Proteomics and Metabolomics

Proteomics and metabolomics are complementary disciplines that characterise the protein and small‐molecule constituents of biological systems. Proteomics employs high‐resolution mass spectrometry to identify and quantify the full complement of proteins—both in terms of abundance and post‐translational modification—revealing functional networks and dynamic responses to stimuli. Metabolomics utilises similar technologies, often coupled with chromatographic separation, to profile hundreds to thousands of low–molecular‐weight metabolites in biofluids or tissues, thereby providing a “snapshot” of cellular biochemical activity. Together, these approaches link gene expression to phenotype by mapping enzymes, substrates and products across metabolic and signalling pathways. Advances in quantitative workflows, bioinformatic integration and multi‐omic network analysis have transformed our ability to dissect disease mechanisms, discover diagnostic biomarkers and monitor therapeutic response with unprecedented depth and precision.

Research from Nature Portfolio

Ozone‐enabled fatty acid discovery has expanded the known diversity of unsaturated plasma lipids by coupling gas‐phase cleavages of carbon–carbon double bonds with liquid chromatography–mass spectrometry, identifying previously masked isomers and revealing non‐canonical double‐bond positions across a dynamic range spanning five orders of magnitude. A separate longitudinal lipidomics study of over 1,500 plasma samples from 112 individuals collected over several years uncovered dynamic alterations in triacylglycerols, ether‐linked phosphatidylethanolamines, lysophospholipids, cholesterol esters and ceramides during viral infection, insulin resistance and ageing, and delineated cytokine–lipidome networks that correlate with immune homeostasis and metabolic trajectories. More recently, longitudinal plasma proteomics of 318 hospitalised COVID‐19 patients profiled 6,385 proteins to identify early admission biomarkers that predict progression to critical illness; these proteins implicate pathways of extracellular matrix turnover, cellular adhesion and tissue remodelling and were attenuated by tyrosine kinase inhibition, offering both prognostic insight and therapeutic leads.

Research from all publishers

A targeted metabolomics approach in patients with sepsis‐induced acute respiratory distress syndrome (ARDS) delineated distinct lipid signatures—particularly lysophosphatidylethanolamine plasmalogens and phosphatidylcholines—that distinguish direct from indirect ARDS and non‐ARDS controls, implicating glycerophospholipid and sphingolipid metabolism in lung injury biology. Integrative analysis combining untargeted metabolomics with proteomics in septic shock patients revealed widespread dysregulation of amino acid metabolism—especially in phenylalanine, tyrosine and tryptophan pathways—and linked these perturbations to inflammation and organ dysfunction, identifying hub metabolites with high prognostic accuracy. In the field of precision nutrition, a recent review highlighted how metabolomics‐derived “metabotypes” and combined predictor models can capture individual dietary exposures, genetic variation and metabolic responses, offering a path to tailored dietary recommendations and improved prevention of cardiometabolic disease.

Proteomics and Metabolomics publication trend

The graph below shows the total number of articles in proteomics and metabolomics across all publications each year (not limited to Nature Index journals).

Technical terms

Proteomics: Large‐scale identification and quantification of proteins in a biological sample, including their modifications and interactions.

Metabolomics: Comprehensive analysis of small‐molecule metabolites (e.g., amino acids, lipids, sugars) to characterise biochemical states of cells or organisms.

Mass spectrometry (MS): Analytical technique that measures mass‐to‐charge ratios of ionised molecules, enabling their identification and quantification.

Liquid chromatography–mass spectrometry (LC–MS): Method combining chromatographic separation with mass spectrometric detection, used extensively in proteomic and metabolomic profiling.

Glycerophospholipids: Major class of membrane phospholipids involved in cell structure and signal transduction, often quantified in lipidomics.

Biomarker: A measurable molecule whose presence, absence or quantity indicates a biological or pathological condition, used for diagnosis or monitoring.

References

1. Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome. Nature Communications (2023).
2. Dynamic lipidome alterations associated with human health, disease and ageing. Nature Metabolism (2023).
3. Longitudinal plasma proteomics reveals biomarkers of alveolar-capillary barrier disruption in critically ill COVID-19 patients. Nature Communications (2024).
4. A targeted metabolomics approach for sepsis-induced ARDS and its subphenotypes. Critical Care (2023).
5. Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis. Journal of Translational Medicine (2022).
6. Role of metabolomics in the delivery of precision nutrition. Redox Biology (2023).