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Project

BASELINE: BiomArkers to predict complex diseases EarLy IN lifE (R-6521)

BASELINE makes use of biological samples and knowledge obtained from the human biomonitoring surveillance programme set up by the Flemish Centre of Expertise on Environment and Health, i.e. the 1st Flanders Environment and Health Survey (FLEHS1) that included 3 cohorts (newborn, adolescents, and adults). BASELINE's aim is to add an additional layer to the human biomonitoring initiative and perform biomarker discovery and functional confirmation to identify biological marks for disease characterization and development. The innovation step is the identification of new DNA methylation biomarkers early in live (in childhood or adolescence) to predict the risk of developing complex diseases later in life. To this end, an analytical pipeline (including data science aspects) will be optimized to create proof-of-concept that candidate biomarkers discovered in an epidemiological study, can be used in patient stratification (personalized medicine) and in drug efficacy testing. This activity will strengthen the initial scientific discovery done in biological samples from human biomonitoring and will allow for stronger interactions and collaborations with pharmaceutical and biotechnological partners. At the same time, this will show the value of biobank and biomonitoring initiatives for potential industrial and commercial activities. More specifically, we aim to confirm initial observations and develop added-value for recently identified biomarkers for prediction and/or diagnosis of respiratory allergy (RA). The comparison between whole DNA methylation profiles of RA cases and controls revealed 83 differentially methylated regions (DMR) in blood of 11y old children. An overlap with DMR detected in cord blood and saliva from the same individuals revealed 2 DMR in common, located in allergy-related genes (GLI2, involved in IL4 signaling and Th2-response; and TM9SF2, involved in phagocytosis). These findings have been subject for first filing of a patent at VITO (Patent application number EP 15 169 841.2). Work in BASELINE will include: 1) confirmation of the applicability of biomarkers in clinical samples, including samples from various subtypes of allergic rhinitis; 2) study of the relevance of the methylation markers in predicting the efficacy of respiratory allergy/asthma therapies (e.g. anti-IL4), 3) confirmation of biomarkers in a new population cohort in the context of preventive screening (600 14-15y old children in the new Flemish policy-driven biomonitoring initiative). In addition, we will make a first evaluation of our approach and applicability of our analytical pipeline in the search of DNA methylation biomarkers for breast cancer development. We aim to tackle the following questions: 1) which DNA methylation changes can be identified as indicators for developing breast cancer by studying blood from women collected pre-diagnosis in the context of human biomonitoring; and 2) can we detect these identified breast cancer-related changes in teenagers and young women. The ultimate goal of this multidisciplinary project is to contribute to the development of new prevention strategies, particularly in young people, thereby reducing the family and societal burden associated with complex diseases such as allergy and breast cancer. Current research in this field has been hampered due to the very long assessment periods and the associated financial requirements. The increasing number of longitudinal biomonitoring programmes enables us to use pre-diagnosis biobanked samples, which accelerates the biomarker validation process.
Date:1 Oct 2015 →  31 Dec 2019
Keywords:Biomarkers
Disciplines:Applied mathematics in specific fields, Astronomy and space sciences, Classical physics, Materials physics, Mathematical physics, Quantum physics