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

Project Information

MODIRen

Grant agreement ID: 893699

DOI

10.3030/893699

Project closed

EC signature date 6 April 2020

Start date 4 January 2021

End date 3 January 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 145 941,12

EU contribution

€ 145 941,12

Coordinated by

UNIVERSITY OF CYPRUS
Cyprus

Periodic Reporting for period 1 - MODIRen (Integrative metabolomics and genomics analysis for the development of markers of inherited kidney diseases: a personalised medicine approach)

Reporting period: 2021-01-04 to 2023-01-03

Summary of the context and overall objectives of the project

The focus of MODIRen 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 was to develop new disease ontology for these three RIKDs using a deep-phenotyping approach.

Main objectives of the project:
Metabolic profiling of urine and plasma samples from patients and healthy controls
Integration of metabolomics data with orthogonal genetic and clinical data
Facilitate the researcher's development into a leading expert in the field of metabolomics, as well as enable her to disseminate her expertise to research institutions, companies, and the public.
Metabolic, genetic and clinical data were integrated for biomarker discovery and to provide new knowledge for the development of a novel disease management tools. MODIRen provided a vital genotype-phenotype framework from which these tools can be more precisely designed and evaluated, towards precision medicine. The project's results will serve as the basis for improving clinical diagnostics and patient stratification as well as for designing theranostic tools.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The project focused on the development of new ontology for three rare inherited kidney diseases. The main research carried out in this project involved the study of biomarkers associated with renal conditions of monogenic Mendelian inheritance, including TBMN, CFHR5 nephropathy, and MUC1 kidney disease. The study leveraged samples stored at biobank.cy such as plasma and urine biospecimens, as well as clinical data, to identify functional biomarkers for these diseases. Metabolomics, being the closest to the phenotype from all other omics, captures information from all levels of biological organisation and is uniquely positioned to deliver insights into these diseases which are currently not well understood and for which pharmacological targets are not curative. Metabolomics approaches were employed to detect and quantify metabolites, and multivariate data analysis techniques were used to identify metabolic variation associated with differences between disease groups, disentangle within-group phenotypic heterogeneity and identify therapeutic targets. Specifically, for MUC-1 kidney disease metabolomics data was integrated with other omics and advanced mathematical modelling shedding light on a poorly characterised disease with limited prognostic and treatment tools available.

The Dissemination & Communication activities are:
- The researcher attended international conferences
- Social media dissemination through Facebook Twitter and LinkedIn
- Dedicated website: https://biobank.cy/portfolio/modiren/
- The researcher was interviewed on national television
- Participated at the European Researcher's Night in 2022

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

To our knowledge, this is the first study in less complex patients’ cohorts of monogenic diseases that follows such an integrative approach in rare inherited kidney disease, which are currently not well characterised or understood and for which pharmacological treatments are not curative, leveraging recent technological advances in omics technologies and bioinformatics. The proposed methodology maximises the potential of minimally/ non-invasive biomarker discovery for disease characterisation and elucidation of targets for treatments. The identification of biomarkers that modify the clinical course of prevalent Mendelian nephropathies in Cyprus will inform the design of a novel, robust diagnostic tool targeted to this population and offered in a routine clinical setting. As the prices of genomics and metabolomics analyses drop, such a tool can be easily used in the clinic, replacing expensive tests used today. In turn, this work opens doors for collaboration between industrial and academic parties for the discovery of new druggable targets and the development of novel theranostic tools. This study has a huge potential for better clinical diagnostics, efficient patient stratification and assessment of therapeutic responses. MODIRen can serve as an exemplar for precision nephrology services to the wider population with glomerulopathies, beyond these specific RIKDs. Additionally, the implementation of metabolomics in the realm of biobank.cy’s activities will result in innovative research advancements, in the framework of the first biobank in Cyprus and the study of genetic diseases.

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