Spatial transcriptomics provides single cell expression profile and tissue architecture resulting in a comprehensive analysis. Bioinformatics challenges presented by this new data type are tackled, with a focus on alignment strategies, transcript annotation, spatial reconstruction, and visualisation and transcription analysis. The project aims at identifying cellular and molecular signature profiles for the contractile function, the connective tissue and matrix function and the inflammation and explore these and thereby pinpoint their role in mechanisms of disease and as potential drug targets. We will search patients with HFpEF (Heart Failure with preserved Ejection Fraction) and HFrEF (Heart Failure with reduced Ejection Fraction) for genes with expression profiles in common and for genes with expression profiles distinguishing the two diseases. Myocardial biopsies from patients undergoing CABG with a) normal diastolic and systolic function, b) with reduced EF, and c) with preserved EF and diastolic dysfunction will be studied. Sequencing of DNA and mRNA (RNAseq) will be used to study sequence variation (SNPsI and CNVsII) and gene expression in order to define differences between the two HF conditions and define temporal changes in gene expression in HFpEF. A similar comparison will also be performed between patients with hypertension with and without HFpEF or HFrEF. We will also study DNA methylation to see if there is a common or contrary pattern in patients with HFpEF and HFrEF respectively. Bioinformatics analyses include characterisation of expressed genes and interpretation of gene products (proteins) including investigations of sequence variations (SNPs and CNVs). Furthermore, proteins of interest will be analysed using system biology approaches, looking at functional and/or structural interactions using tools/databases like Interactome, KEGG and FunCoup. Structural calculations will be used in SNP studies in order to evaluate effects of mutations. It will be of special interest to integrate these techniques including cell metabolic studies.