Clinical Omics Profiling

This subproject provides clinical and phenotypic data as well as Omics data of cohorts of patients with DCM and HN. All relevant clinical data of disease status will be collected in a comprehensive clinical phenotyping program at baseline. For DCM, endomyocardial biopsies will be obtained at baseline for clinical reasons with the aim to identify the aetiology of DCM. Clinical examination, echocardiography, cardiopulmonary exercise testing (CEPT), and laboratory analyses of blood samples will take place in 6 month intervals. For HN, kidney biopsies will be obtained from patients with high levels of proteinuria for clinical reasons to histopathologically diagnose the type of glomerulopathy. Healthy tissue will be obtained from kidneys of nephrectomized patients. The Omics profiling comprises RNA-seq analysis of whole blood cells and target tissue biopsies, complementary plasma and tissue proteomics as well as recording of patterns of circulating plasma miRNAs. Starting with comprehensive analysis of the alternative splicing (AS) patterns of healthy controls from the SHIP study as well as of DCM and HN patients, AS signatures specific for each disease will be identified and then correlated to changes in protein/miRNA profiles and clinical phenotypes. In combination with the other subprojects, a mechanistic understanding of the aetiology of the two diseases will be sought through elucidating involved AS events. This directly integrates with the overall goal of the network, to understand the role of AS in DCM and HN on a systems medicine level.