Lipidomics and metabolomics for rare disease diagnosis
Lead Research Organisation:
Swansea University
Department Name: Institute of Life Science Medical School
Abstract
One of the top priorities set out by the UK Rare Diseases Framework is to help patients get a final diagnosis faster. There are an estimated 6,000-8,000 rare diseases, including over 1,000 inborn metabolic disorders. The majority of rare disease patients experience the diagnostic odyssey, including diagnosis delay, misdiagnosis, or no correct diagnosis. Harnessing the power of gene technology for patient care has made a significant advance, but gene sequencing is mostly limited to diagnosing patients with known mutations. To further transform rare disease diagnosis, biochemical methods including metabolomics, and gene sequencing technology need to be developed together and integrated. Clinicians want more global and efficient assays which can identify what is the cause of the medical problem and can rule out other conditions in an initial assessment with a fast turnaround time.
UK academic laboratories specialising in mass spectrometry have world-leading expertise in global metabolite analysis, known as metabolomics. Currently this technology is only used in ad hoc research collaborations, and the majority of patients do not directly benefit from such recent technology developments.
To address the challenges in rare disease diagnosis, by bringing together, bioanalysts including experts in metabolomics, clinical scientists, clinicians, geneticists, biostatisticians and patient groups, from across the four nations of the UK, our node aims to establish new routes for clinical access to multiplexed lipidomic/metabolomic assays targeted at rare diseases, enabling earlier diagnosis, intervention and improved clinical outcomes.
UK academic laboratories specialising in mass spectrometry have world-leading expertise in global metabolite analysis, known as metabolomics. Currently this technology is only used in ad hoc research collaborations, and the majority of patients do not directly benefit from such recent technology developments.
To address the challenges in rare disease diagnosis, by bringing together, bioanalysts including experts in metabolomics, clinical scientists, clinicians, geneticists, biostatisticians and patient groups, from across the four nations of the UK, our node aims to establish new routes for clinical access to multiplexed lipidomic/metabolomic assays targeted at rare diseases, enabling earlier diagnosis, intervention and improved clinical outcomes.
Technical Summary
Mass spectrometry (MS) offers high specificity of metabolite identification and quantification and is routinely used for newborn screening and by NHS metabolic laboratories. Recent advances in MS based metabolomics and lipidomics allow the quantitative profiling of a large number (>1,000) of metabolites in a given sample. MS is a powerful tool to reveal biochemical abnormalities and to facilitate rare disease diagnosis in combination with genomics and other biochemical assays. This project will bring MS expertise from the UK lipidomic/metabolomic community into the domain of rare disease diagnosis. It will translate the latest lipidomic/metabolomic methods from a research settings to the clinical laboratory.
Specifically, we will:
(1) Translate enhanced screening assays for rare lipid and metabolic disorders from the research laboratory to the NHS metabolic laboratory.
(2) Integrate metabolomics with genomics for diagnosis of Syndromes Without A Name.
With further technological development, i.e., faster sample turn-around and lower cost, we aim to incorporate more lipidomic/metabolomic technology into the diagnostic pathways as well as considering its future application to newborn screening programmes, allowing asymptomatic patients to be identified and diagnosed. The node will be open to new members who bring in different "omic" expertise including bioinformaticians and economists, also to new clinical centres with the challenge of diagnosing patients with rare metabolic disorders.
Specifically, we will:
(1) Translate enhanced screening assays for rare lipid and metabolic disorders from the research laboratory to the NHS metabolic laboratory.
(2) Integrate metabolomics with genomics for diagnosis of Syndromes Without A Name.
With further technological development, i.e., faster sample turn-around and lower cost, we aim to incorporate more lipidomic/metabolomic technology into the diagnostic pathways as well as considering its future application to newborn screening programmes, allowing asymptomatic patients to be identified and diagnosed. The node will be open to new members who bring in different "omic" expertise including bioinformaticians and economists, also to new clinical centres with the challenge of diagnosing patients with rare metabolic disorders.
Organisations
- Swansea University (Lead Research Organisation)
- National Institute for Health Research (Co-funder)
- UNIVERSITY OF OXFORD (Collaboration)
- University College London (Collaboration)
- University of Manchester (Collaboration)
- University Hospital of Wales (Collaboration, Project Partner)
- National University of Singapore (Collaboration)
- Sheffield Children's NHS Foundation Trust (Collaboration)
- Shimadzu UK Ltd (Project Partner)
- SCIEX (Project Partner)
- Waters Corporation (Project Partner)
Publications
![publication icon](/resources/img/placeholder-60x60.png)
Griffiths W
(2023)
Role of Bile Acid Pathway Intermediates in Pathology of CTX
![publication icon](/resources/img/placeholder-60x60.png)
Griffiths W
(2023)
Role of Bile Acid Pathway Intermediates in Pathology of CTX
![publication icon](/resources/img/placeholder-60x60.png)
Griffiths WJ
(2023)
Role of Bile Acid Pathway Intermediates in Pathology of CTX
Description | Department of Health workshop on non-genetic conditions |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
Description | NHS Wales Rare Diseases Implementation Group |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Bile Acid Ring Trial |
Organisation | National University of Singapore |
Country | Singapore |
Sector | Academic/University |
PI Contribution | We are one of a number of groups world wide providing bile acid measurement on a standard reference material. |
Collaborator Contribution | We are one of a number of groups world wide providing bile acid measurement on a standard reference material. Commercial partners are providing authentic standards free of charge. |
Impact | An expert protocol has been developed for bile acid analysis in human plasma. |
Start Year | 2020 |
Description | Cardiff University & UHW |
Organisation | University Hospital of Wales |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | We have provided expertise, intellectual input and access to equipment to assist in the diagnosis of rare diseases. |
Collaborator Contribution | Our collaborators have provided access to appropriate samples and clinical expertise. |
Impact | We have assisted in patient diagnosis where genomic data was equivocal. |
Start Year | 2023 |
Description | ICH: Inborn errors of metabolism |
Organisation | University College London |
Department | Institute of Child Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Investigation of inborn errors of cholesterol biosynthesis and metabolism. |
Collaborator Contribution | Clinical information concerning inborn errors of metabolism |
Impact | Four publications |
Start Year | 2009 |
Description | Manchester: Collaboration on inborn errors of metabolism |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Analysis of plasma and urine samples in the study of inborn errors of cholesterol biosynthesis and metabolism. |
Collaborator Contribution | Provision of samples for the study of inborn errors of cholesterol biosynthesis and metabolism. |
Impact | doi: 10.1016/j.freeradbiomed.2019.04.020 doi: 10.1194/jlr.D083246 doi: 10.1016/j.jsbmb.2020.105794 doi: 10.1016/j.jsbmb.2016.03.018 doi: 10.1373/clinchem.2014.231332 doi: 10.1172/JCI68506 doi: 10.1016/j.freeradbiomed.2012.07.027 Multidisciplinary, medicine and analytical science. |
Start Year | 2012 |
Description | SHEFFIELD CHILDREN'S NHS FOUNDATION TRUST |
Organisation | Sheffield Children's NHS Foundation Trust |
Country | United Kingdom |
Sector | Public |
PI Contribution | Collaboration to facilitate the diagnosis of rare disease |
Collaborator Contribution | Facilitate the collection of relevant samples, provide background information and clinical information. |
Impact | The collaboration has assisted in clinical diagnosis where genetics were equivocal. |
Start Year | 2023 |
Description | Wellcome Centre for Human Genetics |
Organisation | University of Oxford |
Department | Oxford Hub |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are performing sterol analysis to clarify the biochemistry behind rare mutations in human and in a mouse model. |
Collaborator Contribution | Oxford are providing biological material. |
Impact | Grant application. |
Start Year | 2022 |
Description | Cardiff Huntington's Disease Centre Public Engagement Event |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Presentation to the Cardiff Huntington's Disease Centre Public Engagement Event. Great interest from the patients and carers about the work we are doing to support future clinical trials. |
Year(s) Of Engagement Activity | 2023 |
Description | DHSC |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation made to DHSC workshop on non-genetic conditions and how to address some of the barriers to improved outcomes and experience. |
Year(s) Of Engagement Activity | 2023 |
Description | Minister for Health and Social Services |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Press release describing Swansea Universities involvement in the UK Rare Disease Research Platform as the Lipidomics and metabolomics for rare disease diagnosis node. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.swansea.ac.uk/press-office/news-events/news/2023/12/swansea-university-opens-specialist-... |
Description | NHS WALES RDID |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Invited presentation to NHS Wales Rare Diseases Implementation Group. The presentation made the group aware of the potential of metabolomics/lipidomics for rare disease diagnosis. |
Year(s) Of Engagement Activity | 2023 |
Description | RAREsummit23 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Panellist in the session "DIAGNOSTIC ADVANCES: BEYOND THE GENOME" at the beginning of the meeting. Sparked an interest in the concept of using metabolomics/lipidomics to diagnose rare diseases. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.youtube.com/watch?v=KsZ4PvELAec |
Description | Welsh Government Visit |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Policymakers/politicians |
Results and Impact | Eluned Morgan AS/MS, Minister for Health and Social Services Welsh Government visited our laboratories to learn more about how metabolomics/lipidomics can be used in the diagnosis of rare diseases. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.swansea.ac.uk/press-office/news-events/news/2023/12/swansea-university-opens-specialist-... |