{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T12:13:01Z","timestamp":1779106381672,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,14]]},"group-title":"Molecular Biology","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["5TL1DK139565-03"],"award-info":[{"award-number":["5TL1DK139565-03"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"United States Public Health Service","award":["R01HD113778"],"award-info":[{"award-number":["R01HD113778"]}]},{"name":"United States Public Health Service","award":["R21OD037868"],"award-info":[{"award-number":["R21OD037868"]}]},{"name":"United States Public Health Service","award":["R21TR004262"],"award-info":[{"award-number":["R21TR004262"]}]},{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["DK064324"],"award-info":[{"award-number":["DK064324"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a rare condition causing nephrotic syndrome, neuropathy, and other manifestations. SPLIS is caused by mutations in\n                  <jats:italic>SGPL1<\/jats:italic>\n                  , which encodes sphingosine-1-phosphate lyase (SPL), a pyridoxal 5\u2019-phosphate (PLP)-dependent enzyme needed to degrade the bioactive sphingolipid sphingosine-1-phosphate (S1P). Supplementation with the PLP precursor pyridoxine benefits some individuals with PLP-dependent enzymopathies. We sought to establish whether pyridoxine has therapeutic activity in SPLIS. Neurological improvement, plasma S1P normalization, and increased SPL activity in patient-derived fibroblasts were observed after pyridoxine supplementation in a patient with R222Q-variant SPLIS. Additionally, PLP dose-dependently augmented recombinant R222Q-variant SPL activity. To further explore pyridoxine\u2019s effects, gene editing was employed to create an R222Q-variant SPLIS mouse model. SPL\n                  <jats:sup>R222Q<\/jats:sup>\n                  mice fed pyridoxine-enriched chow lacked obvious phenotypes. However, SPL inactivation, S1P accumulation, wasting, anemia, proteinuria, and glomerulosclerosis developed in SPL\n                  <jats:sup>R222Q<\/jats:sup>\n                  but not WT mice fed chow with reduced pyridoxine. Ultrastructural analysis and super-resolution microscopy showed podocyte loss and foot process effacement. Transcriptional profiling revealed a pattern of cytokine upregulation and extracellular matrix remodeling. Inhibiting S1P production prevented nephrosis in SPL\n                  <jats:sup>R222Q<\/jats:sup>\n                  mice fed chow lacking pyridoxine. Our findings establish a novel SPLIS mouse model that recapitulates R222Q-variant SPLIS, demonstrates its responsiveness to pyridoxine, and implicates S1P in its pathophysiology.\n                <\/jats:p>","DOI":"10.64898\/2026.05.11.724358","type":"posted-content","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T19:10:19Z","timestamp":1778785819000},"source":"Crossref","is-referenced-by-count":0,"title":["Pyridoxine supplementation confers protection against\n                  <i>\n                    SGPL1\n                    <sup>R222Q<\/sup>\n                  <\/i>\n                  variant sphingosine phosphate lyase insufficiency syndrome"],"prefix":"10.64898","author":[{"given":"Ranjha","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Pediatrics, UCSF School of Medicine, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria L.","family":"Allende","sequence":"additional","affiliation":[{"name":"Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehtesham","family":"Khalid","sequence":"additional","affiliation":[{"name":"Ochsner Clinical School \/ University of Queensland (Australia) and Ochsner Health, New Orleans, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UCSF School of Medicine, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Everett","family":"Stone","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Texas, Austin, TX, USA; Department of Oncology, University of Texas Dell Medical School, LiveSTRONG Cancer Institutes, Austin, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Rodnick-Smith","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Texas, Austin, TX, USA; Department of Oncology, University of Texas Dell Medical School, LiveSTRONG Cancer Institutes, Austin, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Izuhara","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience and Department of Medicine, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vadym","family":"Buncha","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience and Department of Medicine, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgina","family":"Gyarmati","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience and Department of Medicine, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4092-6185","authenticated-orcid":false,"given":"Janos","family":"Peti-Peterdi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience and Department of Medicine, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranya","family":"Al-Khaledy","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Texas, Austin, TX, USA; Department of Oncology, University of Texas Dell Medical School, LiveSTRONG Cancer Institutes, Austin, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey B.","family":"Hodgin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gizachew","family":"Tassew","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UCSF School of Medicine, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Babak","family":"Oskouian","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UCSF School of Medicine, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UCSF School of Medicine, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard L.","family":"Proia","sequence":"additional","affiliation":[{"name":"Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie D.","family":"Saba","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UCSF School of Medicine, San Francisco, CA, USA"},{"name":"Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026051804202117000_2026.05.11.724358v1.1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89626"},{"key":"2026051804202117000_2026.05.11.724358v1.2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90171"},{"key":"2026051804202117000_2026.05.11.724358v1.3","doi-asserted-by":"crossref","unstructured":"Sedillo J , Badduke C , Schrodi S , Scaria V , Onat O , Alfadhel M , et al. Prevalence estimate of sphingosine phosphate lyase insufficiency syndrome in worldwide and select populations. Genetics in Medicine Open. 2024;2.","DOI":"10.1016\/j.gimo.2023.100840"},{"key":"2026051804202117000_2026.05.11.724358v1.4","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-024-03311-w"},{"key":"2026051804202117000_2026.05.11.724358v1.5","doi-asserted-by":"crossref","unstructured":"Pournasiri Z , Madani A , Nazarpack F , Sayer JA , Chavoshzadeh Z , Nili F , et al. Sphingosine phosphate lyase insufficiency syndrome: a systematic review. World J Pediatr. 2022.","DOI":"10.1007\/s12519-022-00615-4"},{"key":"2026051804202117000_2026.05.11.724358v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(00)11087-0"},{"key":"2026051804202117000_2026.05.11.724358v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/ng1922"},{"key":"2026051804202117000_2026.05.11.724358v1.8","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M004374"},{"key":"2026051804202117000_2026.05.11.724358v1.9","doi-asserted-by":"crossref","unstructured":"Cartier A , and Hla T . Sphingosine 1-phosphate: Lipid signaling in pathology and therapy. Science. 2019;366(6463).","DOI":"10.1126\/science.aar5551"},{"issue":"4","key":"2026051804202117000_2026.05.11.724358v1.10","doi-asserted-by":"crossref","first-page":"100351","DOI":"10.1016\/j.jlr.2023.100351","article-title":"Ichthyosis linked to sphingosine 1-phosphate lyase insufficiency is due to aberrant sphingolipid and calcium regulation","volume":"64","year":"2023","journal-title":"J Lipid Res"},{"key":"2026051804202117000_2026.05.11.724358v1.11","doi-asserted-by":"crossref","unstructured":"Maharaj A , Williams J , Bradshaw T , Guran T , Braslavsky D , Casas J , et al. Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction. J Steroid Biochem Mol Biol. 2020;202:105730.","DOI":"10.1016\/j.jsbmb.2020.105730"},{"key":"2026051804202117000_2026.05.11.724358v1.12","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2017.1291471"},{"key":"2026051804202117000_2026.05.11.724358v1.13","doi-asserted-by":"crossref","unstructured":"Mitroi DN , Deutschmann AU , Raucamp M , Karunakaran I , Glebov K , Hans M , et al. Sphingosine 1-phosphate lyase ablation disrupts presynaptic architecture and function via an ubiquitin-proteasome mediated mechanism. Sci Rep. 2016;6:37064.","DOI":"10.1038\/srep37064"},{"key":"2026051804202117000_2026.05.11.724358v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.01.038"},{"key":"2026051804202117000_2026.05.11.724358v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.06.012"},{"key":"2026051804202117000_2026.05.11.724358v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2011.02.009"},{"key":"2026051804202117000_2026.05.11.724358v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12060"},{"key":"2026051804202117000_2026.05.11.724358v1.18","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.06820613"},{"issue":"3","key":"2026051804202117000_2026.05.11.724358v1.19","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.clinbiochem.2013.11.021","article-title":"The chaperone role of the pyridoxal 5\u2019-phosphate and its implications for rare diseases involving B6-dependent enzymes","volume":"47","year":"2014","journal-title":"Clin Biochem"},{"key":"2026051804202117000_2026.05.11.724358v1.20","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12238"},{"key":"2026051804202117000_2026.05.11.724358v1.21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004112"},{"key":"2026051804202117000_2026.05.11.724358v1.22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.081489"},{"key":"2026051804202117000_2026.05.11.724358v1.23","doi-asserted-by":"crossref","unstructured":"Zhao P , Tassew GB , Lee JY , Oskouian B , Munoz DP , Hodgin JB , et al. Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome. JCI Insight. 2021;6(8).","DOI":"10.1172\/jci.insight.145936"},{"key":"2026051804202117000_2026.05.11.724358v1.24","unstructured":"Nutrition SoLA. In: Sciences NAo ed. Nutrient Requirements of Laboratory Animals. National Academies Press; 1995:80\u2013115."},{"key":"2026051804202117000_2026.05.11.724358v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.259"},{"key":"2026051804202117000_2026.05.11.724358v1.26","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2287930"},{"key":"2026051804202117000_2026.05.11.724358v1.27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.19.11272"},{"key":"2026051804202117000_2026.05.11.724358v1.28","doi-asserted-by":"crossref","unstructured":"Romero DJ , Pescio LG , Santacreu BJ , Mosca JM , Sterin-Speziale NB , and Favale NO . Sphingosine-1-phosphate receptor 2 plays a dual role depending on the stage of cell differentiation in renal epithelial cells. Life Sci. 2023;316:121404.","DOI":"10.1016\/j.lfs.2023.121404"},{"key":"2026051804202117000_2026.05.11.724358v1.29","doi-asserted-by":"crossref","unstructured":"Lu Q , Tan M , Hou Q , Wang M , and Dai C . PP2A Catalytic Subunit alpha promotes fibroblast activation and kidney fibrosis via ERK pathway. Cell Signal. 2022;90:110187.","DOI":"10.1016\/j.cellsig.2021.110187"},{"key":"2026051804202117000_2026.05.11.724358v1.30","doi-asserted-by":"crossref","unstructured":"Imeri F , Stepanovska Tanturovska B , Manaila R , Pavenstadt H , Pfeilschifter J , and Huwiler A . Loss of S1P lyase expression in human podocytes causes a reduction in nephrin expression that involves PKCdelta activation. Int J Mol Sci. 2023;24(4).","DOI":"10.3390\/ijms24043267"},{"key":"2026051804202117000_2026.05.11.724358v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00590-z"},{"key":"2026051804202117000_2026.05.11.724358v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2250"},{"key":"2026051804202117000_2026.05.11.724358v1.33","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74188"},{"key":"2026051804202117000_2026.05.11.724358v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.11.013"},{"key":"2026051804202117000_2026.05.11.724358v1.35","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00034.2019"},{"key":"2026051804202117000_2026.05.11.724358v1.36","doi-asserted-by":"publisher","DOI":"10.1093\/NDT\/GFX246"},{"key":"2026051804202117000_2026.05.11.724358v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.05.022"},{"issue":"5","key":"2026051804202117000_2026.05.11.724358v1.38","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.cmet.2021.04.004","article-title":"KIM-1 mediates fatty acid uptake by renal tubular cells to promote progressive diabetic kidney disease","volume":"33","year":"2021","journal-title":"Cell Metab"},{"key":"2026051804202117000_2026.05.11.724358v1.39","doi-asserted-by":"crossref","unstructured":"Paquissi FC , and Abensur H . The Th17\/IL-17 axis and kidney diseases, with focus on lupus nephritis. Front Med (Lausanne ). 2021;8:654912.","DOI":"10.3389\/fmed.2021.654912"},{"key":"2026051804202117000_2026.05.11.724358v1.40","doi-asserted-by":"crossref","unstructured":"Steele H , Cheng J , Willicut A , Dell G , Breckenridge J , Culberson E , et al. TNF superfamily control of tissue remodeling and fibrosis. Front Immunol. 2023;14:1219907.","DOI":"10.3389\/fimmu.2023.1219907"},{"key":"2026051804202117000_2026.05.11.724358v1.41","doi-asserted-by":"crossref","unstructured":"Portilla D , Sabapathy V , and Chauss D . Role of local complement activation in kidney fibrosis and repair. J Clin Invest. 2025;135(12).","DOI":"10.1172\/JCI188345"},{"key":"2026051804202117000_2026.05.11.724358v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1995"},{"key":"2026051804202117000_2026.05.11.724358v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.09.007"},{"key":"2026051804202117000_2026.05.11.724358v1.44","doi-asserted-by":"crossref","unstructured":"Zhao C , Wang H , Xu C , Fang F , Gao L , Zhai N , et al. The critical role of the Hippo signaling pathway in renal fibrosis. Cell Signal. 2025;130:111661.","DOI":"10.1016\/j.cellsig.2025.111661"},{"key":"2026051804202117000_2026.05.11.724358v1.45","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-19-0394-6_1"},{"key":"2026051804202117000_2026.05.11.724358v1.46","doi-asserted-by":"crossref","unstructured":"Han YZ , Du BX , Zhu XY , Wang YZ , Zheng HJ , and Liu WJ . Lipid metabolism disorder in diabetic kidney disease. Front Endocrinol (Lausanne ). 2024;15:1336402.","DOI":"10.3389\/fendo.2024.1336402"},{"key":"2026051804202117000_2026.05.11.724358v1.47","doi-asserted-by":"crossref","unstructured":"Luo Z , Chen Z , Hu J , and Ding G . Interplay of lipid metabolism and inflammation in podocyte injury. Metabolism. 2024;150:155718.","DOI":"10.1016\/j.metabol.2023.155718"},{"key":"2026051804202117000_2026.05.11.724358v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2022.100279"},{"key":"2026051804202117000_2026.05.11.724358v1.49","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013060656"},{"key":"2026051804202117000_2026.05.11.724358v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.05.029"},{"issue":"4","key":"2026051804202117000_2026.05.11.724358v1.51","first-page":"360","article-title":"Over-the-counter medications in pregnancy","volume":"108","year":"2023","journal-title":"Am Fam Physician"},{"key":"2026051804202117000_2026.05.11.724358v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4274(86)90202-X"},{"key":"2026051804202117000_2026.05.11.724358v1.53","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-021-01013-9"},{"key":"2026051804202117000_2026.05.11.724358v1.54","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502207200"},{"key":"2026051804202117000_2026.05.11.724358v1.55","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M049759"},{"key":"2026051804202117000_2026.05.11.724358v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.05.012"},{"key":"2026051804202117000_2026.05.11.724358v1.57","doi-asserted-by":"publisher","DOI":"10.1159\/000315108"},{"key":"2026051804202117000_2026.05.11.724358v1.58","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.003506"},{"key":"2026051804202117000_2026.05.11.724358v1.59","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176709"},{"key":"2026051804202117000_2026.05.11.724358v1.60","doi-asserted-by":"crossref","unstructured":"Strub GM , Paillard M , Liang J , Gomez L , Allegood JC , Hait NC , et al. Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration. FASEB J. 2010:1\u201313.","DOI":"10.1096\/fj.10-167502"},{"key":"2026051804202117000_2026.05.11.724358v1.61","first-page":"e3779","article-title":"Skin punch biopsy explant culture for derivation of primary human fibroblasts","volume":"77","year":"2013","journal-title":"J Vis Exp"},{"key":"2026051804202117000_2026.05.11.724358v1.62","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.chemphyslip.2015.09.006","article-title":"A facile stable-isotope dilution method for determination of sphingosine phosphate lyase activity","volume":"194","year":"2016","journal-title":"Chem Phys Lipids"},{"issue":"5","key":"2026051804202117000_2026.05.11.724358v1.63","first-page":"469","article-title":"Sphingosine-1-phosphate in inflammatory bowel disease and colitis-associated colon cancer: the fat\u2019s in the fire","volume":"4","year":"2015","journal-title":"Transl Cancer Res"},{"key":"2026051804202117000_2026.05.11.724358v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2011.09.097"},{"key":"2026051804202117000_2026.05.11.724358v1.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.04.025"},{"key":"2026051804202117000_2026.05.11.724358v1.66","doi-asserted-by":"crossref","unstructured":"Khan R , Oskouian B , Lee JY , Hodgin JB , Yang Y , Tassew G , et al. AAV-SPL 2.0, a modified adeno-associated virus gene therapy agent for the treatment of sphingosine phosphate lyase insufficiency syndrome. Int J Mol Sci. 2023;24(21).","DOI":"10.3390\/ijms242115560"},{"key":"2026051804202117000_2026.05.11.724358v1.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0201-4"},{"key":"2026051804202117000_2026.05.11.724358v1.68","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.095"},{"key":"2026051804202117000_2026.05.11.724358v1.69","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026051804202117000_2026.05.11.724358v1.70","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"2026051804202117000_2026.05.11.724358v1.71","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.11.724358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:21:08Z","timestamp":1779103268000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.11.724358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":71,"URL":"https:\/\/doi.org\/10.64898\/2026.05.11.724358","relation":{},"subject":[],"published":{"date-parts":[[2026,5,14]]},"subtype":"preprint"}}