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DATA INTEGRATION AND PHENOTYPIC FLEXIBILITY

Suzan Wopereis

Abstract

Health is characterized by the ability to continuously adapt in varying circumstances where multiple mechanisms of system flexibility are involved. Their ability to adapt can act as an indicator for maintenance or improvement of physiological function. The term ‘phenotypic flexibility’ expresses the cumulative ability of overarching physiological processes (e.g. metabolism, inflammation, oxidation) to return to homeostatic levels after short-term perturbations.

The EU NutriTech project aimed to demonstrate and validate that phenotypic flexibility is a sensitive biomarker of metabolic resilience and that it can serve as a measure of health. A key factor is determining the physiological relevance of specific changes in phenotypic flexibility in a healthy (sub)population, for example in response to a dietary intervention. Ideally, this is pursued by validation against established markers of health, but these do not exist. Alternatively, modifications in challenge responses can be correlated to established markers of disease or to long-term health outcomes (disease risk, longevity) in cohort studies for validation purposes which is not easy.

Therefore, new data integration methodology was introduced based on network-biology with the objective to allow for validation of biomarkers across studies to enhance scientific evidence for effects of dietary interventions on identified markers of phenotypic flexibility. Network analysis enables integration and visualization of multi-layered experimental datasets and prior knowledge. Data from 4 human studies focusing on phenotypic flexibility were available in the phenotype database and used for a multi-study analysis providing a metabolic syndrome reference network. When this reference network is combined with the NutriTech human study data, the resulting visualization shows how the caloric restriction diet has impacted biomarkers of phenotypic flexibility related to metabolic syndrome. The NutriTech data integration pipeline offers a sustainable knowledge resource and toolbox for assessment of health effects of nutritional interventions.

Acknowledgements: Financed by the European Commission in the 7th Framework Programme FP7, Grant agreement no: 289511


Keywords

phenotypic flexibility, biomarker, validation, multi study analysis, nutritional intervention




DOI: http://dx.doi.org/10.14748/ssp.v4i1.3959

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Suzan Wopereis

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