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Pekayvaz, K.* ; Losert, C. ; Knottenberg, V.* ; Gold, C.* ; van Blokland, I.V.* ; Oelen, R.* ; Groot, H.E.* ; Benjamins, J.W.* ; Brambs, S.* ; Kaiser, R.* ; Gottschlich, A.* ; Hoffmann, G.V.* ; Eivers, L.* ; Martinez-Navarro, A.* ; Bruns, N.* ; Stiller, S.* ; Akgöl, S.* ; Yue, K.* ; Polewka, V.* ; Escaig, R.* ; Joppich, M.* ; Janjic, A.* ; Popp, O.* ; Kobold, S. ; Petzold, T.* ; Zimmer, R.* ; Enard, W.* ; Saar, K.* ; Mertins, P.* ; Huebner, N.* ; van der Harst, P.* ; Franke, L.H.* ; van der Wijst, M.G.P.* ; Massberg, S.* ; Heinig, M. ; Nicolai, L.* ; Stark, K.*

Multiomic analyses uncover immunological signatures in acute and chronic coronary syndromes.

Nat. Med. 30, 1696-1710 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Acute and chronic coronary syndromes (ACS and CCS) are leading causes of mortality. Inflammation is considered a key pathogenic driver of these diseases, but the underlying immune states and their clinical implications remain poorly understood. Multiomic factor analysis (MOFA) allows unsupervised data exploration across multiple data types, identifying major axes of variation and associating these with underlying molecular processes. We hypothesized that applying MOFA to multiomic data obtained from blood might uncover hidden sources of variance and provide pathophysiological insights linked to clinical needs. Here we compile a longitudinal multiomic dataset of the systemic immune landscape in both ACS and CCS (n = 62 patients in total, n = 15 women and n = 47 men) and validate this in an external cohort (n = 55 patients in total, n = 11 women and n = 44 men). MOFA reveals multicellular immune signatures characterized by distinct monocyte, natural killer and T cell substates and immune-communication pathways that explain a large proportion of inter-patient variance. We also identify specific factors that reflect disease state or associate with treatment outcome in ACS as measured using left ventricular ejection fraction. Hence, this study provides proof-of-concept evidence for the ability of MOFA to uncover multicellular immune programs in cardiovascular disease, opening new directions for mechanistic, biomarker and therapeutic studies.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cells; Alpha
ISSN (print) / ISBN 1078-8956
e-ISSN 1546-170X
Journal Nature medicine
Quellenangaben Volume: 30, Issue: 6, Pages: 1696-1710 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Unit for Clinical Pharmacology (KKG-EKLiP)
Grants Chan Zuckerberg Foundation
German Cancer Aid
Else Kroner-Fresenius-Stiftung
European Union
Melanoma Research Alliance
International doctoral program 'i-Target: immunotargeting of cancer' - Elite Network of Bavaria
TANGO
Bavarian Cancer Research Center (BZKF)
German Centre for Cardiovascular Research (DZHK)
ERC
Corona Foundation
DFG
Deutsche Forschungsgemeinschaft (DFG)
Deutsche Herzstiftung e.V.
DZHK partner site project
Wilhelm-Sander-Stiftung
Ernst Jung Stiftung
ERC Advanced Grant under the European Union
Zuckerberg Foundation
Helmholtz Association
Forderprogramm fur Forschung und Lehre (FoeFoLe) of LMU Munich
Bavarian Research Foundation
Ernst und Berta Grimmke Stiftung
Hector Foundation
Fritz-Bender Foundation
PoC
European Research Council
Bundesministerium fur Bildung und Forschung
Bavarian Ministry for Economical Affairs
Institutional Strategy LMUexcellent of LMU Munich
Deutsche Forschungsgemeinschaft (German Research Foundation)