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Review
. 2024 Apr 3;14(4):200.
doi: 10.3390/metabo14040200.

Challenges in the Metabolomics-Based Biomarker Validation Pipeline

Shenghan Li  1   2   3 , Nikita Looby  1   3   4 , Vinod Chandran  1   2   3   5   6 , Vathany Kulasingam  2   7
Affiliations
Review

Challenges in the Metabolomics-Based Biomarker Validation Pipeline

Shenghan Li et al. Metabolites. .

Abstract

As end-products of the intersection between the genome and environmental influences, metabolites represent a promising approach to the discovery of novel biomarkers for diseases. However, many potential biomarker candidates identified by metabolomics studies fail to progress beyond analytical validation for routine implementation in clinics. Awareness of the challenges present can facilitate the development and advancement of innovative strategies that allow improved and more efficient applications of metabolite-based markers in clinical settings. This minireview provides a comprehensive summary of the pre-analytical factors, required analytical validation studies, and kit development challenges that must be resolved before the successful translation of novel metabolite biomarkers originating from research. We discuss the necessity for strict protocols for sample collection, storage, and the regulatory requirements to be fulfilled for a bioanalytical method to be considered as analytically validated. We focus especially on the blood as a biological matrix and liquid chromatography coupled with tandem mass spectrometry as the analytical platform for biomarker validation. Furthermore, we examine the challenges of developing a commercially viable metabolomics kit for distribution. To bridge the gap between the research lab and clinical implementation and utility of relevant metabolites, the understanding of the translational challenges for a biomarker panel is crucial for more efficient development of metabolomics-based precision medicine.

Keywords: analytical validation; biomarker; kit development; metabolomics; pre-analytical factors; regulatory guideline.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Summary of challenges within a LC-MS-based metabolomics biomarker validation pipeline.
Figure 2
Figure 2
Analytical parameters that must be validated according to International Council for Harmonisation for bioanalytical methods. Colors underlining each parameter correspond to wheel color.
See this image and copyright information in PMC

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