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

Project description

Metabolomics and genomics analysis for rare kidney diseases

Rare inherited kidney diseases (RIKDs) are a group of heterogeneous disorders that often lead to renal replacement therapy, severely compromising patients' quality of life. The EU-funded MODIRen project aims to address the lack of biomarkers for disease diagnosis, prognosis and therapy. Researchers will perform whole exome sequencing to identify genetic variants and adopt a deep-phenotyping approach to determine disease-specific metabolic markers. Alongside clinical information, this data will provide genotype–phenotype signatures and help delineate RIKD pathophysiology. The project's results will serve as the basis for improving clinical diagnostics and patient stratification as well as for designing theranostic tools.

Objective

Rare inherited kidney diseases (RIKDs) encompass over 150 different conditions. They often lead to patients requiring renal replacement therapy being a major cause of end stage renal disease, severely compromising the patients’ quality of life and posing a high financial burden in healthcare. They 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 the proposed work is to develop new disease ontology for three RIKDs (Thin Basement Membrane nephropathy, CFHR5 nephropathy and MUC1 kidney disease) using a deep-phenotyping approach. Phenotypic and genetic data will be integrated for biomarker discovery and to provide new knowledge for the development of a novel theranostic tool. Whole exome sequencing (WES) of cases and controls is currently underway at the host for the identification of relevant genetic variants. 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 improved patient stratification. The proposed work will provide a vital genotype-phenotype framework from which future theranostic tools can be more precisely designed and evaluated, towards precision medicine. The proposed research and training program will complement the applicant’s skills in metabolomics and systems biology with the host’s expertise in genomics and molecular diagnostics to enhance her professional maturity and facilitate new international research and innovation initiatives and multidisciplinary collaborations.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

UNIVERSITY OF CYPRUS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 145 941,12
Address
AVENUE PANEPISTIMIOU 2109 AGLANTZI
1678 Nicosia
Cyprus

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Region
Κύπρος Κύπρος Κύπρος
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 145 941,12
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