · Sustainable Environment · doi:10.1080/23311843.2016.1259880 · Cited by 5 · see citing works
Chen, T., Jia, J., Gao, C., Zhong, Q., Tang, L., Sui, X., Li, S., Chen, C., & Zhang, Z. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111397 · Cited by 4 · see citing works
“Synapse play a critical role in the maintenance of memory, and the damage of synaptic plasticity after sleep deprivation is a key factor in memory impairment(Giri et al., 2021; Gisabella et al., 2019).”
- Authors
- Giskeødegård, G. F., Davies, S. K., Revell, V. L., Keun, H., & Skene, D. J.
- Affiliations
- Norwegian University of Science and Technology (NO)
- University of Surrey (GB)
- Imperial College London (GB)
- Corresponding author
- Skene, Debra J.
- Venue
- Scientific Reports
- Published
- 2015-10-09
- Volume
- 5
- Issue
- 1
- Pages
- 14843-14843
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4598809
- OpenAlex
- W2283245187
- Cited by
- 135
- References
- 43
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 7 · 2023: 13 · 2022: 12 · 2021: 10 · 2020: 18 · 2019: 13 · 2018: 20 · 2017: 16 · 2016: 9 · 2015: 1
- FWCI
- 6.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- University of Surrey
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council (BB/I019405/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- diurnal cycle, urinary metabolome, sleep deprivation, total sleep deprivation, diurnal variation, urinary biomarkers, 1H NMR, metabolite profiles, sleep and metabolism, indoxyl sulfate, trimethylamine N-oxide, taurine, dimethylamine
- MeSH terms
- Adolescent, Adult, Circadian Rhythm, Citrates, Creatinine, Dimethylamines, Formates, Humans, Male, Magnetic Resonance Spectroscopy, Sleep, Sleep Deprivation, Taurine, Time Factors, Multivariate Analysis, Principal Component Analysis, Metabolomics, Metabolome, Young Adult
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