{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:11:21Z","timestamp":1790633481544,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The SLC25A26 gene encodes a mitochondrial inner membrane carrier that transports S-adenosylmethionine (SAM) into the mitochondrial matrix in exchange for S-adenosylhomocysteine (SAH). SAM is the predominant methyl-group donor for most cellular methylation processes, of which SAH is produced as a by-product. Pathogenic, biallelic SLC25A26 variants are a recognized cause of mitochondrial disease in children, with a severe neonatal onset caused by decreased SAM transport activity. Here, we describe two, unrelated adult cases, one of whom presented with recurrent episodes of severe abdominal pain and metabolic decompensation with lactic acidosis. Both patients had exercise intolerance and mitochondrial myopathy associated with biallelic variants in SLC25A26, which led to marked respiratory chain deficiencies and mitochondrial histopathological abnormalities in skeletal muscle that are comparable to those previously described in early-onset cases. We demonstrate using both mouse and fruit fly models that impairment of SAH, rather than SAM, transport across the mitochondrial membrane is likely the cause of this milder, late-onset phenotype. Our findings associate a novel pathomechanism with a known disease-causing protein and highlight the quests of precision medicine in optimizing diagnosis, therapeutic intervention and prognosis.<\/jats:p>","DOI":"10.1093\/hmg\/ddac002","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T20:12:19Z","timestamp":1641413539000},"page":"2049-2062","source":"Crossref","is-referenced-by-count":17,"title":["Pathogenic SLC25A26 variants impair SAH transport activity causing mitochondrial disease"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4604-6170","authenticated-orcid":false,"given":"Florian A","family":"Rosenberger","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institute , 171 65 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia Xin","family":"Tang","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"},{"name":"Newcastle University , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Sergeant","sequence":"additional","affiliation":[{"name":"Oxford Regional Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust , Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco F","family":"Moedas","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institute , 171 65 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte M","family":"Zierz","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"},{"name":"Newcastle University , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institute , 171 65 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conrad","family":"Smith","sequence":"additional","affiliation":[{"name":"Oxford Regional Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust , Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Oxford University Hospitals NHS Foundation Trust , Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishan","family":"Guha","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Oxford University Hospitals NHS Foundation Trust , Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sila","family":"Hopton","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"},{"name":"Newcastle University , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"},{"name":"NHS Highly Specialised Services for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Falkous","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"},{"name":"Newcastle University , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"},{"name":"NHS Highly Specialised Services for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Lam","sequence":"additional","affiliation":[{"name":"Neurometabolic Unit, Institute of Neurology, Queen Square House , London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Pyle","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"},{"name":"Newcastle University , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Poulton","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford , Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e1inne S","family":"Gorman","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"},{"name":"Newcastle University , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"},{"name":"NHS Highly Specialised Services for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W","family":"Taylor","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"},{"name":"Newcastle University , Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, , Newcastle upon Tyne NE2 4HH, UK"},{"name":"NHS Highly Specialised Services for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0418-1673","authenticated-orcid":false,"given":"Christoph","family":"Freyer","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institute , 171 65 Stockholm, Sweden"},{"name":"Centre for Inherited Metabolic Diseases, Karolinska University Hospital , 171 76 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wredenberg","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institute , 171 65 Stockholm, Sweden"},{"name":"Centre for Inherited Metabolic Diseases, Karolinska University Hospital , 171 76 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"2023011114293213100_ref1","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.tibs.2019.11.001","article-title":"The SLC25 mitochondrial carrier family: structure and mechanism","volume":"45","author":"Ruprecht","year":"2019","journal-title":"Trends Biochem. Sci."},{"key":"2023011114293213100_ref2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.mam.2012.05.005","article-title":"The mitochondrial transporter family SLC25: Identification, properties and physiopathology","volume":"34","author":"Palmieri","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"2023011114293213100_ref3","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1152\/physiol.00009.2020","article-title":"The SLC25 carrier family: important transport proteins in mitochondrial physiology and pathology","volume":"35","author":"Kunji","year":"2020","journal-title":"Physiology"},{"key":"2023011114293213100_ref4","first-page":"655","article-title":"Diseases caused by mutations in mitochondrial carrier genes SLC25: a review","volume":"10","author":"Palmieri","year":"2020","journal-title":"Biomol. Ther."},{"key":"2023011114293213100_ref5","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1126\/science.289.5480.782","article-title":"Role of adenine nucleotide translocator 1 in mtDNA maintenance","volume":"289","author":"Kaukonen","year":"2000","journal-title":"Science"},{"key":"2023011114293213100_ref6","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/hmg\/ddh108","article-title":"Mutations in AAC2, equivalent to human adPEO-associated ANT1 mutations, lead to defective oxidative phosphorylation in Saccharomyces cerevisiae and affect mitochondrial DNA stability","volume":"13","author":"Fontanesi","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"2023011114293213100_ref7","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1093\/hmg\/ddi341","article-title":"Complete loss-of-function of the heart\/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy","volume":"14","author":"Palmieri","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"2023011114293213100_ref8","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.ajhg.2016.08.014","article-title":"Recurrent de novo dominant mutations in SLC25A4 cause severe early-onset mitochondrial disease and loss of mitochondrial DNA copy number","volume":"99","author":"Thompson","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"2023011114293213100_ref9","doi-asserted-by":"crossref","DOI":"10.1212\/NXG.0000000000000256","article-title":"Expanding the phenotype of de novo SLC25A4-linked mitochondrial disease to include mild myopathy","volume":"4","author":"King","year":"2018","journal-title":"Neurology Genetics"},{"key":"2023011114293213100_ref10","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1056\/NEJMoa0900591","article-title":"AGC1 deficiency associated with global cerebral hypomyelination","volume":"361","author":"Wibom","year":"2009","journal-title":"New Engl. J. Med."},{"key":"2023011114293213100_ref11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/8904_2013_287","article-title":"AGC1 deficiency causes infantile epilepsy, abnormal myelination, and reduced N-acetylaspartate","volume":"14","author":"Falk","year":"2014","journal-title":"JIMD Reports"},{"key":"2023011114293213100_ref12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/9667","article-title":"The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein","volume":"22","author":"Kobayashi","year":"1999","journal-title":"Nat. Genet."},{"key":"2023011114293213100_ref13","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ymgme.2019.06.004","article-title":"Current treatment for citrin deficiency during NICCD and adaptation\/compensation stages: strategy to prevent CTLN2","volume":"127","author":"Okano","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"2023011114293213100_ref14","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1042\/bj20031664","article-title":"Identification of the human mitochondrial S-adenosylmethionine transporter: bacterial expression, reconstitution, functional characterization and tissue distribution","volume":"379","author":"Agrimi","year":"2004","journal-title":"Biochem. J."},{"key":"2023011114293213100_ref15","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.ajhg.2015.09.013","article-title":"Intra-mitochondrial methylation deficiency due to mutations in SLC25A26","volume":"97","author":"Kishita","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"2023011114293213100_ref16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"one-carbon metabolism in health and disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"2023011114293213100_ref17","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.tibs.2004.03.007","article-title":"S-adenosylmethionine: nothing goes to waste","volume":"29","author":"Fontecave","year":"2004","journal-title":"Trends Biochem. Sci."},{"issue":"M110","key":"2023011114293213100_ref18","article-title":"Uncovering the human methyltransferasome*","volume":"10","author":"Petrossian","year":"2011","journal-title":"Mol. Cell. Proteomics"},{"key":"2023011114293213100_ref19","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.tibs.2013.02.004","article-title":"Protein methylation at the surface and buried deep: thinking outside the histone box","volume":"38","author":"Clarke","year":"2013","journal-title":"Trends Biochem. Sci."},{"key":"2023011114293213100_ref20","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1004110","article-title":"NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly","volume":"10","author":"Metodiev","year":"2014","journal-title":"PLoS Genet."},{"key":"2023011114293213100_ref21","doi-asserted-by":"crossref","first-page":"13382","DOI":"10.1021\/ja075520+","article-title":"A methyl group controls conformational equilibrium in human mitochondrial tRNA Lys","volume":"129","author":"Voigts-Hoffmann","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"2023011114293213100_ref22","doi-asserted-by":"crossref","first-page":"11583","DOI":"10.1093\/nar\/gks910","article-title":"A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase\u2014extensive moonlighting in mitochondrial tRNA biogenesis","volume":"40","author":"Vilardo","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023011114293213100_ref23","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1038\/s41467-020-18068-6","article-title":"Complete chemical structures of human mitochondrial tRNAs","volume":"11","author":"Suzuki","year":"2020","journal-title":"Nat. Commun."},{"key":"2023011114293213100_ref24","doi-asserted-by":"crossref","first-page":"7346","DOI":"10.1093\/nar\/gku390","article-title":"A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs","volume":"42","author":"Suzuki","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2023011114293213100_ref25","doi-asserted-by":"crossref","first-page":"15253","DOI":"10.1073\/pnas.1210688109","article-title":"Structure of the human MTERF4\u2013NSUN4 protein complex that regulates mitochondrial ribosome biogenesis","volume":"109","author":"Sp\u00e5hr","year":"2012","journal-title":"Proc. Natl. Acad. Sci."},{"key":"2023011114293213100_ref26","doi-asserted-by":"crossref","first-page":"33016","DOI":"10.1074\/jbc.M113.518803","article-title":"NDUFAF7 methylates Arginine 85 in the NDUFS2 subunit of human complex I","volume":"288","author":"Rhein","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2023011114293213100_ref27","doi-asserted-by":"crossref","first-page":"24640","DOI":"10.1074\/jbc.M114.580464","article-title":"Human METTL20 methylates lysine residues adjacent to the recognition loop of the electron transfer flavoprotein in mitochondria","volume":"289","author":"Rhein","year":"2014","journal-title":"J. Biol. Chem."},{"key":"2023011114293213100_ref28","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1002\/1873-3468.12649","article-title":"Human METTL12 is a mitochondrial methyltransferase that modifies citrate synthase","volume":"591","author":"Rhein","year":"2017","journal-title":"FEBS Lett."},{"key":"2023011114293213100_ref29","doi-asserted-by":"crossref","first-page":"11654","DOI":"10.1074\/jbc.RA119.009045","article-title":"Human FAM173A is a mitochondrial lysine-specific methyltransferase that targets adenine nucleotide translocase and affects mitochondrial respiration","volume":"294","author":"Ma\u0142ecki","year":"2019","journal-title":"J. Biol. Chem."},{"key":"2023011114293213100_ref30","doi-asserted-by":"crossref","first-page":"9182","DOI":"10.1074\/jbc.272.14.9182","article-title":"Characterization of the COQ5 gene from Saccharomyces cerevisiae evidence for a C-methyltransferase in ubiquinone biosynthesis","volume":"272","author":"Barkovich","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2023011114293213100_ref31","doi-asserted-by":"crossref","first-page":"16636","DOI":"10.1016\/S0021-9258(18)55349-7","article-title":"Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolation and sequence of COQ3, the 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase gene","volume":"266","author":"Clarke","year":"1991","journal-title":"J. Biol. Chem."},{"key":"2023011114293213100_ref32","doi-asserted-by":"crossref","first-page":"15166","DOI":"10.1021\/bi002060n","article-title":"Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein","volume":"39","author":"Miller","year":"2000","journal-title":"Biochemistry"},{"key":"2023011114293213100_ref33","doi-asserted-by":"crossref","first-page":"eabf0717","DOI":"10.1126\/sciadv.abf0717","article-title":"The one-carbon pool controls mitochondrial energy metabolism via complex I and iron-sulfur clusters","volume":"7","author":"Schober","year":"2021","journal-title":"Sci. Adv."},{"key":"2023011114293213100_ref34","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"2023011114293213100_ref35","doi-asserted-by":"crossref","first-page":"15037","DOI":"10.1038\/srep15037","article-title":"A novel immunofluorescent assay to investigate oxidative phosphorylation deficiency in mitochondrial myopathy: understanding mechanisms and improving diagnosis","volume":"5","author":"Rocha","year":"2015","journal-title":"Sci. Rep."},{"key":"2023011114293213100_ref36","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/0014-5793(82)80648-0","article-title":"Internal sequence repeats and the path of polypeptide in mitochondrial ADP\/ATP translocase","volume":"144","author":"Saraste","year":"1982","journal-title":"FEBS Lett."},{"key":"2023011114293213100_ref37","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nature02056","article-title":"Structure of mitochondrial ADP\/ATP carrier in complex with carboxyatractyloside","volume":"426","author":"Pebay-Peyroula","year":"2003","journal-title":"Nature"},{"key":"2023011114293213100_ref38","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.bbamem.2018.01.017","article-title":"Cardiolipin dynamics and binding to conserved residues in the mitochondrial ADP\/ATP carrier","volume":"1860","author":"Duncan","year":"2018","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"2023011114293213100_ref39","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/embor.2009.170","article-title":"Missed threads","volume":"10","author":"Baralle","year":"2009","journal-title":"EMBO Rep."},{"key":"2023011114293213100_ref40","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.bbapap.2008.04.016","article-title":"Acetylation of N-terminal valine of glycine N-methyltransferase affects enzyme inhibition by folate","volume":"1784","author":"Luka","year":"2008","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"2023011114293213100_ref41","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1126\/science.aao3265","article-title":"SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway","volume":"358","author":"Gu","year":"2017","journal-title":"Science"},{"key":"2023011114293213100_ref42","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1093\/nar\/gkz1128","article-title":"mitoXplorer, a visual data mining platform to systematically analyze and visualize mitochondrial expression dynamics and mutations","volume":"48","author":"Yim","year":"2019","journal-title":"Nucleic Acids Res."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddac002\/42417460\/ddac002.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/12\/2049\/48075993\/ddac002.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/12\/2049\/48075993\/ddac002.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T17:47:38Z","timestamp":1673459258000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/31\/12\/2049\/6504746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,13]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,1,13]]},"published-print":{"date-parts":[[2022,6,22]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddac002","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,6,15]]},"published":{"date-parts":[[2022,1,13]]}}}