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Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-1-B | Award Amount: 15.82M | Year: 2012

EURenOmics will integrate several established consortia devoted to rare kidney diseases with eminent need and potential for diagnostic and therapeutic progress (i.e. steroid resistant nephrotic syndrome, membranous nephropathy, tubulopathies, complement disorders such a haemolytic uraemic syndrome, and congenital kidney malformations). The Consortium has access to the largest clinical cohorts assembled to date (collectively >10,000 patients) with detailed phenotypic information and comprehensive biorepositories containing DNA, blood, urine, amniotic fluid and kidney tissue. The project aims to (1) identify the genetic and epigenetic causes and modifiers of disease and their molecular pathways; (2) define a novel mechanistic disease ontology beyond phenotypical or morphological description; (3) develop innovative technologies allowing rapid diagnostic testing; (4) discover and validate biomarkers of disease activity, prognosis and treatment responses; and (5) develop in vitro and in vivo disease models and apply high-throughput compound library screening. For these purposes we will integrate comprehensive data sets from next generation exome and whole-genome sequencing, ChiP-sequencing, tissue transcriptome and antigen/epitope profiling, and miRNome, proteome/peptidome, and metabolome screening in different body fluids within and across conventional diagnostic categories. These data will be combined in a systems biology approach with high-resolution clinical phenotyping and findings obtained with a large array of established and novel in vitro, ex vivo and in vivo disease models (functiomics) to identify disease-associated genetic variants involved in monogenic or complex genetic transmission, disease-defining molecular signatures, and potential targets for therapeutic intervention. These efforts will converge in the development of innovative diagnostic tools and biomarkers and efficient screening strategies for novel therapeutic agents.


Cammaerts S.,Applied Genomics | Cammaerts S.,University of Antwerp | Strazisar M.,Applied Genomics | Strazisar M.,University of Antwerp | And 6 more authors.
Nucleic Acids Research | Year: 2015

Genetic variants in or near miRNA genes can have profound effects on miRNA expression and targeting. As user-friendly software for the impact prediction of miRNA variants on a large scale is still lacking, we created a tool called miRVaS. miRVaS automates this prediction by annotating the location of the variant relative to functional regions within the miRNA hairpin (seed, mature, loop, hairpin arm, flanks) and by annotating all predicted structural changes within the miRNA due to the variant. In addition, the tool defines the most important region that is predicted to have structural changes and calculates a conservation score that is indicative of the reliability of the structure prediction. The output is presented in a tabseparated file, which enables fast screening, and in an HTML file, which allows visual comparison between wild- Type and variant structures. All separate images are provided for downstream use. Finally, we tested two different approaches on a small test set of published functionally validated genetic variants for their capacity to predict the impact of variants on miRNA expression. ©The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. Source


Gielis E.M.,University of Antwerp | Gielis E.M.,Leiden University | Ledeganck K.J.,University of Antwerp | De Winter B.Y.,University of Antwerp | And 5 more authors.
American Journal of Transplantation | Year: 2015

After organ transplantation, donor-derived cell-free DNA (ddcfDNA) can be detected in the recipient's blood and urine. Different ddcfDNA quantification techniques have been investigated but a major breakthrough was made with the introduction of digital droplet PCR and massive parallel sequencing creating the opportunity to increase the understanding of ddcfDNA kinetics after transplantation. The observations of increased levels of ddcfDNA during acute rejection and even weeks to months before histologic features of graft rejection point to a possible role of ddcfDNA as an early, noninvasive rejection marker. In this review, we summarize published research on ddcfDNA in the transplantation field thereby elaborating on its clinical utility. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons. Source


Cammaerts S.,University of Antwerp | Strazisar M.,University of Antwerp | Rijk P.D.,University of Antwerp | Del Favero J.,University of Antwerp | Del Favero J.,Multiplicom
Frontiers in Genetics | Year: 2015

MicroRNAs (miRNAs) are important regulators of gene expression and like any other gene, their coding sequences are subject to genetic variation. Variants in miRNA genes can have profound effects on miRNA functionality at all levels, including miRNA transcription, maturation, and target specificity, and as such they can also contribute to disease. The impact of variants in miRNA genes is the focus of the present review. To put these effects into context, we first discuss the requirements of miRNA transcripts for maturation. In the last part an overview of available databases and tools and experimental approaches to investigate miRNA variants related to human disease is presented. © 2015 Cammaerts, Strazisar, De Rijk and Del Favero. Source


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-2 | Award Amount: 15.18M | Year: 2013

The ageing of the European population represents a rapidly rising social and economic challenge. Especially cardiovascular morbidity increases with age, but unfortunately, elderly patients are often difficult to diagnose due to confounding factors, leading to uncertainties in clinical decision making with huge impact on patients outcomes. Hence, there is an unmet need for novel biomarkers for more accurate diagnosis, risk assessment, and clinical outcome prediction for both acute and chronic cardiovascular diseases in the elderly. The BestAgeing consortium aims to improve this lack of diagnostic capabilities by developing and validating innovative omics-based biomarkers particularly for elderly patients supporting healthy ageing in Europe. Our study design addresses the most frequent and severe cardiovascular diseases of elderly patients by incorporating the appropriate disease cohorts and biomaterials from European populations. We aim to develop new omics-assays to diagnose cardiovascular disease, estimate risk, and monitor the response to treatment in elderly. This is envisaged to enable a more stratified and economic delivery of medicine. We expect that BestAgeing will generate novel European medical technologies that can improve the efficacy and efficiency of our care for elderly patients, which will also impact on socioeconomic wealth in Europe.

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