{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:27:00Z","timestamp":1791300420423,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genomics"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Thiopurine medications are widely used for the treatment of acute lymphoblastic leukemia and inflammatory bowel disease. However, thiopurine-induced hemotoxicity occurs in up to 30% of patients, which causes substantial morbidity and limits therapeutic success. These adverse effects are associated with genetic variation in\n                    <jats:italic>TPMT<\/jats:italic>\n                    and\n                    <jats:italic>NUDT15<\/jats:italic>\n                    , which encode key enzymes involved in thiopurine metabolism. While the global distribution of\n                    <jats:italic>TPMT<\/jats:italic>\n                    variability has been extensively studied, less is known about the ethnogeographic variability of\n                    <jats:italic>NUDT15,<\/jats:italic>\n                    and no meta-analysis of available population frequencies has been reported. In this study, we aggregated genetic data from 150 studies and repositories comprising genotypes from a total of 1,401,592 individuals across 55 countries. We further synthesize the available clinical evidence for functional effects of\n                    <jats:italic>NUDT15*5<\/jats:italic>\n                    and\n                    <jats:italic>NUDT15*6<\/jats:italic>\n                    , which are currently considered as variants with indeterminate functional effects. This synthesis indicates that both alleles significantly increase thiopurine adverse event risk. We aggregate the genetic information to spectra of functional variability to generate the first global maps of NUDT15 metabolizer phenotypes. We observe a graded distribution of NUDT15 deficiency, peaking in East Asia (46% of all individuals exhibit reduced NUDT15 activity) and declining across Central Asia (13.6%), Middle Eastern populations (3.8%) and Europe (2.1%). NUDT15 deficiency is furthermore prevalent on the Western coast of South and Central America but absent in Africa. Overall, our results provide a valuable resource for population-specific\n                    <jats:italic>NUDT15<\/jats:italic>\n                    allele and metabolizer phenotype distributions, which can guide thiopurine risk assessment on a global scale.\n                  <\/jats:p>","DOI":"10.1186\/s40246-026-00959-2","type":"journal-article","created":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T16:28:19Z","timestamp":1775320099000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comprehensive overview of the global pharmacogenetic and functional variability in NUDT15"],"prefix":"10.1186","volume":"20","author":[{"given":"Yitian","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas M.","family":"Lauschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker M.","family":"Lauschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,4]]},"reference":[{"key":"959_CR1","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1093\/hmg\/8.2.367","volume":"8","author":"MM Ameyaw","year":"1999","unstructured":"Ameyaw MM, Collie-Duguid ES, Powrie RH, Ofori-Adjei D, McLeod HL. Thiopurine methyltransferase alleles in British and Ghanaian populations. Hum Mol Genet. 1999;8:367\u201370. https:\/\/doi.org\/10.1093\/hmg\/8.2.367.","journal-title":"Hum Mol Genet"},{"key":"959_CR2","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526:68\u201374. https:\/\/doi.org\/10.1038\/nature15393.","journal-title":"Nature"},{"key":"959_CR3","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.2169\/internalmedicine.47.1268","volume":"47","author":"H Ban","year":"2008","unstructured":"Ban H, Andoh A, Tanaka A, Tsujikawa T, Sasaki M, Saito Y, et al. Analysis of thiopurine S-methyltransferase genotypes in Japanese patients with inflammatory bowel disease. Intern Med. 2008;47:1645\u20138. https:\/\/doi.org\/10.2169\/internalmedicine.47.1268.","journal-title":"Intern Med"},{"key":"959_CR4","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1097\/mib.0000000000001148","volume":"23","author":"K Chao","year":"2017","unstructured":"Chao K, Wang X, Cao Q, Qian J, Wu K, Zhu X, et al. Combined detection of NUDT15 variants could highly predict thiopurine-induced leukopenia in Chinese patients with inflammatory bowel disease: a multicenter analysis. Inflamm Bowel Dis. 2017;23:1592\u20139. https:\/\/doi.org\/10.1097\/mib.0000000000001148.","journal-title":"Inflamm Bowel Dis"},{"key":"959_CR5","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1097\/MIB.0b013e318281f28f","volume":"19","author":"M Chaparro","year":"2013","unstructured":"Chaparro M, Ord\u00e1s I, Cabr\u00e9 E, Garcia-Sanchez V, Bastida G, Pe\u00f1alva M, et al. Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients. Inflamm Bowel Dis. 2013;19:1404\u201310. https:\/\/doi.org\/10.1097\/MIB.0b013e318281f28f.","journal-title":"Inflamm Bowel Dis"},{"key":"959_CR6","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41586-023-06045-0","volume":"625","author":"S Chen","year":"2024","unstructured":"Chen S, Francioli LC, Goodrich JK, Collins RL, Kanai M, Wang Q, et al. A genomic mutational constraint map using variation in 76,156 human genomes. Nature. 2024;625:92\u2013100. https:\/\/doi.org\/10.1038\/s41586-023-06045-0.","journal-title":"Nature"},{"key":"959_CR7","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1097\/00008571-199902000-00006","volume":"9","author":"ES Collie-Duguid","year":"1999","unstructured":"Collie-Duguid ES, Pritchard SC, Powrie RH, Sludden J, Collier DA, Li T, et al. The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. Pharmacogenetics. 1999;9:37\u201342. https:\/\/doi.org\/10.1097\/00008571-199902000-00006.","journal-title":"Pharmacogenetics"},{"key":"959_CR8","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/s0016-5085(00)70354-4","volume":"118","author":"JF Colombel","year":"2000","unstructured":"Colombel JF, Ferrari N, Debuysere H, Marteau P, Gendre JP, Bonaz B, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn\u2019s disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 2000;118:1025\u201330. https:\/\/doi.org\/10.1016\/s0016-5085(00)70354-4.","journal-title":"Gastroenterology"},{"key":"959_CR9","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1097\/fpc.0000000000000411","volume":"30","author":"GMA Ferreira","year":"2020","unstructured":"Ferreira GMA, Ribeiro Elias AB, Nascimento J, Monteiro WM, Melo GC, Baia-da-Silva DC, et al. Pharmacogenomics of thiopurines: distribution of TPMT and NUDT15 polymorphisms in the Brazilian Amazon. Pharmacogenet Genomics. 2020;30:184\u20139. https:\/\/doi.org\/10.1097\/fpc.0000000000000411.","journal-title":"Pharmacogenet Genomics"},{"key":"959_CR10","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.2147\/tcrm.S432856","volume":"19","author":"J Gallardo-C\u00f3ndor","year":"2023","unstructured":"Gallardo-C\u00f3ndor J, Naranjo P, Atarihuana S, Coello D, Guevara-Ram\u00edrez P, Flores-Espinoza R, et al. Population-specific distribution of TPMT deficiency variants and ancestry proportions in Ecuadorian ethnic groups: towards personalized medicine. Ther Clin Risk Manag. 2023;19:1005\u201318. https:\/\/doi.org\/10.2147\/tcrm.S432856.","journal-title":"Ther Clin Risk Manag"},{"key":"959_CR11","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1002\/cpt.1322","volume":"105","author":"R Huddart","year":"2019","unstructured":"Huddart R, Fohner AE, Whirl-Carrillo M, Wojcik GL, Gignoux CR, Popejoy AB, et al. Standardized biogeographic grouping system for annotating populations in pharmacogenetic research. Clin Pharmacol Ther. 2019;105:1256\u201362. https:\/\/doi.org\/10.1002\/cpt.1322.","journal-title":"Clin Pharmacol Ther"},{"key":"959_CR12","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1002\/ibd.21221","volume":"16","author":"B Jharap","year":"2010","unstructured":"Jharap B, Seinen ML, de Boer NK, van Ginkel JR, Linskens RK, Kneppelhout JC, et al. Thiopurine therapy in inflammatory bowel disease patients: analyses of two 8-year intercept cohorts. Inflamm Bowel Dis. 2010;16:1541\u20139. https:\/\/doi.org\/10.1002\/ibd.21221.","journal-title":"Inflamm Bowel Dis"},{"key":"959_CR13","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1007\/s00535-018-1486-7","volume":"53","author":"Y Kakuta","year":"2018","unstructured":"Kakuta Y, Kawai Y, Okamoto D, Takagawa T, Ikeya K, Sakuraba H, et al. NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study. J Gastroenterol. 2018;53:1065\u201378. https:\/\/doi.org\/10.1007\/s00535-018-1486-7.","journal-title":"J Gastroenterol"},{"key":"959_CR14","doi-asserted-by":"publisher","first-page":"100436","DOI":"10.1016\/j.dmpk.2021.100436","volume":"43","author":"K Khaeso","year":"2022","unstructured":"Khaeso K, Komvilaisak P, Chainansamit SO, Nakkam N, Suwannaying K, Kuwatjanakul P, et al. NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine. Drug Metab Pharmacokinet. 2022;43:100436. https:\/\/doi.org\/10.1016\/j.dmpk.2021.100436.","journal-title":"Drug Metab Pharmacokinet"},{"key":"959_CR15","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1097\/00043426-200206000-00006","volume":"24","author":"SK Kham","year":"2002","unstructured":"Kham SK, Tan PL, Tay AH, Heng CK, Yeoh AE, Quah TC. Thiopurine methyltransferase polymorphisms in a multiracial Asian population and children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2002;24:353\u20139. https:\/\/doi.org\/10.1097\/00043426-200206000-00006.","journal-title":"J Pediatr Hematol Oncol"},{"key":"959_CR16","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.bbapap.2019.01.006","volume":"1867","author":"P Man","year":"2019","unstructured":"Man P, F\u00e1bry M, Sieglov\u00e1 I, Kavan D, Nov\u00e1k P, Hn\u00edzda A. Thiopurine intolerance-causing mutations in NUDT15 induce temperature-dependent destabilization of the catalytic site. Biochim Biophys Acta Proteins Proteom. 2019;1867:376\u201381. https:\/\/doi.org\/10.1016\/j.bbapap.2019.01.006.","journal-title":"Biochim Biophys Acta Proteins Proteom"},{"key":"959_CR17","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/sj.leu.2401723","volume":"14","author":"HL McLeod","year":"2000","unstructured":"McLeod HL, Krynetski EY, Relling MV, Evans WE. Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia. 2000;14:567\u201372. https:\/\/doi.org\/10.1038\/sj.leu.2401723.","journal-title":"Leukemia"},{"key":"959_CR18","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1097\/00008571-199912000-00012","volume":"9","author":"HL McLeod","year":"1999","unstructured":"McLeod HL, Pritchard SC, Githang\u2019a J, Indalo A, Ameyaw MM, Powrie RH, et al. Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals. Pharmacogenetics. 1999;9:773\u20136. https:\/\/doi.org\/10.1097\/00008571-199912000-00012.","journal-title":"Pharmacogenetics"},{"key":"959_CR19","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/ng.3508","volume":"48","author":"T Moriyama","year":"2016","unstructured":"Moriyama T, Nishii R, Perez-Andreu V, Yang W, Klussmann FA, Zhao X, et al. NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity. Nat Genet. 2016;48:367\u201373. https:\/\/doi.org\/10.1038\/ng.3508.","journal-title":"Nat Genet"},{"key":"959_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.clinbiochem.2021.02.007","volume":"92","author":"AM Moyer","year":"2021","unstructured":"Moyer AM. NUDT15: a bench to bedside success story. Clin Biochem. 2021;92:1\u20138. https:\/\/doi.org\/10.1016\/j.clinbiochem.2021.02.007.","journal-title":"Clin Biochem"},{"key":"959_CR21","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1007\/s00228-007-0310-8","volume":"63","author":"E Oliveira","year":"2007","unstructured":"Oliveira E, Quental S, Alves S, Amorim A, Prata MJ. Do the distribution patterns of polymorphisms at the thiopurine S-methyltransferase locus in sub-Saharan populations need revision? Hints from Cabinda and Mozambique. Eur J Clin Pharmacol. 2007;63:703\u20136. https:\/\/doi.org\/10.1007\/s00228-007-0310-8.","journal-title":"Eur J Clin Pharmacol"},{"key":"959_CR22","doi-asserted-by":"publisher","first-page":"1359570","DOI":"10.3389\/fphar.2024.1359570","volume":"15","author":"JA Perini","year":"2024","unstructured":"Perini JA, Basta PC, Suarez-Kurtz G. NUDT15 and TPMT polymorphisms in three distinct native populations of the Brazilian Amazon. Front Pharmacol. 2024;15:1359570. https:\/\/doi.org\/10.3389\/fphar.2024.1359570.","journal-title":"Front Pharmacol"},{"key":"959_CR23","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1002\/cpt.1304","volume":"105","author":"MV Relling","year":"2019","unstructured":"Relling MV, Schwab M, Whirl-Carrillo M, Suarez-Kurtz G, Pui CH, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update. Clin Pharmacol Ther. 2019;105:1095\u2013105. https:\/\/doi.org\/10.1002\/cpt.1304.","journal-title":"Clin Pharmacol Ther"},{"key":"959_CR24","doi-asserted-by":"publisher","first-page":"e0231651","DOI":"10.1371\/journal.pone.0231651","volume":"15","author":"JCG Rodrigues","year":"2020","unstructured":"Rodrigues JCG, Souza TP, Pastana LF, Ribeiro Dos Santos AM, Fernandes MR, Pinto P, et al. Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil. PLoS ONE. 2020;15:e0231651. https:\/\/doi.org\/10.1371\/journal.pone.0231651.","journal-title":"PLoS ONE"},{"key":"959_CR25","doi-asserted-by":"publisher","first-page":"328","DOI":"10.5217\/ir.2017.15.3.328","volume":"15","author":"T Sato","year":"2017","unstructured":"Sato T, Takagawa T, Kakuta Y, Nishio A, Kawai M, Kamikozuru K, et al. NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases. Intest Res. 2017;15:328\u201337. https:\/\/doi.org\/10.5217\/ir.2017.15.3.328.","journal-title":"Intest Res"},{"key":"959_CR26","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1111\/j.1365-2125.2004.02112.x","volume":"58","author":"S Srimartpirom","year":"2004","unstructured":"Srimartpirom S, Tassaneeyakul W, Kukongviriyapan V, Tassaneeyakul W. Thiopurine S-methyltransferase genetic polymorphism in the Thai population. Br J Clin Pharmacol. 2004;58:66\u201370. https:\/\/doi.org\/10.1111\/j.1365-2125.2004.02112.x.","journal-title":"Br J Clin Pharmacol"},{"key":"959_CR27","doi-asserted-by":"publisher","first-page":"118","DOI":"10.3389\/fphar.2010.00118","volume":"1","author":"G Suarez-Kurtz","year":"2010","unstructured":"Suarez-Kurtz G. Pharmacogenetics in the Brazilian population. Front Pharmacol. 2010;1:118. https:\/\/doi.org\/10.3389\/fphar.2010.00118.","journal-title":"Front Pharmacol"},{"key":"959_CR28","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/tpj.2017.12","volume":"18","author":"Y Tanaka","year":"2018","unstructured":"Tanaka Y, Nakadate H, Kondoh K, Nakamura K, Koh K, Manabe A. Interaction between NUDT15 and ABCC4 variants enhances intolerability of 6-mercaptopurine in Japanese patients with childhood acute lymphoblastic leukemia. Pharmacogenomics J. 2018;18:275\u201380. https:\/\/doi.org\/10.1038\/tpj.2017.12.","journal-title":"Pharmacogenomics J"},{"key":"959_CR29","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1016","author":"R Tremmel","year":"2024","unstructured":"Tremmel R, Zhou Y, Camara MD, Laarif S, Eliasson E, Lauschke VM. PharmFreq: a comprehensive atlas of ethnogeographic allelic variation in clinically important pharmacogenes. Nucleic Acids Res. 2024. https:\/\/doi.org\/10.1093\/nar\/gkae1016.","journal-title":"Nucleic Acids Res"},{"key":"959_CR30","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1002\/cpt.2716","volume":"112","author":"CW Wang","year":"2022","unstructured":"Wang CW, Chi MH, Tsai TF, Yu KH, Kao HW, Chen HC, et al. Implementation of NUDT15 genotyping to prevent Azathioprine-induced leukopenia for patients with autoimmune disorders in Chinese population. Clin Pharmacol Ther. 2022;112:1079\u201387. https:\/\/doi.org\/10.1002\/cpt.2716.","journal-title":"Clin Pharmacol Ther"},{"key":"959_CR31","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1200\/jco.2014.59.4671","volume":"33","author":"JJ Yang","year":"2015","unstructured":"Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, et al. Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J Clin Oncol. 2015;33:1235\u201342. https:\/\/doi.org\/10.1200\/jco.2014.59.4671.","journal-title":"J Clin Oncol"},{"key":"959_CR32","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1038\/ng.3060","volume":"46","author":"SK Yang","year":"2014","unstructured":"Yang SK, Hong M, Baek J, Choi H, Zhao W, Jung Y, et al. A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nat Genet. 2014;46:1017\u201320. https:\/\/doi.org\/10.1038\/ng.3060.","journal-title":"Nat Genet"},{"key":"959_CR33","doi-asserted-by":"publisher","first-page":"608","DOI":"10.7326\/0003-4819-126-8-199704150-00003","volume":"126","author":"CR Yates","year":"1997","unstructured":"Yates CR, Krynetski EY, Loennechen T, Fessing MY, Tai HL, Pui CH, et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med. 1997;126:608\u201314. https:\/\/doi.org\/10.7326\/0003-4819-126-8-199704150-00003.","journal-title":"Ann Intern Med"},{"key":"959_CR34","first-page":"3665","volume":"125","author":"Q Zhu","year":"2012","unstructured":"Zhu Q, Cao Q. Thiopurine methyltransferase gene polymorphisms and activity in Chinese patients with inflammatory bowel disease treated with azathioprine. Chin Med J (Engl). 2012;125:3665\u201370.","journal-title":"Chin Med J (Engl)"},{"key":"959_CR35","doi-asserted-by":"publisher","first-page":"100119","DOI":"10.1016\/j.dmd.2025.100119","volume":"53","author":"X Zhu","year":"2025","unstructured":"Zhu X, Wang XD, Xuan QL, Guan SX, Guan YP, Gao X, et al. Establishment of a novel predictive model for thiopurine-induced leucopenia based on the polymorphisms in the DNA-thioguanine nucleotide metabolite pathway in Chinese patients with inflammatory bowel disease. Drug Metab Dispos. 2025;53:100119. https:\/\/doi.org\/10.1016\/j.dmd.2025.100119.","journal-title":"Drug Metab Dispos"}],"container-title":["Human Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40246-026-00959-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40246-026-00959-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40246-026-00959-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T12:07:25Z","timestamp":1775822845000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40246-026-00959-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,4]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["959"],"URL":"https:\/\/doi.org\/10.1186\/s40246-026-00959-2","relation":{},"ISSN":["1479-7364"],"issn-type":[{"value":"1479-7364","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,4]]},"assertion":[{"value":"19 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 April 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":"VML is co-founder, CEO and shareholder of HepaPredict AB, as well as co-founder and shareholder of Shanghai Hepo Biotechnology Ltd. All other authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"68"}}