{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:56:29Z","timestamp":1791564989624,"version":"4.3.4"},"posted":{"date-parts":[[2026,10,1]]},"group-title":"Pathology","reference-count":87,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01AR072052"],"award-info":[{"award-number":["R01AR072052"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/0142eak56","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Individuals with fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder caused by mutations in the bone morphogenetic protein receptor ACVR1 (also known as ALK2), experience progressive and severely debilitating endochondral heterotopic ossification (HO). Previous studies have identified fibro-adipogenic progenitors (FAPs) as a major cellular source of HO in FOP mouse models. Here, we used mRNA sequencing of FAPs isolated from injured muscle of FOP mice to capture the earliest gene expression changes associated with the transformation of muscle tissues into bone. Whereas the transcriptomes of mutant and wild-type FAPs were indistinguishable prior to injury and at 1 day post injury, dramatic dysregulation of gene expression was observed at 3 and 5 days after injury. Surprisingly, gene expression changes suggested early specification of osteochondral lineages by 3 days post injury, approximately 3 to 4 days before the appearance of histologically identifiable cartilage. We identified dysregulation of genes encoding components of major signaling pathways, cell cycle regulators, extracellular matrix components, and hypoxia response mediators, and showed that these gene expression changes are temporally associated with abnormal population growth of mutant FAPs. We further demonstrated that treatment of FOP mice with either an anti-activin A monoclonal antibody or the ACVR1 kinase inhibitor BLU-782 (IPN60130; fidrisertib) normalized the expression of the majority of dysregulated FAP genes. However, the relative efficacy of the drugs differed, and distinct sets of overlapping genes were normalized by the treatments. The substantial transcriptional changes caused by these drugs in FAPs from normally regenerating muscle were also enumerated and described. These findings define early transcriptional events associated with pathogenic FAP reprogramming and provide a molecular framework for understanding the shared and distinct effects of activin A and ACVR1 inhibition.<\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Early transcriptional reprogramming of fibro-adipogenic progenitors in FOP mice<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.23.752902","type":"posted-content","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:56:28Z","timestamp":1790866588000},"source":"Crossref","is-referenced-by-count":0,"title":["Pathogenic transcriptional reprogramming of fibro-adipogenic progenitors in mice with FOP and its mitigation by inhibition of ACVR1 and activin A"],"prefix":"10.64898","author":[{"given":"Sean J.","family":"Stoessel","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269"},{"name":"Alexion Pharmaceuticals, New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine N.","family":"Burdick","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269"},{"name":"TBP Diagnostics, Storrs, CT 06269"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison J.","family":"Davis","sequence":"additional","affiliation":[{"name":"Blueprint Medicines, Cambridge, MA 02139"},{"name":"Dunad Therapeutics, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-8921","authenticated-orcid":false,"given":"David J.","family":"Goldhamer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"5","key":"2026100909250956000_2026.09.23.752902v1.1","doi-asserted-by":"crossref","first-page":"R1173","DOI":"10.1152\/ajpregu.00735.2009","article-title":"Regulatory interactions between muscle and the immune system during muscle regeneration. Am. J. Physiol.-Regul","volume":"298","year":"2010","journal-title":"Integr. Comp. Physiol"},{"key":"2026100909250956000_2026.09.23.752902v1.2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00019.2003"},{"key":"2026100909250956000_2026.09.23.752902v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.06.018"},{"key":"2026100909250956000_2026.09.23.752902v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2015"},{"key":"2026100909250956000_2026.09.23.752902v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2014"},{"issue":"4","key":"2026100909250956000_2026.09.23.752902v1.6","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/emmm.201202096","article-title":"Fibroadipogenic progenitors mediate the ability of HDAC inhibitors to promote regeneration in dystrophic muscles of young, but not old Mdx mice","volume":"5","year":"2013","journal-title":"EMBO molecular medicine"},{"key":"2026100909250956000_2026.09.23.752902v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2016.06.007"},{"key":"2026100909250956000_2026.09.23.752902v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.053"},{"key":"2026100909250956000_2026.09.23.752902v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3869"},{"key":"2026100909250956000_2026.09.23.752902v1.10","doi-asserted-by":"crossref","first-page":"103020","DOI":"10.1016\/j.ebiom.2020.103020","article-title":"Retinoic acid signalling in fibro\/adipogenic progenitors robustly enhances muscle regeneration","volume":"60","year":"2020","journal-title":"Ebiomedicine"},{"key":"2026100909250956000_2026.09.23.752902v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.04.074"},{"key":"2026100909250956000_2026.09.23.752902v1.12","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1562"},{"key":"2026100909250956000_2026.09.23.752902v1.13","doi-asserted-by":"publisher","DOI":"10.1101\/gad.234468.113"},{"key":"2026100909250956000_2026.09.23.752902v1.14","doi-asserted-by":"crossref","first-page":"101277","DOI":"10.1016\/j.mam.2024.101277","article-title":"Fibro-adipogenic progenitors in physiological adipogenesis and intermuscular adipose tissue remodeling","volume":"97","year":"2024","journal-title":"Mol. Asp. Med"},{"key":"2026100909250956000_2026.09.23.752902v1.15","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.H.01177"},{"issue":"3","key":"2026100909250956000_2026.09.23.752902v1.16","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.gendis.2022.09.002","article-title":"Myelin protein zero (P0)- and Wnt1-Cre marked muscle resident neural crest-derived mesenchymal progenitor cells give rise to heterotopic ossification in mouse models","volume":"10","year":"2023","journal-title":"Genes Dis"},{"key":"2026100909250956000_2026.09.23.752902v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4020"},{"key":"2026100909250956000_2026.09.23.752902v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.122"},{"key":"2026100909250956000_2026.09.23.752902v1.19","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2728"},{"key":"2026100909250956000_2026.09.23.752902v1.20","doi-asserted-by":"publisher","DOI":"10.1080\/16501970510027628"},{"issue":"3","key":"2026100909250956000_2026.09.23.752902v1.21","first-page":"686","article-title":"Early mortality and cardiorespiratory failure in patients with fibrodysplasia ossificans progressiva","volume":"92","year":"2010","journal-title":"The Journal of bone and joint surgery. American volume"},{"key":"2026100909250956000_2026.09.23.752902v1.22","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.0106"},{"key":"2026100909250956000_2026.09.23.752902v1.23","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21730"},{"key":"2026100909250956000_2026.09.23.752902v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-02872-2"},{"issue":"12","key":"2026100909250956000_2026.09.23.752902v1.25","doi-asserted-by":"crossref","first-page":"e153795","DOI":"10.1172\/JCI153795","article-title":"An anti-ACVR1 antibody exacerbates heterotopic ossification by fibro-adipogenic progenitors in fibrodysplasia ossificans progressiva mice","volume":"132","year":"2022","journal-title":"J Clin Invest"},{"issue":"11","key":"2026100909250956000_2026.09.23.752902v1.26","first-page":"2077","article-title":"Overexpression of Wild-Type ACVR1 in Fibrodysplasia Ossificans Progressiva Mice Rescues Perinatal Lethality and Inhibits Heterotopic Ossification","volume":"37","year":"2022","journal-title":"J Bone Miner Res"},{"key":"2026100909250956000_2026.09.23.752902v1.27","first-page":"305","article-title":"Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity","volume":"7","year":"2018","journal-title":"eLife"},{"key":"2026100909250956000_2026.09.23.752902v1.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1510540112"},{"key":"2026100909250956000_2026.09.23.752902v1.29","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac4358"},{"key":"2026100909250956000_2026.09.23.752902v1.30","doi-asserted-by":"crossref","unstructured":"Davis AJ , Brooijmans N , Brubaker JD , Stevison F , LaBranche TP , Albayya F , Fleming P , Hodous BL , Kim JL , Kim S , Lobbardi R , Palmer M , Sheets MP , Vassiliadis J , Wang R , Williams BD , Wilson D , Xu L , Zhu XJ , Bouchard K , Hunter JW , Graul C , Greenblatt E , Hussein A , Lyon M , Russo J , Stewart R , Dorsch M , Guzi TJ , Kadambi V , Lengauer C , Garner AP . An ALK2 inhibitor, BLU-782, prevents heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva. Sci. Transl. Med. 2024;16(749).","DOI":"10.1126\/scitranslmed.abp8334"},{"issue":"2","key":"2026100909250956000_2026.09.23.752902v1.31","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3390\/biom14020177","article-title":"Sex as a Critical Variable in Basic and Pre-Clinical Studies of Fibrodysplasia Ossificans Progressiva","volume":"14","year":"2024","journal-title":"Biomolecules"},{"key":"2026100909250956000_2026.09.23.752902v1.32","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656."},{"key":"2026100909250956000_2026.09.23.752902v1.33","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"issue":"20","key":"2026100909250956000_2026.09.23.752902v1.34","first-page":"2678","article-title":"Qualimap: evaluating next-generation sequencing alignment data","volume":"28","year":"2012","journal-title":"Bioinform. (Oxf., Engl.)"},{"key":"2026100909250956000_2026.09.23.752902v1.35","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026100909250956000_2026.09.23.752902v1.36","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1038"},{"key":"2026100909250956000_2026.09.23.752902v1.37","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformabcs\/btz931"},{"key":"2026100909250956000_2026.09.23.752902v1.38","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20474"},{"key":"2026100909250956000_2026.09.23.752902v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2019.07.008"},{"issue":"3","key":"2026100909250956000_2026.09.23.752902v1.40","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/stem.2515","article-title":"Scleraxis-Lineage Cells Contribute to Ectopic Bone Formation in Muscle and Tendon","volume":"35","year":"2017","journal-title":"Stem Cells"},{"issue":"2","key":"2026100909250956000_2026.09.23.752902v1.41","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.gendis.2014.09.004","article-title":"The versatile functions of Sox9 in development, stem cells, and human diseases","volume":"1","year":"2014","journal-title":"Genes Dis"},{"issue":"1","key":"2026100909250956000_2026.09.23.752902v1.42","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41413-019-0064-9","article-title":"Conditional disruption of the osterix gene in chondrocytes during early postnatal growth impairs secondary ossification in the mouse tibial epiphysis","volume":"7","year":"2019","journal-title":"Bone Res"},{"key":"2026100909250956000_2026.09.23.752902v1.43","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.337063"},{"key":"2026100909250956000_2026.09.23.752902v1.44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.12.8695"},{"key":"2026100909250956000_2026.09.23.752902v1.45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906266106"},{"issue":"1","key":"2026100909250956000_2026.09.23.752902v1.46","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1387\/ijdb.9074941","article-title":"Differential effects of transforming growth factors beta 1, beta 2, beta 3 and beta 5 on chondrogenesis in mouse limb bud mesenchymal cells","volume":"41","year":"1997","journal-title":"Int. J. Dev. Biol"},{"key":"2026100909250956000_2026.09.23.752902v1.47","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-02988-5"},{"issue":"10","key":"2026100909250956000_2026.09.23.752902v1.48","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1038\/s41418-020-0551-y","article-title":"Adipogenesis of skeletal muscle fibro\/adipogenic progenitors is affected by the WNT5a\/GSK3\/\u03b2-catenin axis","volume":"27","year":"2020","journal-title":"Cell Death Differ"},{"key":"2026100909250956000_2026.09.23.752902v1.49","doi-asserted-by":"crossref","first-page":"627429","DOI":"10.3389\/fcell.2021.627429","article-title":"Running Against the Wnt: How Wnt\/\u03b2-Catenin Suppresses Adipogenesis","volume":"9","year":"2021","journal-title":"Frontiers Cell Dev Biology"},{"key":"2026100909250956000_2026.09.23.752902v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELREP.2019.07.023"},{"key":"2026100909250956000_2026.09.23.752902v1.51","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200303158"},{"key":"2026100909250956000_2026.09.23.752902v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(80)90517-0"},{"key":"2026100909250956000_2026.09.23.752902v1.53","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200112029"},{"issue":"2","key":"2026100909250956000_2026.09.23.752902v1.54","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/jor.20985","article-title":"Inhibition of ectopic bone formation by a selective retinoic acid receptor alpha-agonist: a new therapy for heterotopic ossification?","volume":"28","year":"2010","journal-title":"J Ortho Res"},{"key":"2026100909250956000_2026.09.23.752902v1.55","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2820"},{"key":"2026100909250956000_2026.09.23.752902v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2334"},{"key":"2026100909250956000_2026.09.23.752902v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3932"},{"key":"2026100909250956000_2026.09.23.752902v1.58","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1998.9176"},{"issue":"1","key":"2026100909250956000_2026.09.23.752902v1.59","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41536-021-00201-8","article-title":"Dynamics of skeletal muscle-resident stem cells during myogenesis in fibrodysplasia ossificans progressiva","volume":"7","year":"2022","journal-title":"NPJ Regen Med"},{"key":"2026100909250956000_2026.09.23.752902v1.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.11.004"},{"key":"2026100909250956000_2026.09.23.752902v1.61","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2016"},{"key":"2026100909250956000_2026.09.23.752902v1.62","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515397113"},{"key":"2026100909250956000_2026.09.23.752902v1.63","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2848"},{"issue":"1","key":"2026100909250956000_2026.09.23.752902v1.64","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3390\/cells11010038","article-title":"Molecular Mechanisms and Regulation of Mammalian Mitophagy","volume":"11","year":"2021","journal-title":"Cells"},{"key":"2026100909250956000_2026.09.23.752902v1.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.06.148"},{"key":"2026100909250956000_2026.09.23.752902v1.66","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3292"},{"key":"2026100909250956000_2026.09.23.752902v1.67","doi-asserted-by":"publisher","DOI":"10.1101\/gad.934301"},{"key":"2026100909250956000_2026.09.23.752902v1.68","doi-asserted-by":"publisher","DOI":"10.1242\/dev.008441"},{"issue":"2","key":"2026100909250956000_2026.09.23.752902v1.69","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.stemcr.2016.07.003","article-title":"MIF Plays a Key Role in Regulating Tissue-Specific Chondro-Osteogenic Differentiation Fate of Human Cartilage Endplate Stem Cells under Hypoxia","volume":"7","year":"2016","journal-title":"Stem Cell Rep"},{"key":"2026100909250956000_2026.09.23.752902v1.70","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707729200"},{"key":"2026100909250956000_2026.09.23.752902v1.71","doi-asserted-by":"publisher","DOI":"10.1002\/mus.22094"},{"key":"2026100909250956000_2026.09.23.752902v1.72","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20170719"},{"key":"2026100909250956000_2026.09.23.752902v1.73","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.14.2553"},{"key":"2026100909250956000_2026.09.23.752902v1.74","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01074"},{"key":"2026100909250956000_2026.09.23.752902v1.75","doi-asserted-by":"crossref","unstructured":"Fukada S , Uezumi A . Roles and heterogeneity of mesenchymal progenitors in muscle homeostasis, hypertrophy, and disease. Stem Cells. 2023;","DOI":"10.1093\/stmcls\/sxad023"},{"issue":"10","key":"2026100909250956000_2026.09.23.752902v1.76","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1016\/j.celrep.2020.02.067","article-title":"Single-Cell Analysis of the Muscle Stem Cell Hierarchy Identifies Heterotypic Communication Signals Involved in Skeletal Muscle Regeneration","volume":"30","year":"2020","journal-title":"Cell Reports"},{"key":"2026100909250956000_2026.09.23.752902v1.77","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300250"},{"key":"2026100909250956000_2026.09.23.752902v1.78","doi-asserted-by":"crossref","first-page":"117829","DOI":"10.1016\/j.bone.2026.117829","article-title":"The role of muscle fascia in heterotopic ossification and maintenance of skeletal muscle integrity in fibrodysplasia ossificans progressiva","volume":"207","year":"2026","journal-title":"Bone"},{"key":"2026100909250956000_2026.09.23.752902v1.79","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.086629"},{"issue":"2","key":"2026100909250956000_2026.09.23.752902v1.80","first-page":"437","article-title":"Elevated BMP and Mechanical Signaling Through YAP1\/RhoA Poises FOP Mesenchymal Progenitors for Osteogenesis","volume":"10","year":"2019","journal-title":"J Bone Miner Res"},{"key":"2026100909250956000_2026.09.23.752902v1.81","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33956-9"},{"issue":"4","key":"2026100909250956000_2026.09.23.752902v1.82","doi-asserted-by":"crossref","first-page":"100993","DOI":"10.1016\/j.isci.2020.100993","article-title":"Temporal Dynamics and Heterogeneity of Cell Populations during Skeletal Muscle Regeneration","volume":"23","year":"2020","journal-title":"Iscience"},{"issue":"1","key":"2026100909250956000_2026.09.23.752902v1.83","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/s42003-021-02810-x","article-title":"Large-scale integration of single-cell transcriptomic data captures transitional progenitor states in mouse skeletal muscle regeneration","volume":"4","year":"2021","journal-title":"Commun Biology"},{"issue":"4","key":"2026100909250956000_2026.09.23.752902v1.84","doi-asserted-by":"crossref","first-page":"102372","DOI":"10.1016\/j.isci.2021.102372","article-title":"Early satellite cell communication creates a permissive environment for long-term muscle growth","volume":"24","year":"2021","journal-title":"iScience"},{"key":"2026100909250956000_2026.09.23.752902v1.85","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21446"},{"key":"2026100909250956000_2026.09.23.752902v1.86","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4827(05)80067-9"},{"key":"2026100909250956000_2026.09.23.752902v1.87","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02561-8"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.23.752902","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:25:23Z","timestamp":1791563123000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.23.752902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":87,"URL":"https:\/\/doi.org\/10.64898\/2026.09.23.752902","relation":{},"subject":[],"published":{"date-parts":[[2026,10,1]]},"subtype":"preprint"}}