{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:24Z","timestamp":1792790364854,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,23]]},"group-title":"Cancer Biology","reference-count":74,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Bristol Myers Squibb"},{"id":[{"id":"https:\/\/ror.org\/01xsqw823","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Oxford Translational Myeloma Centre"},{"name":"Bone Cancer Research Trust","award":["BCRT11025"],"award-info":[{"award-number":["BCRT11025"]}],"id":[{"id":"https:\/\/ror.org\/02gsmy581","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Leducq Foundation","id":[{"id":"https:\/\/ror.org\/01czwga19","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Prostate Cancer UK","award":["RIA22-ST2-004"],"award-info":[{"award-number":["RIA22-ST2-004"]}],"id":[{"id":"https:\/\/ror.org\/04dkv6329","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Medical Research Council","award":["MR\/V010182\/1"],"award-info":[{"award-number":["MR\/V010182\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Multiple myeloma is a genetically complex plasma cell malignancy in which profound intra-tumoral heterogeneity shapes disease progression and therapeutic resistance. Genomic subclones dynamically emerge and evolve under treatment pressure, yet their spatial organization within intact bone marrow remains poorly defined. We hypothesized that genetically distinct myeloma subclones occupy spatially discrete ecological niches associated with unique molecular and microenvironmental states. To test this, we here demonstrate a proof-of-concept spatial tri-omics workflow combining laser capture microdissection-based genomics and deep LC-MS\/MS proteomics with single-cell spatial transcriptomics, integrated by digital co-registration of adjacent tissue sections. Applied to a myeloma bone marrow trephine, this approach enabled coordinated profiling of matched anatomical regions demonstrating that genomic, transcriptomic and proteomic profiles converged to define clone-specific microenvironmental programmes.<\/jats:p>\n                <jats:p>We show that genetically distinct myeloma subclones occupy mutually exclusive regions of the same bone marrow biopsy. Remarkably, an aggressive del(17p) clone and a gain(12q) clone occupied defined anatomical territories within the same trephine-biopsied section, each clone exhibiting distinct genomic, transcriptomic, proteomic and cellular ecosystems. The del(17p) clone localized to a fibrotic, osteolytic and angiogenic niche enriched for activated stromal cells, osteoblasts, osteoclasts and immunoregulatory myeloid populations, whereas the gain(12q) clone occupied a comparatively quiescent marrow niche with limited stromal remodelling. Together, these findings demonstrate that genetically distinct myeloma subclones establish spatially and biologically discrete ecological niches through coordinated remodelling of stromal, immune and bone compartments, providing a framework for understanding clonal evolution within the bone marrow microenvironment.<\/jats:p>","DOI":"10.64898\/2026.09.22.753531","type":"posted-content","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:00:18Z","timestamp":1790190018000},"source":"Crossref","is-referenced-by-count":0,"title":["A platform for deep topographic multiomic mapping of the bone marrow environment in multiple myeloma"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5239-5361","authenticated-orcid":false,"given":"Jinsen","family":"Lu","sequence":"first","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"},{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"},{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Davis","sequence":"additional","affiliation":[{"name":"Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund","family":"Watson","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"},{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"},{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Baker","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"},{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Calcutt","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"},{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Gooding","sequence":"additional","affiliation":[{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"},{"name":"Weatherall Institute of Molecular Medicine, University of Oxford,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7466-3849","authenticated-orcid":false,"given":"Joanna","family":"Hester","sequence":"additional","affiliation":[{"name":"Nuffield Department of Surgical Sciences, University of Oxford, University of Oxford,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8279-7732","authenticated-orcid":false,"given":"Fadi","family":"Issa","sequence":"additional","affiliation":[{"name":"Nuffield Department of Surgical Sciences, University of Oxford, University of Oxford,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Benevent","family":"Bellver","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Lagana","sequence":"additional","affiliation":[{"name":"Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, NY, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Bjorklund","sequence":"additional","affiliation":[{"name":"Translational Medicine, Bristol Myers Squibb, Summit, NJ, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3605-6394","authenticated-orcid":false,"given":"Giorgio","family":"Napolitani","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Stevenage, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-7787","authenticated-orcid":false,"given":"Sue","family":"Griffin","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Stevenage, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjan","family":"Thakurta","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"},{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3385-3707","authenticated-orcid":false,"given":"Karthik","family":"Ramasamy","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"},{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sozanska","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Laboratory Sciences, University of Oxford,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalin","family":"Cooper","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Laboratory Sciences, University of Oxford,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Royston","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Laboratory Sciences, University of Oxford,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Athanasou","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam P","family":"Cribbs","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"},{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Fischer","sequence":"additional","affiliation":[{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"},{"name":"Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9984-5342","authenticated-orcid":false,"given":"Udo","family":"Oppermann","sequence":"additional","affiliation":[{"name":"Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7LD, UK"},{"name":"Oxford Translational Myeloma Centre, University of Oxford, OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivasa","family":"Rao","sequence":"additional","affiliation":[{"name":"Nuffield Department of Surgical Sciences, University of Oxford, University of Oxford,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092603350883000_2026.09.22.753531v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05023-2"},{"key":"2026092603350883000_2026.09.22.753531v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.010"},{"key":"2026092603350883000_2026.09.22.753531v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-01038-7"},{"key":"2026092603350883000_2026.09.22.753531v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/J.MOLCEL.2022.05.022"},{"key":"2026092603350883000_2026.09.22.753531v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04217-4"},{"key":"2026092603350883000_2026.09.22.753531v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01203-6"},{"key":"2026092603350883000_2026.09.22.753531v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03634-9"},{"key":"2026092603350883000_2026.09.22.753531v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01937-y"},{"key":"2026092603350883000_2026.09.22.753531v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/S41587-021-00927-2"},{"key":"2026092603350883000_2026.09.22.753531v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0691-5"},{"key":"2026092603350883000_2026.09.22.753531v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4380"},{"key":"2026092603350883000_2026.09.22.753531v1.12","doi-asserted-by":"crossref","first-page":"17046","DOI":"10.1038\/nrdp.2017.46","article-title":"Multiple myeloma","volume":"3","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2026092603350883000_2026.09.22.753531v1.13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41572-024-00529-7","article-title":"Multiple myeloma","volume":"10","year":"2024","journal-title":"Nat Rev Dis Primers"},{"key":"2026092603350883000_2026.09.22.753531v1.14","doi-asserted-by":"crossref","first-page":"7040","DOI":"10.1038\/s41467-022-33944-z","article-title":"Single cell characterization of myeloma and its precursor conditions reveals transcriptional signatures of early tumorigenesis","volume":"13","year":"2022","journal-title":"Nat Commun"},{"key":"2026092603350883000_2026.09.22.753531v1.15","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.1038\/s41467-023-40584-4","article-title":"Resolving the spatial architecture of myeloma and its microenvironment at the single-cell level","volume":"14","year":"2023","journal-title":"Nat Commun"},{"key":"2026092603350883000_2026.09.22.753531v1.16","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12233"},{"key":"2026092603350883000_2026.09.22.753531v1.17","doi-asserted-by":"crossref","unstructured":"Merz, M. et al. Deciphering spatial genomic heterogeneity at a single cell resolution in multiple myeloma. Nat Commun 13, 807 (2022).","DOI":"10.1038\/s41467-022-28266-z"},{"key":"2026092603350883000_2026.09.22.753531v1.18","unstructured":"Soitu, C. et al. (bioRxiv, 2026)."},{"key":"2026092603350883000_2026.09.22.753531v1.19","doi-asserted-by":"crossref","first-page":"7710","DOI":"10.1038\/s41467-023-43520-8","article-title":"Deep topographic proteomics of a human brain tumour","volume":"14","year":"2023","journal-title":"Nat Commun"},{"key":"2026092603350883000_2026.09.22.753531v1.20","doi-asserted-by":"publisher","DOI":"10.1109\/34.24792"},{"key":"2026092603350883000_2026.09.22.753531v1.21","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-2095"},{"key":"2026092603350883000_2026.09.22.753531v1.22","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s00262-015-1694-4","article-title":"Optimal selection of natural killer cells to kill myeloma: the role of HLA-E and NKG2A","volume":"64","year":"2015","journal-title":"Cancer Immunol Immunother"},{"key":"2026092603350883000_2026.09.22.753531v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.06.002"},{"key":"2026092603350883000_2026.09.22.753531v1.24","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s43018-025-01072-4","article-title":"A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma","volume":"7","year":"2026","journal-title":"Nat Cancer"},{"key":"2026092603350883000_2026.09.22.753531v1.25","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1009"},{"key":"2026092603350883000_2026.09.22.753531v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.013"},{"key":"2026092603350883000_2026.09.22.753531v1.27","doi-asserted-by":"crossref","unstructured":"Huang, Y. & Fang, W . TREM2-mediated regulation of myeloid cells in the tumor microenvironment: new insights and therapeutic prospects. NPJ Precis Oncol 9, 359 (2025).","DOI":"10.1038\/s41698-025-01152-9"},{"key":"2026092603350883000_2026.09.22.753531v1.28","doi-asserted-by":"crossref","unstructured":"Robinson, M.H. et al. Regulation of antigen-specific T cell infiltration and spatial architecture in multiple myeloma and premalignancy. J Clin Invest 133 (2023).","DOI":"10.1172\/JCI167629"},{"key":"2026092603350883000_2026.09.22.753531v1.29","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1038\/s41467-024-47793-5","article-title":"Bone marrow stromal cells induce chromatin remodeling in multiple myeloma cells leading to transcriptional changes","volume":"15","year":"2024","journal-title":"Nat Commun"},{"key":"2026092603350883000_2026.09.22.753531v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00931-3"},{"key":"2026092603350883000_2026.09.22.753531v1.31","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s00262-017-1992-0","article-title":"Bone marrow myeloid cells in regulation of multiple myeloma progression","volume":"66","year":"2017","journal-title":"Cancer Immunol Immunother"},{"key":"2026092603350883000_2026.09.22.753531v1.32","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1038\/s42003-025-08975-z","article-title":"Characterization of the bone marrow architecture of multiple myeloma using spatial transcriptomics","volume":"8","year":"2025","journal-title":"Commun Biol"},{"key":"2026092603350883000_2026.09.22.753531v1.33","doi-asserted-by":"crossref","unstructured":"Ohlstrom, D.J. , et al. Spatial multi-omics of multiple myeloma uncovers niche-dependent pro-myeloma and immunosuppressive signaling in the bone marrow and extramedullary lesions. bioRxiv (2026).","DOI":"10.64898\/2026.03.23.713195"},{"key":"2026092603350883000_2026.09.22.753531v1.34","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1038\/s43018-024-00784-3","article-title":"The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities","volume":"5","year":"2024","journal-title":"Nat Cancer"},{"key":"2026092603350883000_2026.09.22.753531v1.35","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s43018-020-0053-3","article-title":"Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma","volume":"1","year":"2020","journal-title":"Nat Cancer"},{"key":"2026092603350883000_2026.09.22.753531v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/nature09837"},{"key":"2026092603350883000_2026.09.22.753531v1.37","doi-asserted-by":"crossref","first-page":"4517","DOI":"10.1038\/s41467-022-32145-y","article-title":"The spatio-temporal evolution of multiple myeloma from baseline to relapse-refractory states","volume":"13","year":"2022","journal-title":"Nat Commun"},{"key":"2026092603350883000_2026.09.22.753531v1.38","doi-asserted-by":"crossref","unstructured":"Koops, M. et al. Spatial profiling identifies a distinct and topographically-defined tumor microenvironment that emerges during multiple myeloma evolution. Blood Cancer Discov (2026).","DOI":"10.1158\/2643-3230.BCD-26-0080"},{"key":"2026092603350883000_2026.09.22.753531v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2016.04.002"},{"key":"2026092603350883000_2026.09.22.753531v1.40","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s10555-020-09943-1","article-title":"Macrophages in multiple myeloma: key roles and therapeutic strategies","volume":"40","year":"2021","journal-title":"Cancer Metastasis Rev"},{"key":"2026092603350883000_2026.09.22.753531v1.41","doi-asserted-by":"publisher","DOI":"10.1111\/tan.12478"},{"key":"2026092603350883000_2026.09.22.753531v1.42","doi-asserted-by":"crossref","unstructured":"Sordo-Bahamonde, C. et al. Beyond the anti-PD-1\/PD-L1 era: promising role of the BTLA\/HVEM axis as a future target for cancer immunotherapy. Mol Cancer 22, 142 (2023).","DOI":"10.1186\/s12943-023-01845-4"},{"key":"2026092603350883000_2026.09.22.753531v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.09.019"},{"key":"2026092603350883000_2026.09.22.753531v1.44","doi-asserted-by":"crossref","unstructured":"Yang, R. et al. Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade. J Immunother Cancer 8 (2020).","DOI":"10.1136\/jitc-2020-000610"},{"key":"2026092603350883000_2026.09.22.753531v1.45","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1158\/1535-7163.MCT-25-0130","article-title":"The Discovery and Characterization of HBS-101, a Novel Inhibitor of Midkine, as a Therapeutic Agent for the Treatment of Triple-Negative Breast Cancer","volume":"24","year":"2025","journal-title":"Mol Cancer Ther"},{"key":"2026092603350883000_2026.09.22.753531v1.46","doi-asserted-by":"crossref","first-page":"5436","DOI":"10.1182\/bloodadvances.2025016276","article-title":"HLA-E[pHLA-G] complex-specific monoclonal antibody enhancing NK activity in multiple myeloma","volume":"9","year":"2025","journal-title":"Blood Adv"},{"key":"2026092603350883000_2026.09.22.753531v1.47","doi-asserted-by":"crossref","unstructured":"Zhao, Z. et al. Decoding multiple myeloma: single-cell insights into tumor heterogeneity, immune dynamics, and disease progression. Front Immunol 16, 1584350 (2025).","DOI":"10.3389\/fimmu.2025.1584350"},{"key":"2026092603350883000_2026.09.22.753531v1.48","doi-asserted-by":"crossref","unstructured":"Rasche, L. et al. Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing. Nat Commun 8, 268 (2017).","DOI":"10.1038\/s41467-017-00296-y"},{"key":"2026092603350883000_2026.09.22.753531v1.49","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ccell.2025.12.009","article-title":"Spatial omics at the forefront: emerging technologies, analytical innovations, and clinical applications","volume":"44","year":"2026","journal-title":"Cancer Cell"},{"key":"2026092603350883000_2026.09.22.753531v1.50","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.ajpath.2026.03.014","article-title":"Next-Generation Disease Profiling by Integrating Histopathology with Spatial Multi-Omics Data","volume":"196","year":"2026","journal-title":"Am J Pathol"},{"key":"2026092603350883000_2026.09.22.753531v1.51","doi-asserted-by":"crossref","unstructured":"Cooper, R.A. et al. Redefining the topology of the human bone marrow using augmented spatial transcriptomic analysis. bioRxiv, 2025.2012.2022.694222 (2025).","DOI":"10.64898\/2025.12.22.694222"},{"key":"2026092603350883000_2026.09.22.753531v1.52","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/s41568-026-00922-2","article-title":"Advancing AI for multi-omics and clinical data integration in basic and translational cancer research","volume":"26","year":"2026","journal-title":"Nat Rev Cancer"},{"key":"2026092603350883000_2026.09.22.753531v1.53","doi-asserted-by":"crossref","unstructured":"Bankhead, P. et al. QuPath: Open source software for digital pathology image analysis. Sci Rep 7, 16878 (2017).","DOI":"10.1038\/s41598-017-17204-5"},{"key":"2026092603350883000_2026.09.22.753531v1.54","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.453"},{"key":"2026092603350883000_2026.09.22.753531v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-00998-0"},{"key":"2026092603350883000_2026.09.22.753531v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0638-x"},{"key":"2026092603350883000_2026.09.22.753531v1.57","doi-asserted-by":"crossref","unstructured":"Watson, E.C.R. et al. Belantamab Mafodotin Triggers Immune Invigoration in Multiple Myeloma Via Inflammatory and Immunogenic Cell Death. medRxiv, 2025.2009.2011.25335116 (2025).","DOI":"10.1101\/2025.09.11.25335116"},{"key":"2026092603350883000_2026.09.22.753531v1.58","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/bs.mie.2023.07.006","article-title":"Mass cytometry as a tool in target validation and drug discovery","volume":"690","year":"2023","journal-title":"Methods Enzymol"},{"key":"2026092603350883000_2026.09.22.753531v1.59","doi-asserted-by":"publisher","DOI":"10.1038\/S41587-023-01767-Y"},{"key":"2026092603350883000_2026.09.22.753531v1.60","doi-asserted-by":"crossref","unstructured":"Wu, L. , Beechem, J.M. & Danaher, P . Using transcripts to refine image based cell segmentation with FastReseg. Sci Rep 15, 30508 (2025).","DOI":"10.1038\/s41598-025-08733-5"},{"key":"2026092603350883000_2026.09.22.753531v1.61","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01664-3"},{"key":"2026092603350883000_2026.09.22.753531v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01358-2"},{"key":"2026092603350883000_2026.09.22.753531v1.63","doi-asserted-by":"crossref","unstructured":"Street, K. et al. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics 19, 477 (2018).","DOI":"10.1186\/s12864-018-4772-0"},{"key":"2026092603350883000_2026.09.22.753531v1.64","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01045-4"},{"key":"2026092603350883000_2026.09.22.753531v1.65","doi-asserted-by":"publisher","DOI":"10.1109\/mcse.2007.55"},{"key":"2026092603350883000_2026.09.22.753531v1.66","unstructured":"Korotkevich, G. et al. Fast gene set enrichment analysis. bioRxiv, 060012 (2021)."},{"key":"2026092603350883000_2026.09.22.753531v1.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17800-6"},{"key":"2026092603350883000_2026.09.22.753531v1.68","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty191"},{"key":"2026092603350883000_2026.09.22.753531v1.69","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.73600.2"},{"key":"2026092603350883000_2026.09.22.753531v1.70","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-00795-2"},{"key":"2026092603350883000_2026.09.22.753531v1.71","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.molcel.2025.12.026","article-title":"Delineating the copy-number substructure of metastatic tumors with CopyKit","volume":"86","year":"2026","journal-title":"Mol Cell"},{"key":"2026092603350883000_2026.09.22.753531v1.72","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.147"},{"key":"2026092603350883000_2026.09.22.753531v1.73","doi-asserted-by":"crossref","unstructured":"Argelaguet, R. et al. MOFA+: a statistical framework for comprehensive integration of multi-modal single-cell data. Genome Biol 21, 111 (2020).","DOI":"10.1186\/s13059-020-02015-1"},{"key":"2026092603350883000_2026.09.22.753531v1.74","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAB1038"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.22.753531","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:35:26Z","timestamp":1790418926000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.22.753531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":74,"URL":"https:\/\/doi.org\/10.64898\/2026.09.22.753531","relation":{},"subject":[],"published":{"date-parts":[[2026,9,23]]},"subtype":"preprint"}}