Toward a Standardized Strategy of Clinical Metabolomics for the Advancement of Precision Medicine

Abstract

Despite the tremendous success, pitfalls have been observed in every step of a clinical metabolomics workflow, which impedes the internal validity of the study. Furthermore, the demand for logistics, instrumentations, and computational resources for metabolic phenotyping studies has far exceeded our expectations. In this conceptual review, we will cover inclusive barriers of a metabolomics-based clinical study and suggest potential solutions in the hope of enhancing study robustness, usability, and transferability. The importance of quality assurance and quality control procedures is discussed, followed by a practical rule containing five phases, including two additional “pre-pre-” and “post-post-” analytical steps. Besides, we will elucidate the potential involvement of machine learning and demonstrate that the need for automated data mining algorithms to improve the quality of future research is undeniable. Consequently, we propose a comprehensive metabolomics framework, along with an appropriate checklist refined from current guidelines and our previously published assessment, in the attempt to accurately translate achievements in metabolomics into clinical and epidemiological research. Furthermore, the integration of multifaceted multi-omics approaches with metabolomics as the pillar member is in urgent need. When combining with other social or nutritional factors, we can gather complete omics profiles for a particular disease. Our discussion reflects the current obstacles and potential solutions toward the progressing trend of utilizing metabolomics in clinical research to create the next-generation healthcare system.

Analysis of biomarkers and metabolic pathways in patients with unstable angina based on ultra‑high‑performance liquid chromatography‑quadrupole time‑of‑flight mass spectrometry

“…elucidating differences between healthy and diseased states Analysis of biomarkers and metabolic pathways in patients with unstable angina based on ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry unstable angina, urine, metabolomics, ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, biomarkers is of important clinical use (10). Metabolomics techniques aim to quantitatively measure the systemic effects of endogenous small molecule metabolites produced by exogenous substances in the body (11,12). additionally, it elucidates pathological processes and the dynamic metabolic responses of substances in the body (13).…”

“…Elucidating differences between healthy and diseased states is of important clinical use ( 10 ). Metabolomics techniques aim to quantitatively measure the systemic effects of endogenous small molecule metabolites produced by exogenous substances in the body ( 11 , 12 ). Additionally, it elucidates pathological processes and the dynamic metabolic responses of substances in the body ( 13 ).…”

Metabolomic Approaches to Study Chemical Exposure-Related Metabolism Alterations in Mammalian Cell Cultures

“…The same batches of chemicals and consumables are to be used for all samples, and sample handling should be carefully randomized across different sample classes (for the date of sample preparation, sample collection, chemical analysis, etc.) [ 100 , 101 ].…”

Integrative Metabolomics to Identify Molecular Signatures of Responses to Vaccines and Infections

“…Identification of disease phenotypes or vaccine efficacy markers using metabolomics has the advantage of not requiring elaborate amplification of nucleotides or protein digestion [6]. Assays that detect specific metabolites such as eicosanoid, arginine, and citrulline testing are currently employed for clinical use after being associated with immune regulatory pathways [26][27][28] as well as metabolic diseases [29][30][31]. Metabolite tests that are first week of human life [34].…”

“…infectious disease states or vaccine immunogenicity based on reproducible metabolic signatures that reflect specific discernible phenotypes, and can be used as a consistent readout [7]. For all its many strengths, the field of metabolomics is lagging behind other omics fields in terms of standardization of protocols [31] and routine usage of repositories for mass spectrometry data [85].…”