Phenome Centre Birmingham

PCB LogoThe £8M Phenome Centre Birmingham is a large metabolic phenotyping facility led by internationally-recognised metabolomics and clinical experts at the University of Birmingham. 

The Centre is primarily located in the School of Biosciences, and is a collaboration between the College of Life and Environmental Sciences and College of Medical and Dental Sciences.

The Centre provides extensive capacity and capability to perform small-scale and large-scale metabolic phenotyping of the human population for stratified medicine. The Centre works towards improving healthy ageing and disease diagnosis and treatment to enhance patient outcome including in toxicological response to drugs and the exposome.

Find out more at the Phenome Centre Birmingham website

Why work with us?

Phenome Centre Birmingham is dedicated to the high quality study of metabolites in biological systems to derive high quality data to understand the roles of metabolites in human health, ageing and disease.

Phenome Centre Birmingham resides within two purpose-built, fully-equipped facilities that was largely funded through a UK Stratified Medicine initiative led by the Medical Research Council (MRC) along with support from the University of Birmingham, Birmingham Health Partners and scientific instrument companies (Beckman Coulter, Bruker, Thermo Scientific and Waters).

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The centre provides a collaboration project environment for performing metabolic phenotyping studies in humans and model organisms. Experts in experimental design, analytical chemistry, bioinformatics and statistics to provide all required aspects of the study from conception to biological interpretation staff the centre.

Who do we work with?

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Phenome Centre Birmingham works with biomedical research groups in academia, healthcare provision (including the NHS), research institutes and industry including pharma.

Currently the centre collaborates with researchers in the UK and globally to undertake metabolic phenotying (metabolomics) in a wide range of different projects in areas including endocrinology, cancer, trauma, drug toxicity, neurodevelopmental disorders, musculoskeletal ageing, exercise and toxicology.

Phenome Centre Birmingham conducts metabolic phenotyping studies with the following objectives:

  • To understand molecular mechanisms associated with human ageing, disease onset and progression 
  • To identify molecular targets for nutritional, exercise or drug interventions
  • To identify metabolic biomarkers for stratification of the human population to be applied in risk stratification of developing a specific disease, in diagnosis of a disease, in defining progression or remission from a disease, and in the identification of responders and non-responders to nutritional, exercise or drug interventions

For more information regarding how to get in touch with Phenome Centre Birmingham, please use the contact details at the bottom of this webpage.

Resources and Services

Phenome Centre Birmingham offers a complete collaborative service to provide expertise and advice to perform metabolic phenotyping studies from conception and experimental design through data acquisition to data analysis and biological interpretation.

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Sample types: We provide the capabilities to study a diverse range of sample types. For large-scale metabolic phenotyping studies we recommend the use of biofluids including serum, plasma and urine. We also provide the capability to analyse other biofluids (e.g. CSF), tissues (e.g. liver or muscle) and cell lines.

Non-Targeted Metabolomics: applied when a broad survey of different classes of metabolites is required in discovery-based studies and provides relative quantification data on thousands of metabolites. We have an established analytical workflow that combines state of the art nuclear magnetic resonance (NMR) spectroscopy and ultra-high performance chromatography coupled with high resolution mass spectrometry (UHPLC-MS) to produce high quality data representing thousands of metabolites present in diverse areas of metabolism including amino acid metabolism, lipid metabolism and purine metabolism.

Four specific analytical methodologies are applied:

  • 1H NMR spectroscopy for a broad coverage of high concentration lipophilic and hydrophilic metabolites; typically up to 100 metabolites are detected and quantified
  • Hydrophilic Interaction Liquid Chromatography coupled to mass spectrometry (HILIC-MS) for a broad coverage of hydrophilic metabolites
  • Reversed phase UHPLC-MS for broad coverage of lipophilic metabolites including for lipidomic studies.
  • Biocrates p400 kit applying Direct Infusion Mass Spectrometry and UPLC-MS

To ensure the quality of data meets defined acceptance criteria our fully-trained team applies standard operating procedures and quality control samples for all studies. The data is processed, interrogated and analysed using standardised computational workflows. Our workflows include tools to visualise data quality, to apply biostatistics, and to identify metabolites. The identification of biologically or clinically significant metabolic markers (biomarkers), derived from biostatistical analysis and initial metabolite annotation, can be validated by the use of targeted assays (see below - Targeted Metabolomics).

Our facilities include:

  • Four Acquity UPLC systems with 2777c sample managers coupled to electrospray Xevo G2-XS QTof mass spectrometers (Waters)
  • Three Ultimate3000 RSLC UHPLC systems coupled to electrospray Q Exactive Focus mass spectrometers (Thermo Scientific)
  • Two 600MHz NMR spectrometers each with a room temperature 5mm probe (Bruker)
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Targeted Metabolomics: applied when a small and pre-defined set of metabolites are required to be investigated and provides absolute quantification data on tens of metabolites. In cases where the metabolites of interest are known we offer targeted assays to detect and quantify a small number of related metabolites. These metabolites may be linked based on metabolic class or biological function (e.g. amino acids) to allow a specific metabolic pathway to be studied or can be metabolic biomarkers from different metabolic pathways requiring validation and subsequent translation in to clinical use. Metabolites are quantified using targeted analytical methods on triple quadrupole mass spectrometers coupled with ultra-high performance chromatography, which produces true quantitative data. A range of targeted assays are available and research-specific targeted assays can be developed on request.

Our facilities include:

  • Two Ultimate3000 RSLC UHPLC systems coupled to electrospray Quantiva triple quadrupole mass spectrometers (Thermo Scientific)
  • One Acquity UPLC system with 2777c sample manager coupled to electrospray Xevo TQ-S triple quadrupole mass spectrometer (Waters)

Compound Identification: Often within the scientific literature the statistically significant and biologically important metabolites discovered in non-targeted metabolomics studies are not identified. Biological interpretation and validation of biomarkers require the chemical identification of the metabolites discovered in non-targeted studies. If sufficient sample is available then metabolite identification can be performed in Phenome Centre Birmingham by a combination of solvent/SPE/chromatographic fractionation, NMR spectroscopy and sequential mass spectrometry fragmentation experiments (MSn).

Our facilities include one electrospray LTQ-Orbitrap Elite mass spectrometer equipped with nanoLC and 2D-LC capabilities (Thermo Scientific) and nanoelectrospray infusion capabilities using the Advion Triversa Nanomate system

Data Processing, Biostatistical Analysis and Metabolite Annotation: The data is processed, interrogated and analysed using standardised and reproducible computational workflows. The workflows include tools, written in the R programming language and Python, to visualise data quality, to apply biostatistics, and to annotate metabolites or potential biomarkers. The workflows have been integrated into the Galaxy workflow management system [https://galaxyproject.org].  We apply a range of univariate and multivariate statistical approaches, dependent on the experimental design, to robustly discover metabolites that contribute to the differences related to the biological or clinical question.

Current Research

Currently the centre collaborates with researchers in the UK and globally to undertake metabolic phenotying (metabolomics) in a wide range of different projects in areas including endocrinology, cancer, trauma, drug toxicity, neurodevelopmental disorders, musculoskeletal ageing, exercise and toxicology.

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Recent Publications

Identification of the functional pathways altered by placental cell exposure to high glucose: lessons from the transcript and metabolite interactome. Hulme CH, Stevens A, Dunn W, Heazell AEP, Hollywood K, Begley P, Westwood M, Myers JE. Sci Rep. 2018 Mar 27;8(1):5270. doi: 10.1038/s41598-018-22535-y.

Exercise and high-fat feeding remodel transcript-metabolite interactive networks in mouse skeletal muscle. Pérez-Schindler J, Kanhere A, Edwards L, Allwood JW, Dunn WB, Schenk S, Philp A. Sci Rep. 2017 Oct 18;7(1):13485. doi: 10.1038/s41598-017-14081-w.

Untargeted metabolomic analysis and pathway discovery in perinatal asphyxia and hypoxic-ischaemic encephalopathy. Denihan NM, Kirwan JA, Walsh BH, Dunn WB, Broadhurst DI, Boylan GB, Murray DM. J Cereb Blood Flow Metab. 2017 Jan 1:271678X17726502. doi: 10.1177/0271678X17726502.

AKR1C3-Mediated Adipose Androgen Generation Drives Lipotoxicity in Women With Polycystic Ovary Syndrome. O'Reilly MW, Kempegowda P, Walsh M, Taylor AE, Manolopoulos KN, Allwood JW, Semple RK, Hebenstreit D, Dunn WB, Tomlinson JW, Arlt W. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3327-3339. doi: 10.1210/jc.2017-00947.

Collection and Preparation of Clinical Samples for Metabolomics. Chetwynd AJ, Dunn WB, Rodriguez-Blanco G. Adv Exp Med Biol. 2017;965:19-44. doi: 10.1007/978-3-319-47656-8_2.

Metabolomics enables precision medicine: "A White Paper, Community Perspective". Beger RD, Dunn W, Schmidt MA, Gross SS, Kirwan JA, Cascante M, Brennan L, Wishart DS, Oresic M, Hankemeier T, Broadhurst DI, Lane AN, Suhre K, Kastenmüller G, Sumner SJ, Thiele I, Fiehn O, Kaddurah-Daouk R; for “Precision Medicine and Pharmacometabolomics Task Group”-Metabolomics Society Initiative. Metabolomics. 2016;12(10):149.

Carbohydrate and fatty acid perturbations in the amniotic fluid of the recipient twin of pregnancies complicated by twin-twin transfusion syndrome in relation to treatment and fetal cardiovascular risk. Dunn WB, Allwood JW, Van Mieghem T, Morris RK, Mackie FL, Fox CE, Kilby MD. Placenta. 2016 Aug;44:6-12. doi: 10.1016/j.placenta.2016.05.012.

Dual-5α-Reductase Inhibition Promotes Hepatic Lipid Accumulation in Man. Hazlehurst JM, Oprescu AI, Nikolaou N, Di Guida R, Grinbergs AE, Davies NP, Flintham RB, Armstrong MJ, Taylor AE, Hughes BA, Yu J, Hodson L, Dunn WB, Tomlinson JW. J Clin Endocrinol Metab. 2016 Jan;101(1):103-13. doi: 10.1210/jc.2015-2928.

Contact Us

'General enquiries about the Phenome Centre Birmingham, should be directed to the Operations Manager - Dr Cate Winder (c.l.winder@bham.ac.uk), Professor Warwick Dunn (w.dunn@bham.ac.uk) for clinical metabolomics or Professor Mark Viant (m.viant@bham.ac.uk) for toxicology and metabolomics.

To find out more:  https://www.birmingham.ac.uk/research/activity/phenome-centre/index.aspx