Metabolomics Services

Preliminary activities

Project consultation
Your scientific lead will meet with you to provide advice and support the design and planning of your metabolomics study

Logistics support
Our operations team can advise on appropriate shipping options, provide necessary paperwork for customs clearance, or arrange a bespoke pickup using one of our liquid nitrogen dry shippers.

Analytical

Sample extraction
We use established manual and automated sample extraction methods, providing flexibility to suit all project sizes.

Ultra-high performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-MS).

We have established analytical workflows that apply state of the art analytical techniques, producing high quality data representing thousands of metabolites present in diverse areas of metabolism.

Computational

With years of research and development experience in the field of computational metabolomics, we have established an extensive portfolio of computational solutions to process and analyse high dimensional metabolomics data.

Our computational services at a glance:

• Well-established, standardised and reproducible workflows.
• Workflows cover a broad range of methods and approaches, including data processing and quality control, biostatistics and machine learning, and metabolite identification.
• We adapt and optimise our workflows to match the experimental design and exploit the full potential of the data.
• Leveraging our pre-existing workflows, and scalable and robust compute resources we have the ability to provide a quick and reliable turnaround time.
• A detailed and standardised project report, summarising the results and findings, will be generated and provided.
• We apply and use standards and best practices to help our customers achieve regulatory compliance.

Sample preparation

Automated extraction is completed using a Beckman Coulter™ Biomek i7™ Automated Workstation, customised for bespoke low-temperature metabolomics usage.

Analytical

Ultra-high performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-MS)

Our suite of high mass resolution mass spectrometers includes:

• Two Thermo Scientific™ Orbitrap Exploris™ 120 mass spectrometers each coupled to a Vanquish™ Flex Duo Binary UHPLC system
• One Thermo Scientific™ Orbitrap ID-X™ Tribrid™ mass spectrometer coupled to a Vanquish™ Horizon Binary UHPLC system

Considering our two UHPLC-Orbitrap Exploris™ systems, each instrument is dedicated to specific UHPLC-MS approaches – metabolomics or lipidomics, see below – which provides parallel analysis of your samples. Two assays are available:

• Hydrophilic interaction liquid chromatography (HILIC) UHPLC-MS assays provide a broad coverage of hydrophilic metabolites. Assays utilise:
  • a Waters ACQUITY Premier BEH Amide UHPLC column.
  • our dual channel Vanquish™ UHPLC system, which enables analysis of samples in positive and negative ion modes simultaneously enabling optimal mobile phase conditions for each assay.
• Reversed phase propan-2-ol based UHPLC-MS assays provide a broad coverage of lipophilic metabolites. Assays utilise:
  • a Waters ACQUITY Premier CSH C₁₈ UHPLC column.
  • our dual channel Vanquish™ UHPLC system, which enables analysis of samples in positive and negative ion modes simultaneously enabling optimal mobile phase and gradient conditions for each assay.

Our UHPLC-Orbitrap ID-X™ system is dedicated to metabolite and compound identification.

• The capabilities of the Tribrid™ component along with AcquireX™ software allow us to conduct in-depth MSⁿ.
• This approach provides deep metabolome annotation (DMA) of metabolites and compounds within biological samples.

Computational

Our robust, scalable and secure informatics infrastructure includes:

• BlueBEAR supercomputer - high performance computing cluster employs some of the latest solutions and technology to deliver fast and efficient processing capacity.
• Well-established, standardised and reproducible workflows build from a combination of open-source and proprietary software and tools.

Our team of researchers have developed and evaluated standard operating procedures to prepare samples from a diverse range of biological samples. We have robust SOPs to extract metabolites from multiple types of clinical samples, cells, culture media and many model organisms.

If your sample type is new to us, our team of experienced researchers can explore developing a new SOP for your study.

Sample Collection and Shipping

Appropriate sample collection, storage and shipping is essential to guarantee the quality of your samples when working in the metabolomics space. Our operations team will provide sample collection and shipping guidelines to ensure your samples reach us in optimal condition. We also offer a bespoke pickup using DHL Express with one of our CXR500 liquid nitrogen dry shippers, managed by our operations team.

Sample Type Examples:

• Serum/ Plasma
• Urine
• Cells (mammalian, suspension or adherent) - including HepG2, HepaRG, H295R
• Cerebrospinal fluid (CSF)
• Dried Blood Spots (DBS)
• Tissues – including liver, kidney, heart, muscle, lung, brain, cancer tissue.
• Saliva
• Model organisms; (e.g. Daphnia magna, Drosophila, Xenopus, Zebrafish, C. elegans)

Metabolite annotation / identification is a recognised major challenge in metabolomics. The Phenome Centre Birmingham Directors have been working on this challenge for around 20 years, and continue to push boundaries, leading and engaging with collaborative networks and partnerships - such as the Metabolomics Society Metabolite Identification Task Group - to maximise coverage and confidence in the identifications we provide.

For Phenome Centre Birmingham workflows, we address this challenge in several ways:

• We have incorporated the latest analytical developments and bioinformatics tools in our annotation / identification workflows, and continue to update and optimise workflows as new developments and tools are created.
• We run all data collected through our in-house annotation workflow, Birmingham mEtabolite Annotation for Mass Spectrometry (BEAMS).
• We run multiple Data Dependent Analysis experiments on project specific pooled QCs to maximise MS/MS data collected during the initial analysis. The MS/MS data is used to search external databases including Thermo Scientific™ LipidSearch™, mzCloud™, and our in-house spectral library containing ~300 metabolites.
• We apply accurate mass and MS/MS data and retention time (for metabolites in our in-house database) to provide confidence in the metabolites we identify.

Our facility has established workflows in place, designed to provide optimal support on a stage-by-stage basis, ensuring that you receive the best possible results from our service.

1. Scientific Lead

Your scientific lead is the primary contact for the duration of the project. They will guide you through the experimental design and select the appropriate methods for your study.

2. Project Setup

Our operations team will support your project set-up including ethics, contracts and any specific project requirements and once complete, provide guidance on how samples should be shipped to us.

3. Sample Preparation & Data Acquisition

Sample preparation and data acquisition will be undertaken by a dedicated analytical specialist using our optimised methods.

4. Metabolite Identification

Accurate mass, retention time and MS/MS data acquired via Data Dependent Analysis on project specific pooled QCs is applied to search internal and external databases.

5. Data Processing & Data Analysis

Our bioinformatics and biostatistics team will process the data, run our quality assurance procedure and perform the data analysis using defined workflows.

6. Our team will compile a report

Your report will be complied by our team of experts and reviewed by your scientific lead.

7. Delivering your results

Your scientific lead will communicate directly with you via face-to-face meeting or teleconference to aid your interpretation of the results.