{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:54:42Z","timestamp":1787064882984,"version":"build-2736575974"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19 AI109755"],"award-info":[{"award-number":["U19 AI109755"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI152161"],"award-info":[{"award-number":["R01 AI152161"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K23 AI144040"],"award-info":[{"award-number":["K23 AI144040"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR002378"],"award-info":[{"award-number":["UL1 TR002378"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-32679-3","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T16:54:46Z","timestamp":1769187286000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multicohort assessment of plasma metabolic signatures of tuberculosis disease in children: a retrospective cross-sectional study"],"prefix":"10.1038","volume":"16","author":[{"given":"Mary M.","family":"Nellis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juaneta","family":"Luiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devan","family":"Jaganath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaynab","family":"Mousavian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esin","family":"Nkereuwem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Wambi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Calderon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandar","family":"Paradkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutuja","family":"Nerurkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly F.","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarti","family":"Kinikar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Wobudeya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather J.","family":"Zar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean P.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Segal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Sigal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle L.","family":"Swaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adithya","family":"Cattamanchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel D.","family":"Ernst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Kampmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"COMBO Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Baard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yekiwe","family":"Hlombe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Workman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaretha","family":"Prins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdoulie","family":"Tunkara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binta","family":"Saidy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis S.","family":"Mendy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madikoi","family":"Danso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie P.","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Boakarie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarjo","family":"Koita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheriff","family":"Kandeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jascent","family":"Nakafero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertrude","family":"Nanyonga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliet","family":"Namboowa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Nabakka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nsereko","family":"Moses","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainebyona","family":"Aggrey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Andama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moorine","family":"Sekadde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Mudiope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezekiel","family":"Mupere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hellen Aanyu","family":"Tukamuhebwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amita","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidya","family":"Mave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"32679_CR1","volume-title":"Global Tuberculosis Report 2024","author":"WHO","year":"2024","unstructured":"WHO. Global Tuberculosis Report 2024 (World Health Organization, 2024)."},{"issue":"9","key":"32679_CR2","doi-asserted-by":"publisher","first-page":"e898","DOI":"10.1016\/S2214-109X(17)30289-9","volume":"5","author":"PJ Dodd","year":"2017","unstructured":"Dodd, P. J., Yuen, C. M., Sismanidis, C., Seddon, J. A. & Jenkins, H. E. The global burden of tuberculosis mortality in children: a mathematical modelling study. Lancet Glob. Health. 5(9), e898\u2013e906 (2017).","journal-title":"Lancet Glob. Health."},{"issue":"2","key":"32679_CR3","doi-asserted-by":"publisher","first-page":"e207","DOI":"10.1016\/S2214-109X(21)00462-9","volume":"10","author":"S Yerramsetti","year":"2022","unstructured":"Yerramsetti, S., Cohen, T., Atun, R. & Menzies, N. A. Global estimates of paediatric tuberculosis incidence in 2013\u201319: a mathematical modelling analysis. Lancet Glob. Health. 10(2), e207\u2013e215 (2022).","journal-title":"Lancet Glob. Health."},{"issue":"9454","key":"32679_CR4","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/S0140-6736(05)17702-2","volume":"365","author":"HJ Zar","year":"2005","unstructured":"Zar, H. J., Hanslo, D., Apolles, P., Swingler, G. & Hussey, G. Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: a prospective study. Lancet 365(9454), 130\u2013134 (2005).","journal-title":"Lancet"},{"issue":"11","key":"32679_CR5","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/S1473-3099(11)70167-0","volume":"11","author":"MP Nicol","year":"2011","unstructured":"Nicol, M. P. et al. Accuracy of the Xpert MTB\/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study. Lancet. Infect Dis. 11(11), 819\u2013824 (2011).","journal-title":"Lancet. Infect Dis."},{"issue":"10","key":"32679_CR6","doi-asserted-by":"publisher","first-page":"e261","DOI":"10.1097\/INF.0000000000001960","volume":"37","author":"MP Nicol","year":"2018","unstructured":"Nicol, M. P. et al. Accuracy of Xpert Mtb\/Rif Ultra for the Diagnosis of Pulmonary Tuberculosis in Children. Pediatr. Infect. Dis. J. 37(10), e261\u2013e263 (2018).","journal-title":"Pediatr. Infect. Dis. J."},{"issue":"12","key":"32679_CR7","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1164\/rccm.201904-0772OC","volume":"200","author":"HJ Zar","year":"2019","unstructured":"Zar, H. J. et al. Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens. Am. J. Resp. Crit. Care Med. 200(12), 1531\u20131538 (2019).","journal-title":"Am. J. Resp. Crit. Care Med."},{"key":"32679_CR8","doi-asserted-by":"crossref","unstructured":"Kay AW, Ness T, Verkuijl SE, et al. Xpert MTB\/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children. Cochrane Database Syst. Rev. (2022).","DOI":"10.1002\/14651858.CD013359.pub3"},{"issue":"1","key":"32679_CR9","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1016\/S2214-109X(23)00469-2","volume":"12","author":"EC Church","year":"2024","unstructured":"Church, E. C. et al. Oral swabs with a rapid molecular diagnostic test for pulmonary tuberculosis in adults and children: a systematic review. Lancet Glob. Health. 12(1), e45\u2013e54 (2024).","journal-title":"Lancet Glob. Health."},{"key":"32679_CR10","volume-title":"High-priority target product profiles for new tuberculosis diagnostics: Report of a consensus meeting","author":"WHO","year":"2014","unstructured":"WHO. High-priority target product profiles for new tuberculosis diagnostics: Report of a consensus meeting (World Health Organization, 2014)."},{"key":"32679_CR11","volume-title":"Target product profiles for tuberculosis diagnosis and detection of drug resistance","author":"WHO","year":"2024","unstructured":"WHO. Target product profiles for tuberculosis diagnosis and detection of drug resistance (World Health Organization, 2024)."},{"issue":"220 Suppl 3","key":"32679_CR12","doi-asserted-by":"publisher","first-page":"S108","DOI":"10.1093\/infdis\/jiz356","volume":"220","author":"PK Drain","year":"2019","unstructured":"Drain, P. K. et al. Guidance for Studies Evaluating the Accuracy of Biomarker-Based Nonsputum Tests to Diagnose Tuberculosis. J. Infect Dis. 220(220 Suppl 3), S108-s115 (2019).","journal-title":"J. Infect Dis."},{"issue":"10","key":"32679_CR13","doi-asserted-by":"publisher","first-page":"e0205398","DOI":"10.1371\/journal.pone.0205398","volume":"13","author":"JM Collins","year":"2018","unstructured":"Collins, J. M. et al. High-resolution plasma metabolomics analysis to detect Mycobacterium tuberculosis-associated metabolites that distinguish active pulmonary tuberculosis in humans. PLoS ONE 13(10), e0205398 (2018).","journal-title":"PLoS ONE"},{"issue":"1","key":"32679_CR14","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1513\/AnnalsATS.201510-676LE","volume":"13","author":"JM Collins","year":"2016","unstructured":"Collins, J. M., Kempker, R. R., Ziegler, T. R., Blumberg, H. M. & Jones, D. P. Metabolomics and Mycobacterial Disease: Don\u2019t Forget the Bioinformatics. Ann. Am. Thorac. Soc. 13(1), 141\u2013142 (2016).","journal-title":"Ann. Am. Thorac. Soc."},{"issue":"12","key":"32679_CR15","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1021\/acs.chemrestox.6b00179","volume":"29","author":"K Uppal","year":"2016","unstructured":"Uppal, K. et al. Computational Metabolomics: A Framework for the Million Metabolome. Chem. Res. Toxicol. 29(12), 1956\u20131975 (2016).","journal-title":"Chem. Res. Toxicol."},{"key":"32679_CR16","doi-asserted-by":"crossref","unstructured":"Collins JM, Siddiqa A, Jones DP, et al. Tryptophan catabolism reflects disease activity in human tuberculosis. JCI Insight. (2020).","DOI":"10.1172\/jci.insight.137131"},{"issue":"8","key":"32679_CR17","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1093\/cid\/cix550","volume":"65","author":"CG Adu-Gyamfi","year":"2017","unstructured":"Adu-Gyamfi, C. G. et al. Plasma Indoleamine 2, 3-Dioxygenase, a Biomarker for Tuberculosis in Human Immunodeficiency Virus-Infected Patients. Clin. Infect. Dis. 65(8), 1356\u20131358 (2017).","journal-title":"Clin. Infect. Dis."},{"issue":"6","key":"32679_CR18","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1093\/cid\/ciab232","volume":"73","author":"C Adu-Gyamfi","year":"2021","unstructured":"Adu-Gyamfi, C. et al. Plasma Kynurenine-to-Tryptophan Ratio, a Highly Sensitive Blood-Based Diagnostic Tool for Tuberculosis in Pregnant Women Living With Human Immunodeficiency Virus (HIV). Clin. Infect. Dis. 73(6), 1027\u20131036 (2021).","journal-title":"Clin. Infect. Dis."},{"key":"32679_CR19","unstructured":"Collins JM, Bobosha K, Narayanan N, et al. A plasma metabolic signature to diagnose pulmonary tuberculosis and monitor treatment response. J. Infect. Dis. (2025)."},{"key":"32679_CR20","doi-asserted-by":"publisher","first-page":"774043","DOI":"10.3389\/fimmu.2021.774043","volume":"12","author":"JA Tornheim","year":"2021","unstructured":"Tornheim, J. A. et al. The Kynurenine\/Tryptophan Ratio Is a Sensitive Biomarker for the Diagnosis of Pediatric Tuberculosis Among Indian Children. Front. Immunol. 12, 774043 (2021).","journal-title":"Front. Immunol."},{"issue":"1","key":"32679_CR21","doi-asserted-by":"publisher","first-page":"19527","DOI":"10.1038\/s41598-020-75513-8","volume":"10","author":"NK Dutta","year":"2020","unstructured":"Dutta, N. K. et al. Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children. Sci. Rep. 10(1), 19527 (2020).","journal-title":"Sci. Rep."},{"key":"32679_CR22","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.3389\/fimmu.2017.01059","volume":"8","author":"A Dreesman","year":"2017","unstructured":"Dreesman, A. et al. Age-Stratified T Cell Responses in Children Infected with Mycobacterium tuberculosis. Front Immunol. 8, 1059 (2017).","journal-title":"Front Immunol."},{"issue":"1","key":"32679_CR23","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.cmet.2023.12.009","volume":"36","author":"ZA Bacigalupa","year":"2024","unstructured":"Bacigalupa, Z. A., Landis, M. D. & Rathmell, J. C. Nutrient inputs and social metabolic control of T cell fate. Cell Metab. 36(1), 10\u201320 (2024).","journal-title":"Cell Metab."},{"key":"32679_CR24","doi-asserted-by":"crossref","unstructured":"Graham SM, Cuevas LE, Jean-Philippe P, et al. Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children: An Update. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. (2015).","DOI":"10.1093\/cid\/civ581"},{"issue":"9","key":"32679_CR25","doi-asserted-by":"publisher","first-page":"e1009941","DOI":"10.1371\/journal.ppat.1009941","volume":"17","author":"JM Collins","year":"2021","unstructured":"Collins, J. M. et al. TCA cycle remodeling drives proinflammatory signaling in humans with pulmonary tuberculosis. PLoS Pathog. 17(9), e1009941 (2021).","journal-title":"PLoS Pathog."},{"issue":"1 Suppl","key":"32679_CR26","doi-asserted-by":"publisher","first-page":"S132","DOI":"10.1007\/s11306-011-0332-1","volume":"9","author":"QA Soltow","year":"2013","unstructured":"Soltow, Q. A. et al. High-performance metabolic profiling with dual chromatography-Fourier-transform mass spectrometry (DC-FTMS) for study of the exposome. Metabolomics 9(1 Suppl), S132-143 (2013).","journal-title":"Metabolomics"},{"issue":"2","key":"32679_CR27","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1093\/toxsci\/kfv198","volume":"148","author":"YM Go","year":"2015","unstructured":"Go, Y. M. et al. Reference Standardization for Mass Spectrometry and High-Resolution Metabolomics Applications to Exposome Research. Toxicol. Sci. 148(2), 531\u2013542 (2015).","journal-title":"Toxicol. Sci."},{"issue":"15","key":"32679_CR28","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1093\/bioinformatics\/btp291","volume":"25","author":"T Yu","year":"2009","unstructured":"Yu, T., Park, Y., Johnson, J. M. & Jones, D. P. apLCMS\u2013adaptive processing of high-resolution LC\/MS data. Bioinformatics 25(15), 1930\u20131936 (2009).","journal-title":"Bioinformatics"},{"key":"32679_CR29","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1471-2105-14-15","volume":"14","author":"K Uppal","year":"2013","unstructured":"Uppal, K. et al. xMSanalyzer: automated pipeline for improved feature detection and downstream analysis of large-scale, non-targeted metabolomics data. BMC Bioinform. 14, 15 (2013).","journal-title":"BMC Bioinform."},{"issue":"13","key":"32679_CR30","doi-asserted-by":"publisher","first-page":"8836","DOI":"10.1021\/acs.analchem.0c00338","volume":"92","author":"KH Liu","year":"2020","unstructured":"Liu, K. H. et al. Reference Standardization for Quantification and Harmonization of Large-Scale Metabolomics. Anal Chem. 92(13), 8836\u20138844 (2020).","journal-title":"Anal Chem."},{"issue":"7","key":"32679_CR31","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucl. Acids Res. 43(7), e47 (2015).","journal-title":"Nucl. Acids Res."},{"issue":"7","key":"32679_CR32","doi-asserted-by":"publisher","first-page":"e1003123","DOI":"10.1371\/journal.pcbi.1003123","volume":"9","author":"S Li","year":"2013","unstructured":"Li, S. et al. Predicting network activity from high throughput metabolomics. PLoS Comput. Biol. 9(7), e1003123 (2013).","journal-title":"PLoS Comput. Biol."},{"issue":"5","key":"32679_CR33","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.cell.2017.04.026","volume":"169","author":"S Li","year":"2017","unstructured":"Li, S. et al. Metabolic Phenotypes of Response to Vaccination in Humans. Cell 169(5), 862-877.e817 (2017).","journal-title":"Cell"},{"issue":"7","key":"32679_CR34","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1002\/sim.4780090710","volume":"9","author":"Y Hochberg","year":"1990","unstructured":"Hochberg, Y. & Benjamini, Y. More powerful procedures for multiple significance testing. Stat. Med. 9(7), 811\u2013818 (1990).","journal-title":"Stat. Med."},{"key":"32679_CR35","unstructured":"Ishwaran H, Kogalur U. Fast Unified Random Forests for Survival, Regression, and Classification (RF-SRC). (2025)."},{"issue":"5","key":"32679_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v028.i05","volume":"28","author":"M Kuhn","year":"2008","unstructured":"Kuhn, M. Building Predictive Models in R Using the caret Package. J. Stat. Softw. 28(5), 1\u201326 (2008).","journal-title":"J. Stat. Softw."},{"issue":"220 Suppl 3","key":"32679_CR37","doi-asserted-by":"publisher","first-page":"S91","DOI":"10.1093\/infdis\/jiz097","volume":"220","author":"CM Denkinger","year":"2019","unstructured":"Denkinger, C. M. et al. Guidance for the Evaluation of Tuberculosis Diagnostics That Meet the World Health Organization (WHO) Target Product Profiles: An Introduction to WHO Process and Study Design Principles. J. Infect. Dis. 220(220 Suppl 3), S91-s98 (2019).","journal-title":"J. Infect. Dis."},{"issue":"3","key":"32679_CR38","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1093\/cid\/ciad270","volume":"77","author":"S Suliman","year":"2023","unstructured":"Suliman, S., Jaganath, D. & DiNardo, A. Predicting Pediatric Tuberculosis: The Need for Age-Specific Host Biosignatures. Clin. Infect. Dis. 77(3), 450\u2013452 (2023).","journal-title":"Clin. Infect. Dis."},{"issue":"4","key":"32679_CR39","doi-asserted-by":"publisher","first-page":"e0004026","DOI":"10.1371\/journal.pgph.0004026","volume":"5","author":"PJ Kitonsa","year":"2025","unstructured":"Kitonsa, P. J. et al. The Accuracy of the Uganda National Tuberculosis and Leprosy Program diagnostic algorithm and the World Health Organisation treatment decision algorithms for childhood tuberculosis: A retrospective analysis. PLOS Glob Public Health 5(4), e0004026 (2025).","journal-title":"PLOS Glob Public Health"},{"key":"32679_CR40","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.ijid.2020.08.028","volume":"99","author":"CG Adu-Gyamfi","year":"2020","unstructured":"Adu-Gyamfi, C. G. et al. Diagnostic accuracy of plasma kynurenine\/tryptophan ratio, measured by enzyme-linked immunosorbent assay, for pulmonary tuberculosis. Int. J. Infect. Dis. 99, 441\u2013448 (2020).","journal-title":"Int. J. Infect. Dis."},{"issue":"7","key":"32679_CR41","doi-asserted-by":"publisher","first-page":"e40221","DOI":"10.1371\/journal.pone.0040221","volume":"7","author":"J Weiner 3rd","year":"2012","unstructured":"Weiner, J. 3rd. et al. Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients. PLoS ONE 7(7), e40221 (2012).","journal-title":"PLoS ONE"},{"key":"32679_CR42","doi-asserted-by":"crossref","unstructured":"Khadka M, Todor A, Maner-Smith KM, et al. The Effect of Anticoagulants, Temperature, and Time on the Human Plasma Metabolome and Lipidome from Healthy Donors as Determined by Liquid Chromatography-Mass Spectrometry. Biomolecules. (2019)","DOI":"10.3390\/biom9050200"},{"issue":"3","key":"32679_CR43","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1128\/CVI.05402-11","volume":"19","author":"Y Suzuki","year":"2012","unstructured":"Suzuki, Y. et al. Serum indoleamine 2,3-dioxygenase activity predicts prognosis of pulmonary tuberculosis. Clin. Vaccine Immunol. 19(3), 436\u2013442 (2012).","journal-title":"Clin. Vaccine Immunol."},{"issue":"2","key":"32679_CR44","doi-asserted-by":"publisher","first-page":"e0149823","DOI":"10.1371\/journal.pone.0149823","volume":"11","author":"CY Chiu","year":"2016","unstructured":"Chiu, C. Y. et al. Metabolomics Reveals Dynamic Metabolic Changes Associated with Age in Early Childhood. PLoS ONE 11(2), e0149823 (2016).","journal-title":"PLoS ONE"},{"key":"32679_CR45","doi-asserted-by":"crossref","unstructured":"Schiff HF, Walker NF, Ugarte-Gil C, et al. Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers. JCI Insight. (2024).","DOI":"10.1172\/jci.insight.173273"},{"key":"32679_CR46","doi-asserted-by":"crossref","unstructured":"Worodria W, Castro R, Kik SV, et al. An independent, multi-country head-to-head accuracy comparison of automated chest x-ray algorithms for the triage of pulmonary tuberculosis. medRxiv. (2024).","DOI":"10.1101\/2024.06.19.24309061"},{"issue":"6","key":"32679_CR47","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1016\/j.immuni.2009.10.007","volume":"31","author":"L Desvignes","year":"2009","unstructured":"Desvignes, L. & Ernst, J. D. Interferon-gamma-responsive nonhematopoietic cells regulate the immune response to Mycobacterium tuberculosis. Immunity 31(6), 974\u2013985 (2009).","journal-title":"Immunity"},{"issue":"1","key":"32679_CR48","doi-asserted-by":"publisher","first-page":"E62","DOI":"10.1073\/pnas.1711373114","volume":"115","author":"US Gautam","year":"2018","unstructured":"Gautam, U. S. et al. In vivo inhibition of tryptophan catabolism reorganizes the tuberculoma and augments immune-mediated control of Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U S A. 115(1), E62-e71 (2018).","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"issue":"2","key":"32679_CR49","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/s41590-021-01121-x","volume":"23","author":"EF McCaffrey","year":"2022","unstructured":"McCaffrey, E. F. et al. The immunoregulatory landscape of human tuberculosis granulomas. Nat. Immunol. 23(2), 318\u2013329 (2022).","journal-title":"Nat. Immunol."},{"issue":"8","key":"32679_CR50","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1016\/j.cmet.2023.06.004","volume":"35","author":"C Xue","year":"2023","unstructured":"Xue, C. et al. Tryptophan metabolism in health and disease. Cell Metab. 35(8), 1304\u20131326 (2023).","journal-title":"Cell Metab."},{"issue":"10402","key":"32679_CR51","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/S0140-6736(23)01231-X","volume":"402","author":"A Bhargava","year":"2023","unstructured":"Bhargava, A. et al. Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India (RATIONS): a field-based, open-label, cluster-randomised, controlled trial. Lancet 402(10402), 627\u2013640 (2023).","journal-title":"Lancet"},{"key":"32679_CR52","doi-asserted-by":"crossref","unstructured":"Franco JV, Bongaerts B, Metzendorf MI, et al. Undernutrition as a risk factor for tuberculosis disease. Cochrane Database Syst. Rev. (2024).","DOI":"10.1002\/14651858.CD015890.pub2"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32679-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32679-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32679-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T01:03:20Z","timestamp":1769475800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32679-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["32679"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-32679-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7086994\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]},"assertion":[{"value":"9 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3283"}}