MRC-NIHR National Phenome Centre

Transcription

1 MRC-NIHR National Phenome Centre

2 PROFESSOR JEREMY NICHOLSON Director of the MRC-NIHR National Phenome Centre OUR PHILOSOPHY Disease risk at the individual and population level is determined by complex throughout life interactions of human genes and environment. These same interactions create our metabolic phenotypes, which are reflective of disease risks and variations in responses to therapies. Our aim is to help maximise the efficiency of translational medicine in key areas of unmet medical need. Our History LONDON 2012 OLYMPIC LEGACY Funded by the MRC and NIHR with two facilities in Imperial College London the MRC- NIHR National Phenome Centre s business model is to provide bioanalytical, metabonomics, and informatics related client focused research solutions to scientists and innovators. Lead by Imperial College London and King s College London the Centre has a multidisciplinary team of specialists in biochemistry, the analytical platforms and informatics to enable the translation of the technology into routine clinical and biotechnology applications. The Centre takes advantage of an unprecedented opportunity offered by the legacy of the 2012 Olympics state-of-the-art drug testing analytical laboratory. Flexibility to meet national needs MOLECULAR PHENOTYPING The Centre is structured to offer broad and deep phenotyping on both large (over 5,000 samples) and small (fewer than 300 samples) human sample cohorts with a current operational capacity of 200,000 assays per year with the intention to significantly expand capacity in the next two years. END-TO-END RESEARCH SOLUTIONS Through a combination of scientific expertise, a comprehensive assay portfolio and a commitment to research and technology development the MRC-NIHR National Phenome Centre provides clients with the metabonomic solutions they require to advance their research programs.

3 Working with Us COMMITMENT TO CLIENT CENTRICITY The goal is to build long-term relationships with clients through a customisable and adaptable molecular phenotyping research opportunities. SOLUTIONS FOR SYSTEMS BIOLOGY Outsourcing metabolic profiling to the MRC-NIHR National Phenome Centre is a strategy that allows each partner to maximise productivity and focus their resources and energies on their core competencies. The Centre provides data of the highest quality as every project is customised to each client. SERVICE The Centre performs projects on a fee-for-service basis including limited data interpretation and establishment of a biological context on samples provided by the client. This service model allows both partners to develop a relationship and establish trust in their respective scientific expertise to move forward to an integrated collaboration or strategic partnership. INTEGRATED COLLABORATION Consistent with the MRC-NIHR National Phenome Centre s combined approach to scientific investigations the integrated collaboration model provides partners with industry-leading metabonomics capabilities as an extension of their own research programs. This leverages both the strengths and collective knowledge of the Centre and partner organisation. The MRC-NIHR National Phenome Centre alliance with Imperial College London Division of Computational and Systems Medicine provides clients with access to the highest level of services, best-in-class technology platforms, and access to a panel of top scientists, ensuring the most comprehensive capabilities in the industry. FOCUSED ON YOUR NEEDS The MRC-NIHR National Phenome Centre s business model reflects the strategy to provide flexible access to world leading facilities in metabolite analysis while sharing the risk and rewards. In close collaboration with clients, the Centre proposes a tailor-made solution utilising one or multiple platforms to achieve their research goals. STRATEGIC PARTNERSHIP Strategic partnerships are based on the agreement and alignment of the partner s activities with the MRC-NIHR National Phenome Centre s own projects and metabolomics research services. On specific large-scale projects or during a given time frame such an alliance is a flexible way of working with partners to help accomplish mutual goals.

4 Capabilities MRC-NIHR NATIONAL PHENOME CENTRE MULTIDISCIPLINARY APPROACH The Centre has developed the technology and expertise to provide metabolite analysis for a single biochemical to broad metabolite profiling using multiple assays to cover the diverse physiochemical properties of metabolites. No one technology platform or assay can provide the comprehensive coverage of the metabolome needed to provide insight into complex biological processes which is why the MRC-NIHR National Phenome Centre has developed and implemented two distinct but customisable research offerings. The Centre has the capacity to deliver high quality, low cost, broad and deep metabolic phenotyping of a large scale for both molecular epidemiology and experimental medicine studies with the added capability of multiomics and clinical metadata fusion and modelling for a wide variety of disease states and risk factors. Broad & Deep Metabolite Profiling METABONOMICS PLATFORM The MRC-NIHR National Phenome Centre non-biased broad metabolite profiling platform presents an opportunity to evaluate thousands of endogenous biochemicals as well as drug derived metabolites in a series of analyses. The Centre offers complementary NMR and assays to maximise metabolome coverage. These services are modular and can be tailored to the sample volume or matrix requirements. NMR can provide very valuable information on sample quality and constitutes a first line profiling analysis for the most abundant metabolites. The NMR assays have a high degree of annotation and can be used in a stand-alone analysis providing quantitative measurements for analytes such as lipoproteins. Additionally the MRC-NIHR National Phenome Centre developed NMR pre-screen offers a more robust analysis.

5 METABOLITE ASSAYS PROFILING The profiling assays provide an unprecedented metabolic coverage, comprising quantification or relative quantification of hundreds of individual metabolites. The range of metabolic features that can be detected includes amino acids, carbohydrates, carbohydratephosphates and other glycolysis metabolites, Krebs-cycle metabolites, low molecular weight organic acids, organic amines, fatty acids, eicosanoids, steroids, bile acids, phospholipids, ceramides, triglycerides, peptides, vitamins, co-factors, and tetrapyrrole derivatives among many more. With capability for integrative analytical and omics data modelling, structure elucidation and an evolving analysis pipeline for functional interpretation of biological data the Centre offers a comprehensive end-to-end metabolite profiling platform. Urine Plasma & Serum Platform NMR (RP+) (RP-) (HILIC+) NMR (Lipid+) (Lipid-) (HILIC+) Coverage Broad spectral profile targeting different types of analytes Broad and deep metabolite coverage of moderately polar to moderately apolar species Complementary analyte coverage for moderately polar to moderately apolar species Broad and deep metabolite coverage of highly polar analytes Broad spectral profile targeting different types of analytes Broad and deep metabolite lipid species coverage Complementary lipid coverage Broad and deep metabolite coverage of highly polar analytes PIPELINE FOR DISCOVERY & VALIDATION The MRC-NIHR National Phenome Centre s global metabonomic approach can also be used standalone or as the first stage in a comprehensive strategy to pinpoint active pathways, which can be further interrogated by targeted or customised assays developed in the Centre.

6 Hypothesis Driven Analysis TARGETED ASSAYS The MRC-NIHR National Phenome Centre targeted assays, employing methodologies, have the potential for providing quantitative information on discrete metabolites or screening panels. ABSOLUTE QUANTIFICATION APPLICATIONS Experimental Medicine Population Health Sciences Personalised Healthcare Pharmaceutical Research Nutrition Research Isotope dilution /MS and multiple reaction monitoring of specific fragments from the metabolites of interest are used for absolute quantification. Analytes for which a suitable isotopically labelled standard are not available are considered targeted but not quantified and relative quantification is provided. Example assays include: Amino Compounds Eicosaniods Fatty Acids Bile Acids Acylcarnitines Phenols Urinary Biopanels ENSURING HIGH QUALITY STANDARDS Quality management activities are routinely performed in all aspects of laboratory operations. Sampling protocols are available to ensure high quality samples are obtained. The criteria for accepting an assay are in accordance with FDA and EMEA guidance. These principles have been incorporated into all MRC-NIHR National Phenome Centre SOPs. Post-analytical quality control performed by dedicated experts ensures that the data generated is valid and can proceed to the next stages of analysis. Immediate feedback is available to applicable personnel.

7 Leading the Way in Innovation CONTINIOUSLY ADVANCING OUR PRODUCT RANGE The Centre is embedded in the Division of Computational and Systems Medicine at Imperial College London ensuring it has a strong research and development pipeline driving innovation in metabolic phenotyping. New technological opportunities are quickly evaluated and further developed into routine platforms. The MRC-NIHR National Phenome Centre assay portfolio is therefore continuously improving and expanding. CUSTOMISED SOLUTIONS WORLD CLASS RESEARCH & INSTRUCTION TO ADVANCE METABOLIC SCIENCE Whilst the MRC-NIHR National Phenome Centre is an efficient and reliable supplier of these standard assays the Centre is also a trusted partner when it comes to developing novel or tailor-made assays, informatics solutions and processes. The Imperial International Phenome Training Centre offers specialised basic and advanced practical training in NMR, MS and Data Analysis. IIPTC courses provide an interactive platform to obtain tuition in all facets of metabolic profiling within a practical working environment. The state-of-the-art international training facility provides students, scientists and doctors from around the world with new skills, to gain handson experience of using analytical technology to study the metabolic profiling. COMPREHENSIVE COURSE PORTFOLIO Metabolic Phenotyping in Human Health and Disease Introduction to Mass Spectrometry Hands on LC-MS for Metabolic Profiling Advanced Mass Spectrometry Hands on NMR for Metabolic Profiling Hands on Data Analysis for Metabolic Profiling Drug Metabolism and Bioanalysis

8 ACCESS TO THE MRC-NIHR NATIONAL PHENOME CENTRE To encourage the extensive and appropriate use of the MRC-NIHR National Phenome Centre for human sample analysis, access is via an independent Committee. Applications to the Centre should be made using the application form. The form and more information pertaining to the application process is available on-line on the MRC- NIHR National Phenome Centre website. MRC-NIHR National Phenome Centre Imperial College London