{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:07:48Z","timestamp":1773763668866,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100027026","name":"Johnson and Johnson Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100027026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Signalling networks have been assessed in blood cells by assessing individual phosphoantigens. We considered the possibility that bivariate correlations involving a series of signalling molecules could be used to delineate functional signalling networks in cells from clinical samples. Here, we describe a novel approach to signalling network analysis using enhanced flow cytometry to provide increased resolving power and restricted\u2010dimensional cytometry which simplifies the analysis so that the precision of the analysis is optimised. This approach has been validated in short\u2010term cultures by recapitulating known tenets of two distinct pathways. Additionally, new findings from our unique approach provide both expanded and nuanced views of signalling circuits. Applying our technology platform to blood mononuclear cells from patients with plasma cell disorders, we identified cell\u2010type specific features of signalling pathways by distinct patterns of bivariate correlations. The intermolecular relationships between signalling analytes provide a description of the signalling network in blood cells from clinical samples. Consequently, our approach has the potential to assess how the blood mononuclear cell\u2010type specific signalling network affects pathophysiology and pathogenesis.<\/jats:p>","DOI":"10.1111\/jcmm.70550","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T11:55:32Z","timestamp":1750420532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Signalling Network Analysis of Blood Mononuclear Cells From Clinical Samples by Bivariate Correlation"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-9254","authenticated-orcid":false,"given":"David","family":"Kaplan","sequence":"first","affiliation":[{"name":"CellPrint Biotechnology LLC  Shaker Heights Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1159-5607","authenticated-orcid":false,"given":"Hillard M.","family":"Lazarus","sequence":"additional","affiliation":[{"name":"CellPrint Biotechnology LLC  Shaker Heights Ohio USA"},{"name":"Department of Medicine Case Western Reserve University  Shaker Heights Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Valent","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Center Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faiz","family":"Anwer","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Center Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Mazzoni","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Center Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christy","family":"Samaras","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Center Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Center Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Center Cleveland Clinic Foundation  Cleveland Ohio USA"},{"name":"Department of Pathology and Laboratory Medicine Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mazen","family":"Hanna","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Center Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahzad","family":"Raza","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Center Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Christian","sequence":"additional","affiliation":[{"name":"CellPrint Biotechnology LLC  Shaker Heights Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Khouri","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Center Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvy115"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.04.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11830"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.03.017"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.042762"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.138057"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.14207"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(20000501)40:1<81::AID-CYTO11>3.0.CO;2-K"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1309\/KXQ7-LHKC-CYQ8-R70W"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.241509398"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/0953710031000080577"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20103"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1309\/7C2VV961P60RMLHD"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-01-137018"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.20506"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2011.03.005"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.22059"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.22485"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23832"},{"issue":"1","key":"e_1_2_10_21_1","first-page":"8","article-title":"Protein Biomarkers in Monocytes and CD4+ Lymphocytes for Predicting Lithium Treatment Response of Bipolar Disorder: A Feasibility Study With Tyramine\u2010Based Signal\u2010Amplified Flow Cytometry","volume":"52","author":"Gao K.","year":"2022","journal-title":"Psychopharmacology Bulletin"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina59010120"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2023.02.058"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13051491"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100705\u2010y"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180139"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00037-14"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.34.10.1083"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201430"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010018\u20100089\u20108"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100279200"},{"key":"e_1_2_10_32_1","unstructured":"https:\/\/www.proteinatlas.org\/ENSG00000165025\u2010SYK\/immune+cell."},{"key":"e_1_2_10_33_1","unstructured":"https:\/\/www.proteinatlas.org\/ENSG00000189403\u2010HMGB1\/immune+cell."},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022113349"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2022.108998"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5337"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099993"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-018-0505-3"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00995.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2016.02.010"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460\u20109568.1998.00019.x"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.002"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70550","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T12:09:06Z","timestamp":1751026146000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.70550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":41,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/jcmm.70550"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.70550","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2024-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70550"}}