{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:16:55Z","timestamp":1785421015941,"version":"3.56.0"},"posted":{"date-parts":[[2025,5,15]]},"group-title":"Cancer Biology","reference-count":93,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Lombardi Comprehensive Cancer Center, Washington, DC"},{"name":"Sylvester Comprehensive Cancer Center, Miami, FL"},{"award":["P30CA240139"],"award-info":[{"award-number":["P30CA240139"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["RM1NS133003"],"award-info":[{"award-number":["RM1NS133003"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Bellringer"},{"name":"NSF ACCESS","award":["BIO240140"],"award-info":[{"award-number":["BIO240140"]}]},{"name":"NSF ACCESS","award":["2138259"],"award-info":[{"award-number":["2138259"]}]},{"name":"NSF ACCESS","award":["2138286"],"award-info":[{"award-number":["2138286"]}]},{"name":"NSF ACCESS","award":["2138307"],"award-info":[{"award-number":["2138307"]}]},{"name":"NSF ACCESS","award":["2137603"],"award-info":[{"award-number":["2137603"]}]},{"name":"NSF ACCESS","award":["2138296"],"award-info":[{"award-number":["2138296"]}]},{"name":"American Cancer Society Institutional Research Grant","award":["IRG-23-1156148-27-IRG"],"award-info":[{"award-number":["IRG-23-1156148-27-IRG"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Glioblastoma (GBM) remains the most common and lethal adult malignant primary brain cancer with few treatment options. A significant issue hindering GBM therapeutic development is intratumor heterogeneity. GBM tumors contain neoplastic cells within a spectrum of different transcriptional states. Identifying effective therapeutics requires a platform that predicts the differential sensitivity and resistance of these states to various treatments. Here, we developed a novel framework, ISOSCELES (\n                  <jats:underline>I<\/jats:underline>\n                  nferred cell\n                  <jats:underline>S<\/jats:underline>\n                  ensitivity\n                  <jats:underline>O<\/jats:underline>\n                  perating on the integration of\n                  <jats:underline>S<\/jats:underline>\n                  ingle-\n                  <jats:underline>C<\/jats:underline>\n                  ell\n                  <jats:underline>E<\/jats:underline>\n                  xpression and\n                  <jats:underline>L<\/jats:underline>\n                  1000\n                  <jats:underline>E<\/jats:underline>\n                  xpression\n                  <jats:underline>S<\/jats:underline>\n                  ignatures), to quantify the cellular drug sensitivity and resistance landscape. Using single-cell RNA sequencing of newly diagnosed and recurrent GBM tumors, we identified compounds from the LINCS L1000 database with transcriptional response signatures selectively discordant with distinct GBM cell states. We validated the significance of these findings\n                  <jats:italic>in vitro, ex vivo,<\/jats:italic>\n                  and\n                  <jats:italic>in vivo<\/jats:italic>\n                  , and identified a novel combination of an OLIG2 inhibitor and Depatux-M for GBM. Our studies suggest that ISOSCELES identifies cell states sensitive and resistant to targeted therapies in GBM and that it can be applied to identify new synergistic combinations.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Integration of GBM single-cell RNA sequencing data with L1000-derived drug response signatures facilitates clustering of tumor cells and small molecules on cell-drug connectivity.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Cell-drug connectivity predicts the identities of drug-sensitive and resistant cell states.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>In silico perturbation analysis using cell-drug connectivity predicts drug-induced changes in the cell-drug connectivity landscape in vivo.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>In silico perturbation analysis to predict drug-induced changes in the tumor cell-drug connectivity landscape predicts drug combinations that synergize in vivo to extend survival.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.15.654044","type":"posted-content","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T22:05:13Z","timestamp":1747346713000},"source":"Crossref","is-referenced-by-count":1,"title":["Drug and Single-Cell Gene Expression Integration Identifies Sensitive and Resistant Glioblastoma Cell Populations"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3335-8426","authenticated-orcid":false,"given":"Robert K.","family":"Suter","sequence":"first","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3271-051X","authenticated-orcid":false,"given":"Anna M.","family":"Jermakowicz","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rithvik","family":"Veeramachaneni","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1837-7004","authenticated-orcid":false,"given":"Matthew","family":"D\u2019Antuono","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1155-4171","authenticated-orcid":false,"given":"Longwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9090-5916","authenticated-orcid":false,"given":"Rishika","family":"Chowdary","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4449-6952","authenticated-orcid":false,"given":"Simon","family":"Kaeppeli","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Sharp","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4750-6537","authenticated-orcid":false,"given":"Pravallika","family":"Palwai","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1986-5947","authenticated-orcid":false,"given":"Vasileios","family":"Stathias","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, Institute for Data Science & Computing, University of Miami Miller School of Medicine, Miami, FL, USA"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6761-0899","authenticated-orcid":false,"given":"Luz","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winston","family":"Walters","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Cepero","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0014-5579","authenticated-orcid":false,"given":"Danielle","family":"Burgenske","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward B","family":"Reilly","sequence":"additional","affiliation":[{"name":"AbbVie, Oncology Discovery, North Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatol","family":"Oleksijew","sequence":"additional","affiliation":[{"name":"AbbVie, Oncology Discovery, North Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark G.","family":"Anderson","sequence":"additional","affiliation":[{"name":"AbbVie, Oncology Discovery, North Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-3455","authenticated-orcid":false,"given":"Sion Ll.","family":"Williams","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA"},{"name":"Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4798-4989","authenticated-orcid":false,"given":"Michael E.","family":"Ivan","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA"},{"name":"Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo J.","family":"Komotar","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA"},{"name":"Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena I.","family":"De La Fuente","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA"},{"name":"Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Stein","sequence":"additional","affiliation":[{"name":"Curtana Pharmaceuticals, Inc, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Wojcinski","sequence":"additional","affiliation":[{"name":"Pacific Neuroscience Institute and Saint John\u2019s Cancer Institute, Providence Health System, Santa Monica, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Kesari","sequence":"additional","affiliation":[{"name":"Pacific Neuroscience Institute and Saint John\u2019s Cancer Institute, Providence Health System, Santa Monica, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jann N.","family":"Sarkaria","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan C.","family":"Sch\u00fcrer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, Institute for Data Science & Computing, University of Miami Miller School of Medicine, Miami, FL, USA"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1994-3095","authenticated-orcid":false,"given":"Nagi G.","family":"Ayad","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041122083675000_2025.05.15.654044v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70025-7"},{"key":"2026041122083675000_2025.05.15.654044v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330"},{"key":"2026041122083675000_2025.05.15.654044v1.3","unstructured":"Tamimi, A. F. & Juweid, M. in Glioblastoma (ed S. De Vleeschouwer ) (2017)."},{"key":"2026041122083675000_2025.05.15.654044v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.03.007"},{"key":"2026041122083675000_2025.05.15.654044v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105060"},{"key":"2026041122083675000_2025.05.15.654044v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.024"},{"key":"2026041122083675000_2025.05.15.654044v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17186-5"},{"key":"2026041122083675000_2025.05.15.654044v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09853-z"},{"key":"2026041122083675000_2025.05.15.654044v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.01.006"},{"key":"2026041122083675000_2025.05.15.654044v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0156-x"},{"key":"2026041122083675000_2025.05.15.654044v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms16022"},{"key":"2026041122083675000_2025.05.15.654044v1.12","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdab192"},{"key":"2026041122083675000_2025.05.15.654044v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07659-z"},{"key":"2026041122083675000_2025.05.15.654044v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2017.11.001"},{"key":"2026041122083675000_2025.05.15.654044v1.15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-259523"},{"key":"2026041122083675000_2025.05.15.654044v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00926-8"},{"key":"2026041122083675000_2025.05.15.654044v1.17","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0249"},{"key":"2026041122083675000_2025.05.15.654044v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4306"},{"key":"2026041122083675000_2025.05.15.654044v1.19","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-016-2285-8"},{"key":"2026041122083675000_2025.05.15.654044v1.20","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.14.1"},{"key":"2026041122083675000_2025.05.15.654044v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25501-x"},{"key":"2026041122083675000_2025.05.15.654044v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2008.156"},{"key":"2026041122083675000_2025.05.15.654044v1.23","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12125"},{"key":"2026041122083675000_2025.05.15.654044v1.24","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-020-01895-x"},{"key":"2026041122083675000_2025.05.15.654044v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.08.022"},{"key":"2026041122083675000_2025.05.15.654044v1.26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900833106"},{"key":"2026041122083675000_2025.05.15.654044v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2018.12.007"},{"key":"2026041122083675000_2025.05.15.654044v1.28","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.5261"},{"key":"2026041122083675000_2025.05.15.654044v1.29","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.m112.021030"},{"key":"2026041122083675000_2025.05.15.654044v1.30","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2780-5"},{"key":"2026041122083675000_2025.05.15.654044v1.31","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-0089"},{"key":"2026041122083675000_2025.05.15.654044v1.32","doi-asserted-by":"publisher","DOI":"10.5507\/bp.2008.004"},{"key":"2026041122083675000_2025.05.15.654044v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0909-1053"},{"key":"2026041122083675000_2025.05.15.654044v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/srep30213"},{"key":"2026041122083675000_2025.05.15.654044v1.35","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000232"},{"key":"2026041122083675000_2025.05.15.654044v1.36","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.25.12.4977-4992.2005"},{"key":"2026041122083675000_2025.05.15.654044v1.37","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-1479"},{"key":"2026041122083675000_2025.05.15.654044v1.38","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201012061"},{"key":"2026041122083675000_2025.05.15.654044v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2022.128614"},{"key":"2026041122083675000_2025.05.15.654044v1.40","doi-asserted-by":"publisher","DOI":"10.1021\/ml500409n"},{"key":"2026041122083675000_2025.05.15.654044v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2018.12.019"},{"key":"2026041122083675000_2025.05.15.654044v1.42","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5664-11.2012"},{"key":"2026041122083675000_2025.05.15.654044v1.43","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2017.3880"},{"key":"2026041122083675000_2025.05.15.654044v1.44","doi-asserted-by":"publisher","DOI":"10.1186\/s13008-018-0040-6"},{"key":"2026041122083675000_2025.05.15.654044v1.45","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-016-0457-2"},{"key":"2026041122083675000_2025.05.15.654044v1.46","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.s74062"},{"key":"2026041122083675000_2025.05.15.654044v1.47","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01305-3"},{"key":"2026041122083675000_2025.05.15.654044v1.48","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-021-00894-y"},{"key":"2026041122083675000_2025.05.15.654044v1.49","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdad073"},{"key":"2026041122083675000_2025.05.15.654044v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54858-y"},{"key":"2026041122083675000_2025.05.15.654044v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54861-3"},{"key":"2026041122083675000_2025.05.15.654044v1.52","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-2949436\/v1"},{"key":"2026041122083675000_2025.05.15.654044v1.53","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1129434"},{"key":"2026041122083675000_2025.05.15.654044v1.54","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-22-0527"},{"key":"2026041122083675000_2025.05.15.654044v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-30376-y"},{"key":"2026041122083675000_2025.05.15.654044v1.56","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-009-9244-6"},{"key":"2026041122083675000_2025.05.15.654044v1.57","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-1342"},{"key":"2026041122083675000_2025.05.15.654044v1.58","doi-asserted-by":"publisher","DOI":"10.1358\/2006.42.4.968648"},{"key":"2026041122083675000_2025.05.15.654044v1.59","doi-asserted-by":"publisher","DOI":"10.1101\/2022.01.11.475728"},{"key":"2026041122083675000_2025.05.15.654044v1.60","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0209-6"},{"key":"2026041122083675000_2025.05.15.654044v1.61","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-022-00294-4"},{"key":"2026041122083675000_2025.05.15.654044v1.62","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254257"},{"key":"2026041122083675000_2025.05.15.654044v1.63","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03796-6"},{"key":"2026041122083675000_2025.05.15.654044v1.64","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13657-6"},{"key":"2026041122083675000_2025.05.15.654044v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1775-1"},{"key":"2026041122083675000_2025.05.15.654044v1.66","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noy020"},{"key":"2026041122083675000_2025.05.15.654044v1.67","doi-asserted-by":"publisher","DOI":"10.1101\/2021.05.03.442486"},{"key":"2026041122083675000_2025.05.15.654044v1.68","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54750-9"},{"key":"2026041122083675000_2025.05.15.654044v1.69","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.Can-23-4024"},{"key":"2026041122083675000_2025.05.15.654044v1.70","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab133"},{"key":"2026041122083675000_2025.05.15.654044v1.71","doi-asserted-by":"publisher","DOI":"10.1038\/npjsba.2016.15"},{"key":"2026041122083675000_2025.05.15.654044v1.72","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13817-8"},{"key":"2026041122083675000_2025.05.15.654044v1.73","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku476"},{"key":"2026041122083675000_2025.05.15.654044v1.74","doi-asserted-by":"publisher","DOI":"10.1172\/jci171136"},{"key":"2026041122083675000_2025.05.15.654044v1.75","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-02584-6"},{"key":"2026041122083675000_2025.05.15.654044v1.76","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0909"},{"key":"2026041122083675000_2025.05.15.654044v1.77","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.06-10-03044.1986"},{"key":"2026041122083675000_2025.05.15.654044v1.78","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"2026041122083675000_2025.05.15.654044v1.79","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"},{"key":"2026041122083675000_2025.05.15.654044v1.80","unstructured":"Hao, Y. et al. Integrated analysis of multimodal single-cell data (Cold Spring Harbor Laboratory, 2020)."},{"key":"2026041122083675000_2025.05.15.654044v1.81","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3192"},{"key":"2026041122083675000_2025.05.15.654044v1.82","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"2026041122083675000_2025.05.15.654044v1.83","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0844-5"},{"key":"2026041122083675000_2025.05.15.654044v1.84","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2435-4"},{"key":"2026041122083675000_2025.05.15.654044v1.85","unstructured":"pheatmap: Pretty Heatmaps v. 1.0.12 (2019)."},{"key":"2026041122083675000_2025.05.15.654044v1.86","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-60031-8"},{"key":"2026041122083675000_2025.05.15.654044v1.87","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2005970"},{"key":"2026041122083675000_2025.05.15.654044v1.88","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141"},{"key":"2026041122083675000_2025.05.15.654044v1.89","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01020-z"},{"key":"2026041122083675000_2025.05.15.654044v1.90","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2024.100722"},{"key":"2026041122083675000_2025.05.15.654044v1.91","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"2026041122083675000_2025.05.15.654044v1.92","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.049"},{"key":"2026041122083675000_2025.05.15.654044v1.93","unstructured":"_factoextra: Extract and Visualize the Results of Multivariate Data Analyses_. v. 1.0.7 (2020)."}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.05.15.654044","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:03:15Z","timestamp":1782277395000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.05.15.654044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":93,"URL":"https:\/\/doi.org\/10.1101\/2025.05.15.654044","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s41467-025-67783-5","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,5,15]]},"subtype":"preprint"}}