Title: Establishing MRC-NIHR Phenome Centre, a world leading high-throughput metabolic phenotyping centre for humanpopulation disease-risk biomarker discovery.
Funder: Department of Health and Social Care

Abstract: We are establishing the MRC-NIHR Phenome Centre, a world leading high-throughput metabolic phenotyping centre for human population disease-risk biomarker discovery. It will offer the scientific community a unique capability in targeted and exploratory metabolic phenotyping and assay development, as well as a computational medicine capability for the provision of data, models and physiological interpretation. Metabolic phenotypes (metabotypes) are strongly influenced by both host genes and environment, and their interaction. A multitude of factors modify the metabotype of both individuals and populations. These include gender, age, diet, gut microbiome, physical activity, latent disease, hormone and stress levels, as well as xenobiotics, such as medications, plasticisers, food preservatives, pesticides, and plant secondary metabolites such as caffeine, flavinoids and phytoestrogens. Biofluids, such as blood and urine, carry detailed metabolic and homeostatic information, providing a top-down 'systems biology' readout of the biochemical, physiological, dietary and environmental exposures of individuals. By taking advantage of the new -'omics' technologies, the end-products and consequences of these external challenges and internal responses ('the exposome') can be captured. Cross-integration of genetic and metabolic phenotype data will aid patient stratification through discovery of novel disease and prognostic biomarkers and better understanding of responses to treatment and novel therapies. The MRC-NIHR National Phenome Centre will provide, at scale, the ability to analyse both patient- and population-based samples for biomarker discovery and validation, improved patient stratification through development of robust diagnostic and prognostic markers, and early identification of drug efficacy, safety and other responses to treatments. The Centre will provide a service to the scientific community providing high-throughput analysis of their samples, providing unprecedented scale, quality control and reproducibility and will also engage in academic collaboration for some of the projects requiring complex data analysis and interpretation. The facility will comprise state-of-the-art Mass Spectrometry (MS) and high field Nuclear Magnetic Resonance (NMR) facilities at Imperial, and will be supported by strategic alliances with King's College London and major instrument suppliers of both MS (The Waters Corporation) and NMR (Bruker Biospin GmbH). The establishment of the Phenome Centre will be one of the most important developments in applied analytical science in teh UK in a generation. It will be transformational in the scale of what can be achieved. It will create a template for international harmonisation of the approach to metabolic phenotyping and its methodologies, for the first time making data at this level comparable across institutions. Finally the R&D input from the Centre's technology partners will transform the instrumentation and methods for analytical chemistry by undertaking R&D to develop new analytical methods, establish novel approaches to computational multivariate analyses and to develop the technology, eg to increase the throughput and reduce environmental impact.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE