Multi-Omic Factor Analysis uncovers immunological signatures with pathophysiologic and clinical implications in coronary syndromes

Acute and chronic coronary syndromes (ACS and CCS) are leading causes of mortality. Inflammation is considered to be a key pathogenic driver, but immune states in humans and their clinical implications remain poorly understood. We hypothesized that Multi-Omic blood analysis combined with Multi-Omic Factor Analysis (MOFA) might uncover hidden sources of variance providing pathophysiological insights linked to clinical needs. Here, we compile a single cell longitudinal dataset of the circulating immune states in ACS & CCS (13x10[3][1] clinical & Multi-Omic variables, n=117 subjects, n=838 analyzed samples) from two independent cohorts. Using MOFA, we identify multilayered factors, characterized by distinct classical monocyte and CD4+ & CD8+ T cell states that explain a large proportion of inter-patient variance. Three factors either reflect disease course or predict outcome in coronary syndromes. The diagnostic performance of these factors reaches beyond established biomarkers highlighting the potential use of MOFA as a novel tool for multilayered patient risk stratification. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the DZHK partner site project [K.S.], DZHK Saeule B Antrag DZHK B 21014 SE [K.P., L.N., P.M. & N.H.] and DZHK project 81Z0600106 [M.H.]. Further, the project was supported by Deutsche Herzstiftung e.V., Frankfurt a.M. [K.P.], [L.N.], Deutsche Forschungsgemeinschaft (DFG) SFB 914 (S.M. [B02 and Z01], K.S. [B02]), the DFG SFB 1123 (S.M., L.N., B.E. [B06], K.S. [A07]), M.J and R.Z [Z02]), the DFG SFB1321 (B.E. [P10], S.M. [P10], the DFG FOR 2033 (S.M.), the DFG SFB1243 (W.E. [A14], the DFG EN 1093/21 (W.E., A.J.), LMUexcellent [K.P.], the DFG Clinician Scientist Programme PRIME (413635475, K.P., R.K.), the ERC-Starting grant T MEMORE (ERC grant 947611) [K.S.]) and the ERC Advanced grant IMMUNOTHROMBOSIS (ERC-2018-ADG [S.M.]) and the German Centre for Cardiovascular Research (DZHK) (Clinician Scientist Programme [L.N.], MHA 1.4VD [S.M.]). C.L. is supported by the Helmholtz Association under the joint research school Munich School for Data Science MUDS. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Ludwig-Maximilians-Universitaet Muenchen, Medizinische Fakultaet, gave ethical approval for this work (No.: 19-274) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: #ref-3