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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

The identification of metabolomic biomarkers relies on the analysis of large cohorts of patients compared to healthy controls followed by the validation of markers in an independent sample set. Indeed, circulating biomarkers should be causally linked to pathology to ensure that changes in the marker precede changes in the disease. However, this approach becomes unfeasible in rare diseases due to the paucity of samples, necessitating the development of new methods for biomarker identification. The present study describes a novel approach that combines samples from both mouse models and human patients to identify biomarkers of OPMD. We initially identified a pathology-specific metabolic fingerprint in murine dystrophic muscle. This metabolic fingerprint was then translated into (paired) murine serum samples and then to human plasma samples. This study identified a panel of nine candidate biomarkers that could predict muscle pathology with a sensitivity of 74.3% and specificity of 100% in a random forest model. These findings demonstrate that the proposed approach can identify biomarkers with good predictive performance and a higher degree of confidence in their relevance to pathology than markers identified in a small cohort of human samples alone. Therefore, this approach has a high potential utility for identifying circulating biomarkers in rare diseases.

Details

Title
Novel Metabolomic Approach for Identifying Pathology-Specific Biomarkers in Rare Diseases: A Case Study in Oculopharyngeal Muscular Dystrophy (OPMD)
Author
Pradeep Harish 1   VIAFID ORCID Logo  ; Malerba, Alberto 2 ; Rosemarie H M J M Kroon 3   VIAFID ORCID Logo  ; Shademan, Milad 4 ; Baziel van Engelan 3 ; Raz, Vered 4   VIAFID ORCID Logo  ; Popplewell, Linda 5 ; Snowden, Stuart G 2 

 Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, UK 
 Department of Biological Sciences, Royal Holloway University of London, Egham TW20 0EX, Surrey, UK 
 Department of Rehabilitation, Donder Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, 6525 AJ Nijmegen, The Netherlands 
 Department of Human Genetics, Leiden University Medical Centre, 2333 ZC Leiden, The Netherlands 
 Department of Biological Sciences, Royal Holloway University of London, Egham TW20 0EX, Surrey, UK; National Horizons Centre, Teesside University, Darlington DL1 1HG, County Durham, UK 
First page
769
Publication year
2023
Publication date
2023
Publisher
MDPI AG
e-ISSN
22181989
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2829836507
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.