{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T21:40:43Z","timestamp":1776289243825,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Infectious Disease Reports"],"abstract":"<jats:p>Background: Torque Teno Virus (TTV) viremia has been proposed as a marker for infection risk in kidney transplant (KT) recipients. This study aimed to evaluate the prognostic value of TTV levels for predicting infections post-KT. Methods: A cohort of 82 KT patients was analyzed. TTV loads were measured before KT and at the time of cutoff analysis (mean time since KT: 20.2 \u00b1 10.3 months). Infections were tracked within six months following the time of cutoff analysis. Univariable analyses and a supervised machine learning approach (logistic regression with leave-one-out cross-validation) were conducted to rigorously assess TTV\u2019s predictive ability for post-transplant infection. Results: Seventy-two patients (87.8%) had detectable TTV before KT. Of these, 30.5% developed infections, predominantly viral. TTV loads increased significantly from 3.35 \u00b1 1.67 log10 cp\/mL before KT to 4.53 \u00b1 1.93 log10 cp\/mL at the time of cutoff analysis. Infected patients had significantly higher TTV loads (5.39 \u00b1 1.68 log10 vs. 4.16 \u00b1 1.94 log10 cp\/mL, p = 0.0057). The optimal TTV threshold for predicting infection at the time of cutoff analysis was 5.16 log10 cp\/mL, with 60% sensitivity and 81% specificity. Machine learning models improved performance, with sensitivity and specificity 0.805 and 0.735, respectively. Conclusions: TTV viremia may serve as a biomarker for infection risk, particularly when used with other clinical variables. The identified TTV threshold of 5.16 log10 cp\/mL offers a practical tool for clinical decision-making, particularly when integrated with a machine learning model. Further studies with larger cohorts are needed to validate these findings and refine clinical applications.<\/jats:p>","DOI":"10.3390\/idr17050107","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Torque Teno Virus as a Biomarker for Infection Risk in Kidney Transplant Recipients: A Machine Learning-Enabled Cohort Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2325-1817","authenticated-orcid":false,"given":"Sara","family":"Querido","sequence":"first","affiliation":[{"name":"Renal Transplantation Unit, Nephrology Department, Hospital de Santa Cruz, Unidade Local de Sa\u00fade de Lisboa Ocidental, 2790-134 Carnaxide, Portugal"},{"name":"CHRC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8911-3380","authenticated-orcid":false,"given":"Lu\u00eds","family":"Ramalhete","sequence":"additional","affiliation":[{"name":"IPST\u2014Instituto Portugu\u00eas do Sangue e da Transplanta\u00e7\u00e3o, Alameda das Linhas de Torres 117, 1769-001 Lisboa, Portugal"},{"name":"NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"iNOVA4Health\u2014Advancing Precision Medicine, N\u00facleo de Investiga\u00e7\u00e3o em Doen\u00e7as Renais, NMS\u2014NOVA Medical School, FCM\u2014Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3271-8255","authenticated-orcid":false,"given":"Perp\u00e9tua","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Microbiology and Molecular Biology, Department of Clinical Pathology, Unidade Local de Sa\u00fade de Lisboa Ocidental, 1349-019 Lisboa, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar Egas Moniz (CiiEM), IUEM, 2829-511 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9674-8862","authenticated-orcid":false,"given":"Andr\u00e9","family":"Weigert","sequence":"additional","affiliation":[{"name":"Renal Transplantation Unit, Nephrology Department, Hospital de Santa Cruz, Unidade Local de Sa\u00fade de Lisboa Ocidental, 2790-134 Carnaxide, Portugal"},{"name":"Pharmacology and Neurosciences Institute, Faculdade de Medicina, Universidade de Lisboa, 1649-004 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1056\/NEJMra064928","article-title":"Infection in solid-organ transplant recipients","volume":"357","author":"Fishman","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1080\/17425255.2017.1395413","article-title":"Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients","volume":"13","author":"Andrews","year":"2017","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/(SICI)1099-1654(199904\/06)9:2<73::AID-RMV254>3.0.CO;2-5","article-title":"Time to consider the concept of a commensal virus?","volume":"9","author":"Griffiths","year":"1999","journal-title":"Rev. Med. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2393","DOI":"10.1002\/rmv.2393","article-title":"Torque teno virus load as marker of rejection and infection in solid organ transplantation: A systematic review and meta-analysis","volume":"33","author":"Roos","year":"2023","journal-title":"Rev. Med. Virol."},{"key":"ref_5","first-page":"589","article-title":"Torquetenovirus: The human virome from bench to bedside","volume":"22","author":"Focosi","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13336","DOI":"10.1073\/pnas.1517494112","article-title":"Noninvasive monitoring of infection and rejection after lung transplantation","volume":"112","author":"Martin","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e13778","DOI":"10.1111\/tid.13778","article-title":"Viruses, friends, and foes: The case of Torque Teno Virus and the net state of immunosuppression","volume":"24","author":"Redondo","year":"2022","journal-title":"Transpl. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.trre.2019.03.004","article-title":"Torque-Teno virus viral load as a potential endogenous marker of immune function in solid organ transplantation","volume":"33","author":"Rezahosseini","year":"2019","journal-title":"Transpl. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1681\/ASN.2017050477","article-title":"The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical Correlations","volume":"29","author":"Nickeleit","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e13528","DOI":"10.1111\/ctr.13528","article-title":"BK polyomavirus in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice","volume":"33","author":"Hirsch","year":"2019","journal-title":"Clin. Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1111\/ajt.15898","article-title":"The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection","volume":"20","author":"Loupy","year":"2020","journal-title":"Am. J. Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gore, E.J., Gomes-Neto, A.W., Wang, L., Bakker, S.J.L., Niesters, H.G.M., de Joode, A.A.E., Verschuuren, E.A.M., Westra, J., and Van Leer-Buter, C. (2020). Torquetenovirus Serum Load and Long-Term Outcomes in Renal Transplant Recipients. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020440"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jinf.2019.05.010","article-title":"Torquetenovirus viremia for early prediction of graft rejection after kidney transplantation","volume":"79","author":"Solis","year":"2019","journal-title":"J. Infect."},{"key":"ref_15","first-page":"809","article-title":"Receiver-operating characteristic (ROC) plots: A fundamental evaluation tool in clinical medicine","volume":"12","author":"Zweig","year":"1993","journal-title":"Stat. Med."},{"key":"ref_16","first-page":"2349","article-title":"Orange: Data mining toolbox in Python","volume":"14","author":"Curk","year":"2013","journal-title":"J. Mach. Learn. Res."},{"key":"ref_17","unstructured":"Yang, X.-S., Sanjeevi, C.B., and Rangachari, R. (2020, January 8\u201310). Visualizing data using t-SNE. Proceedings of the International Conference on Artificial Intelligence and Computer Vision (AICV 2020), Cairo, Egypt."},{"key":"ref_18","unstructured":"Chen, L., Zhang, Y., and Wang, S. (2021). Logistic regression in machine learning. Symmetry, 13."},{"key":"ref_19","first-page":"625","article-title":"Leave-one-out cross-validation","volume":"13","author":"Huang","year":"2020","journal-title":"Stat. Anal. Data Min."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jmp.2018.03.001","article-title":"A tutorial on Gaussian process regression: Modelling, exploring, and exploiting functions","volume":"85","author":"Schulz","year":"2018","journal-title":"J. Math. Psychol."},{"key":"ref_21","first-page":"1289","article-title":"An extensive empirical study of feature selection metrics for text classification","volume":"3","author":"Forman","year":"2003","journal-title":"J. Mach. Learn. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1016\/j.cmi.2020.01.011","article-title":"Assessment of prevalence and load of torquetenovirus viraemia in a large cohort of healthy blood donors","volume":"26","author":"Focosi","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.exger.2018.09.003","article-title":"Torquetenovirus (TTV) load is associated with mortality in Italian elderly subjects","volume":"112","author":"Giacconi","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Querido, S., Martins, C., Gomes, P., Pessanha, M.A., Arroz, M.J., Adrag\u00e3o, T., Casqueiro, A., Oliveira, R., Costa, I., and Azinheira, J. (2023). Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort Study. Viruses, 15.","DOI":"10.3390\/v15071464"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104871","DOI":"10.1016\/j.jcv.2021.104871","article-title":"Torque teno virus loads after kidney transplantation predict allograft rejection but not viral infection","volume":"140","author":"Wunderink","year":"2021","journal-title":"J. Clin. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s13063-023-07216-0","article-title":"A multicentre, patient- and assessor-blinded, non-inferiority, randomised and controlled phase II trial to compare standard and torque teno virus-guided immunosuppression in kidney transplant recipients in the first year after transplantation: TTVguideIT","volume":"24","author":"Haupenthal","year":"2023","journal-title":"Trials"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1099\/vir.0.070094-0","article-title":"Short-term kinetics of torque teno virus viraemia after induction immunosuppression confirm T lymphocytes as the main replication-competent cells","volume":"96","author":"Focosi","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_28","first-page":"404","article-title":"Torque Teno Virus for the monitoring of infection risk in kidney transplant patients: First clinical application","volume":"17","author":"Schiemann","year":"2017","journal-title":"Am. J. Transplant."},{"key":"ref_29","first-page":"782","article-title":"Co-infections and their impact on Torque Teno Virus replication","volume":"91","author":"Maggi","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jcv.2019.03.018","article-title":"No correlation between Torque Teno virus viral load and BK virus replication after kidney transplantation","volume":"116","author":"Handala","year":"2019","journal-title":"J. Clin. Virol."}],"container-title":["Infectious Disease Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2036-7449\/17\/5\/107\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:38:16Z","timestamp":1760035096000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2036-7449\/17\/5\/107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["idr17050107"],"URL":"https:\/\/doi.org\/10.3390\/idr17050107","relation":{},"ISSN":["2036-7449"],"issn-type":[{"value":"2036-7449","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,2]]}}}