MODIRen

Integrative metabolomics and genomics analysis for the development of markers of inherited kidney diseases: a personalised medicine approach

The focus of this 2-year long research and training project is on three rare inherited kidney diseases (RIKDs), namely Thin Basement Membrane Nephropathy (TBMN), CFHR5 nephropathy and MUC1 kidney disease. These RIKDs are characterised by a high degree of phenotypic heterogeneity and by the absence of biomarkers for disease diagnosis, prognosis and inadequate therapeutic management. The main aim of MODIRen is to develop new disease ontology for these three RIKDs using a deep-phenotyping approach.

In doing so, it will integrate phenotypic and genetic data for biomarker discovery and provide new knowledge for the development of a novel theranostic tool. As the project host, the Molecular Medicine Research Center, has started employing whole exome sequencing (WES) of cases and controls, for the identification of relevant genetic variants.

Among the tasks of the MODIRen is to provide a vital genotype-phenotype framework from which future theranostic tools can be more precisely designed and evaluated, towards precision medicine. Furthermore, it will provide the platform for complementing the researcher’s skills in metabolomics and systems biology with the MMRC’s expertise in genomics and molecular diagnostics to enhance the professional maturity of the main researcher and facilitate new international research and innovation initiatives and multidisciplinary collaborations. Marie Sklodowska-Curie Individual Fellowships are oriented towards supporting translational and intersectoral mobility and career development of researchers.

Subsequently, by using a dual biofluid-dual platform approach to maximise metabolome coverage, the metabolic profiles of healthy individuals will be compared to those of RIKD patients to identify disease-specific metabolic markers. Rigorous data analysis methodologies will be employed to integrate WES, metabolomic and clinical data for the identification of robust composite genotype-phenotype signatures of the diseases. These will elucidate molecular disease pathomechanisms, enabling better clinical diagnostics and improve patient stratification. MODIRen will provide a vital genotype-phenotype framework from which future theragnostic tools can be more precisely designed and evaluated, towards precision medicine