{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:36:01Z","timestamp":1785404161877,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,22]]},"group-title":"Synthetic Biology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["CGCATF-2021\/100002"],"award-info":[{"award-number":["CGCATF-2021\/100002"]}],"id":[{"id":"https:\/\/ror.org\/054225q67","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["CA278687-01"],"award-info":[{"award-number":["CA278687-01"]}]},{"name":"National Cancer Institute","award":["R35CA220500"],"award-info":[{"award-number":["R35CA220500"]}]},{"name":"National Cancer Institute","award":["5T32CA009140-50"],"award-info":[{"award-number":["5T32CA009140-50"]}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["7R35GM125034"],"award-info":[{"award-number":["7R35GM125034"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R01GM147893"],"award-info":[{"award-number":["R01GM147893"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"award":["ACS134055-IRG-218"],"award-info":[{"award-number":["ACS134055-IRG-218"]}],"id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014599","name":"The Mark Foundation for Cancer Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014599","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Lindonlight Collective"},{"name":"NIH","award":["CA016520"],"award-info":[{"award-number":["CA016520"]}]},{"name":"NIH","award":["AI045008"],"award-info":[{"award-number":["AI045008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  T cell receptors (TCRs) and TCR-mimicking antibodies recognize peptide antigens in the context of specific Human Leucocyte Antigen (HLA-I) allotypes, and the extreme polymorphism of the HLA locus limits the breadth of immunotherapy development. Key barriers include divergent molecular surfaces on HLA proteins and differences in the peptide structure. As a result, existing modalities cannot confer therapeutic coverage across patients of divergent genetic backgrounds. Here, we develop an approach which combines a peptide conformational prediction tool, PepPred, with a cross-HLA binding protein engineering system, TRACeR-I\n                  <jats:sup>1<\/jats:sup>\n                  , to outline a generalized framework for developing binders (xTRACeRs) with compatibility across HLA allotypes while maintaining high levels of specificity towards the peptide antigen. We use our system to develop and validate xTRACeRs against clinically relevant, established peptide antigens presented across common alleles within five HLA-A\/B\/C supertypes\n                  <jats:sup>2<\/jats:sup>\n                  . Cryo-EM structures of xTRACeR-pHLA complexes for an oncofetal antigen from\n                  <jats:italic>PRAME<\/jats:italic>\n                  and a neuroblastoma-specific peptide from\n                  <jats:italic>PHOX2B<\/jats:italic>\n                  reveal effective mechanisms to navigate polymorphic HLA surface residues, and extensive interactions with the peptide. We implemented these two xTRACeRs as Chimeric Antigen Receptor (CAR) T cells and demonstrated their potent killing efficacy and specificity. Overcoming restriction across HLA supertypes lifts a key barrier in HLA-targeted immunotherapy by expanding patient coverage.\n                <\/jats:p>","DOI":"10.64898\/2026.05.21.726655","type":"posted-content","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T04:30:16Z","timestamp":1779510616000},"source":"Crossref","is-referenced-by-count":0,"title":["A generalizable system for antigenic peptide targeting across HLA-I allotypes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2452-5915","authenticated-orcid":false,"given":"Wyatt","family":"Blackson","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ean L.","family":"Small","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6764-5750","authenticated-orcid":false,"given":"Shirley M.","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"},{"name":"Cancer Biology Graduate Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omkar","family":"Shinde","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"},{"name":"Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Pantula","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0379-4788","authenticated-orcid":false,"given":"Sean J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2985-9954","authenticated-orcid":false,"given":"Photis","family":"Rotsides","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"},{"name":"Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"},{"name":"Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6071-8271","authenticated-orcid":false,"given":"Daniel","family":"Hwang","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"},{"name":"Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe S.","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"},{"name":"Immunology Graduate Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3365-1542","authenticated-orcid":false,"given":"Tianyu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Laskawy","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4183-1332","authenticated-orcid":false,"given":"Richa","family":"Kapoor","sequence":"additional","affiliation":[{"name":"Division of Oncology and Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9675-8910","authenticated-orcid":false,"given":"Muzamil Y.","family":"Want","sequence":"additional","affiliation":[{"name":"Division of Oncology and Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0241-3557","authenticated-orcid":false,"given":"Carl H.","family":"June","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies of the University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-9449","authenticated-orcid":false,"given":"Regina M.","family":"Young","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies of the University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8088-7929","authenticated-orcid":false,"given":"John M.","family":"Maris","sequence":"additional","affiliation":[{"name":"Division of Oncology and Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7948-2895","authenticated-orcid":false,"given":"Po-Ssu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3655-3902","authenticated-orcid":false,"given":"Nikolaos G.","family":"Sgourakis","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"},{"name":"Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Department of Bioengineering, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052609500698000_2026.05.21.726655v1.1","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1038\/s41587-024-02505-8","article-title":"Targeting peptide antigens using a multiallelic MHC I-binding system","volume":"43","year":"2025","journal-title":"Nat. Biotechnol"},{"key":"2026052609500698000_2026.05.21.726655v1.2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-9-1"},{"key":"2026052609500698000_2026.05.21.726655v1.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2005.00316.x"},{"key":"2026052609500698000_2026.05.21.726655v1.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa4971"},{"key":"2026052609500698000_2026.05.21.726655v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2025.11.007"},{"key":"2026052609500698000_2026.05.21.726655v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13233"},{"key":"2026052609500698000_2026.05.21.726655v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf1218"},{"key":"2026052609500698000_2026.05.21.726655v1.8","first-page":"487","article-title":"Targeting public neoantigens for cancer immunotherapy. Nat","volume":"2","year":"2021","journal-title":"Cancer"},{"key":"2026052609500698000_2026.05.21.726655v1.9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.59.070190.001345"},{"key":"2026052609500698000_2026.05.21.726655v1.10","doi-asserted-by":"crossref","first-page":"e2518820123","DOI":"10.1073\/pnas.2518820123","article-title":"Computational design of HLA class I superbinders for broad T cell immunogenicity","volume":"123","year":"2026","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"2026052609500698000_2026.05.21.726655v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2025.06.011"},{"key":"2026052609500698000_2026.05.21.726655v1.12","doi-asserted-by":"crossref","first-page":"6349","DOI":"10.1038\/s41467-023-42163-z","article-title":"HLA3DB: comprehensive annotation of peptide\/HLA complexes enables blind structure prediction of T cell epitopes","volume":"14","year":"2023","journal-title":"Nat. Commun"},{"key":"2026052609500698000_2026.05.21.726655v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.10.030"},{"key":"2026052609500698000_2026.05.21.726655v1.14","doi-asserted-by":"crossref","first-page":"8204","DOI":"10.1038\/s41467-023-43654-9","article-title":"Conformational plasticity of RAS Q61 family of neoepitopes results in distinct features for targeted recognition","volume":"14","year":"2023","journal-title":"Nat. Commun"},{"key":"2026052609500698000_2026.05.21.726655v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/S41586-021-03819-2"},{"key":"2026052609500698000_2026.05.21.726655v1.16","doi-asserted-by":"publisher","DOI":"10.1101\/2025.08.18.670959"},{"key":"2026052609500698000_2026.05.21.726655v1.17","doi-asserted-by":"crossref","first-page":"1616113","DOI":"10.3389\/fimmu.2025.1616113","article-title":"NetMHCpan-4.2: improved prediction of CD8+ epitopes by use of transfer learning and structural features","volume":"16","year":"2025","journal-title":"Front. Immunol"},{"key":"2026052609500698000_2026.05.21.726655v1.18","doi-asserted-by":"crossref","first-page":"26851","DOI":"10.1038\/s41598-024-75140-7","article-title":"Broadening alloselectivity of T cell receptors by structure guided engineering","volume":"14","year":"2024","journal-title":"Sci. Rep"},{"key":"2026052609500698000_2026.05.21.726655v1.19","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1038\/s41591-025-03650-6","article-title":"Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial","volume":"31","year":"2025","journal-title":"Nat. Med"},{"key":"2026052609500698000_2026.05.21.726655v1.20","doi-asserted-by":"crossref","first-page":"e15702","DOI":"10.1111\/tan.15702","article-title":"A new strategy for systematically classifying HLA alleles into serological specificities: Update and refinement","volume":"104","year":"2024","journal-title":"HLA"},{"key":"2026052609500698000_2026.05.21.726655v1.21","doi-asserted-by":"publisher","DOI":"10.1086\/424530"},{"key":"2026052609500698000_2026.05.21.726655v1.22","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adj5792"},{"key":"2026052609500698000_2026.05.21.726655v1.23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1032403"},{"key":"2026052609500698000_2026.05.21.726655v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24562-2"},{"key":"2026052609500698000_2026.05.21.726655v1.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1921964117"},{"key":"2026052609500698000_2026.05.21.726655v1.26","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1007\/s11427-020-1888-1","article-title":"Rational discovery of a cancer neoepitope harboring the KRAS G12D driver mutation","volume":"64","year":"2021","journal-title":"Sci. China Life Sci"},{"key":"2026052609500698000_2026.05.21.726655v1.27","doi-asserted-by":"crossref","first-page":"e75670","DOI":"10.7554\/eLife.75670","article-title":"T cells discriminate between groups C1 and C2 HLA-C","volume":"11","year":"2022","journal-title":"eLife"},{"key":"2026052609500698000_2026.05.21.726655v1.28","first-page":"1557","article-title":"LRRC15-CAR T Cells for the Treatment of Osteosarcoma","volume":"32","year":"2026","journal-title":"Cli. Cancer Res. Off. J. Am. Assoc. Cancer Res"},{"key":"2026052609500698000_2026.05.21.726655v1.29","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1074\/mcp.RA119.001617","article-title":"Identification of an Unconventional Subpeptidome Bound to the Beh\u00e7et\u2019s Disease-associated HLA-B*51:01 that is Regulated by Endoplasmic Reticulum Aminopeptidase 1 (ERAP1)","volume":"19","year":"2020","journal-title":"Mol. Cell. Proteomics MCP"},{"key":"2026052609500698000_2026.05.21.726655v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.02.007"},{"key":"2026052609500698000_2026.05.21.726655v1.31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.7.4910"},{"key":"2026052609500698000_2026.05.21.726655v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06706-0"},{"key":"2026052609500698000_2026.05.21.726655v1.33","doi-asserted-by":"crossref","first-page":"eaeb0821","DOI":"10.1126\/sciadv.aeb0821","article-title":"HLA-Shuttle: A system for enhancing antigen presentation in immunologically cold tumors","volume":"12","year":"2026","journal-title":"Sci. Adv"},{"key":"2026052609500698000_2026.05.21.726655v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15924"},{"key":"2026052609500698000_2026.05.21.726655v1.35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1170462"},{"key":"2026052609500698000_2026.05.21.726655v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15710-1"},{"key":"2026052609500698000_2026.05.21.726655v1.37","first-page":"1","article-title":"High-Throughput Production of Class I MHC Tetramers for Immunological Studies Using Chaperone-Mediated Peptide Exchange","volume":"3007","year":"2026","journal-title":"Methods Mol. Biol"},{"key":"2026052609500698000_2026.05.21.726655v1.38","doi-asserted-by":"crossref","first-page":"D451","DOI":"10.1093\/nar\/gkaf1188","article-title":"The PROSITE database for protein families, domains, and sites","volume":"54","year":"2026","journal-title":"Nucleic Acids Res"},{"key":"2026052609500698000_2026.05.21.726655v1.39","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1092"},{"key":"2026052609500698000_2026.05.21.726655v1.40","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1021\/acs.jproteome.2c00498","article-title":"The 2022 Report on the Human Proteome from the HUPO Human Proteome Project","volume":"22","year":"2023","journal-title":"J. Proteome Res"},{"key":"2026052609500698000_2026.05.21.726655v1.41","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-011366"},{"key":"2026052609500698000_2026.05.21.726655v1.42","doi-asserted-by":"crossref","first-page":"e175790","DOI":"10.1172\/JCI175790","article-title":"Natural TCRs targeting KRASG12V display fine specificity and sensitivity to human solid tumors","volume":"134","year":"2024","journal-title":"J. Clin. Invest"},{"key":"2026052609500698000_2026.05.21.726655v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0051-2"},{"key":"2026052609500698000_2026.05.21.726655v1.44","first-page":"5","article-title":"Swiss army knife T cell: one T cell many tumor targets","volume":"34","year":"2024","journal-title":"Cell Res"},{"key":"2026052609500698000_2026.05.21.726655v1.45","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1016\/j.ymthe.2025.03.005","article-title":"From concept to cure: The evolution of CAR-T cell therapy","volume":"33","year":"2025","journal-title":"Mol. Ther"},{"key":"2026052609500698000_2026.05.21.726655v1.46","doi-asserted-by":"publisher","DOI":"10.1172\/JCI92335"},{"key":"2026052609500698000_2026.05.21.726655v1.47","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-03-490565"},{"key":"2026052609500698000_2026.05.21.726655v1.48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2216697120"},{"key":"2026052609500698000_2026.05.21.726655v1.49","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz1776"},{"key":"2026052609500698000_2026.05.21.726655v1.50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2311500121"},{"key":"2026052609500698000_2026.05.21.726655v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2013.06.025"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.21.726655","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T16:50:19Z","timestamp":1779814219000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.21.726655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":51,"URL":"https:\/\/doi.org\/10.64898\/2026.05.21.726655","relation":{},"subject":[],"published":{"date-parts":[[2026,5,22]]},"subtype":"preprint"}}