Despite remarkable progress in the management of cardiovascular disease (CVD), major unmet needs remain with regard to mortality, hospitalisations, quality of life (QoL), healthcare expenditures and productivity. Acute coronary syndrome (ACS), atrial fibrillation (AF) and heart failure (HF) are major and growing components of the global CVD burden. Optimal management of these conditions is complicated by their complex aetiology and heterogeneous prognoses. Poor definition at the molecular level and co/multi-morbidities form major challenges for the development and delivery of targeted treatments. This renders response to therapy unpredictable, with large inter-individual variation and, importantly, small or undetectable treatment effects in large trials of unselected patients. Today’s treatment guidelines still reflect the scientific constraints of an earlier era where clinical markers to guide therapy are limited to conventional risk factors and end-organ damage, and where the main endpoint in clinical trials is patient death. Hence, drug development pipelines from early target validation through to late post-marketing work have proven to be slow, expensive and high-risk: the chance of eventual approval for a CVD drug candidate in Phase I trials is 7%, the lowest of any disease category (shared with oncology) 2. Moreover, tolerability of medication and adherence to treatment show wide variations. There is thus a need for better definition of these diseases, their markers and endpoints (including better segmentation of current heterogeneous patient groups acknowledging underlying mechanisms and comorbidities) and of their outcomes/prognoses (including functional capacity and quality of life [QoL]). BigData@Heart’s ultimate goal is to develop a Big Data--driven translational research platform of unparalleled scale and phenotypic resolution in order to deliver clinically relevant disease phenotypes, scalable insights from real-world evidence and insights driving

The Research empowerment on solute carriers (ReSOLUTE) proposal aims at inducing a decisive acceleration in the intensity of SLC research worldwide while establishing solute carriers (SLCs) as a tractable target class. It is composed of a core consortium of seven academic/SME members (CeMM, Univ. of Oxford, Univ. of Manchester, AXXAM Spa, Univ. Leiden, Max-Planck Institut für medizinische Forschung, Univ. Wien) and six industrial partners (Pfizer Limited UK, Novartis Pharma AG, Boehringer-Ingelheim, Vifor Pharma Group, Sanofi Aventis Recherche et Développement, Bayer AG) with established and complementary expertise combining industry grade standards and systems level principle-driven analysis. ReSOLUTE merges systematic and focused approaches: 1) the generation of reliable and validated ‘hardware’ such as cell lines, proteins, antibodies/high affinity binders and large ‘omics’ datasets, 2) a central deorphanisation process coupling genomic engineering to metabolomics and supported by genetic and proteomics studies, 3) a non-redundant process to test systematically the suitability of a certain SLC to a variety of assay formats, 4) a collection of interlinked networks that cover different expertise, datasets and functional connections among SLCs, integrated into large-scale data repositories and a dedicated knowledgebase. The ReSOLUTE strategy will be applied in parallel at the super-family level and, in a more in-depth manner, to a prioritized gene list elected to be potential drug targets. To implement this and achieve the expected goals, the consortium is supported by a large network of academic and industrial partners with specific knowledge of certain SLCs and tools, willing to be accessed at any time and provide specific expertise. Together with a strong dissemination and exploitation plan, we therefore expect that ReSOLUTE will transform the landscape of SLC research for years to come.