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Metabolomics and proteomics: insight into the disease

The importance of understanding the mechanism of disease cannot be underestimated, and looking into the mechanism from different research angles is always beneficial. We want to bring to your attention the study “Multi-omic profiling of plasma reveals molecular alterations in children with COVID-19”, where authors not only look into the mechanism and pathogenesis of the disease in children, but compare the data with previously published metabolomics and proteomics results in adults study.

Metabolomics and proteomics: insight into the disease

Dr. Wang and co-authors performed plasma proteomics and metabolomics in children with COVID-19 (n=18) and negative control cohort (n=12). Data provided new insights on the mechanism and pathogenesis of disease. The differentially expressed metabolites (DEM) and differentially expressed proteins could serve as potential therapeutic agents of COVID-19. Results were compared to the previously published similar study in adults with diseased cohort of 34 patients compared to negative control of 10.

A total of 1171 metabolites were identified, and 416 DEMs were detected. Blood coagulation-related processes were highly enriched at the proteomic level, while anabolism-related pathways involved in amino acid biosynthesis were enriched in the metabolic level. More DEMs were down-regulated in diseased group, indicating a generally suppressive effect of biological processes in kids with infection.

Metabolomics and proteomics: insight into the disease

Image above is showing Volcano plots with metabolic alterations between children with and without disease, as well as COVID-19 kids and COVID-19 adults. MMA – methylmalonic acid; DHOA – dihydroorotic acid; IAAID – indoleacetaldehyde; TRP – tryptophan

Five metabolites (all can be found in foods) were highly up-regulated in COVID-19-children compared to healthy. Dihydroorotic acid is a derivative of vitamin B13 or orotic acid that exists in bovine milk and dairy products; tryptophan is highly expressed in meats. Mannitol (essential in energy reserves and osmoregulation) is commonly found in vegetables (i.e., celery and leek). Elevated levels of methylmalonic acid and homocysteine in serum are indicators of vitamin B12 deficiency. However, no children underwent a special diet or had vitamin B12 deficiency, and homocysteine was not differentially expressed in COVID-19-children against healthy children in our plasma metabolomic data. So, the changes might be attributed to the infection, but not the diet. The prioritized 5 metabolites inhibited the expression of pro-inflammatory factors, and two of them, methylmalonic acid and mannitol, also suppressed coronaviral replication, implying a protective role of these metabolites in COVID-19-children.

Metabolomics and proteomics: insight into the disease

The authors used the annotations of Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and performed functional enrichment analyses for proteins and metabolites. It was found that a considerable number of biological processes and metabolic pathways enriched in COVID-19-children against COVID-19-adults or healthy children were overlapped, such as platelet degranulation, blood coagulation, fibrinolysis and plasminogen activation in the proteomic level, and ABC transporters, biosynthesis of amino acids and pyrimidine metabolism in the metabolic level. Although most of these processes/pathways were also enriched in the blood samples of COVID-19-adults, they were altered to a much stronger extent in COVID-19-children.

We offer TM Widely-Targeted Metabolomics method for studying plasma metabolites in human and animal samples.


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