Metabolomics bridging proteomics along metabolites/oncometabolites and protein modifications: paving the way toward integrative multiomics

Abstract Systems biology adopted functional and integrative multiomics approaches enable to discover the whole set of interacting regulatory components such as genes, transcripts, proteins, metabolites, and metabolite dependent protein modifications. This interactome build up the midpoint of protein-protein/PTM, protein-DNA/RNA, and protein-metabolite network in a cell. As the key drivers in cellular metabolism, metabolites are precursors and regulators of protein post-translational modifications [PTMs] that affect protein diversity and functionality. The precisely orchestrated core pattern of metabolic networks refer to paradigm ‘metabolites regulate PTMs, PTMs regulate enzymes, and enzymes modulate metabolites’ through a multitude of feedback and feed-forward pathway loops. The concept represents a flawless PTM-metabolite-enzyme(protein) regulomics underlined in reprogramming cancer metabolism. Immense interconnectivity of those biomolecules in their spectacular network of intertwined metabolic pathways makes integrated proteomics and metabolomics an excellent opportunity, and the central component of integrative multiomics framework. It will therefore be of significant interest to integrate global proteome and PTM-based proteomics with metabolomics to achieve disease related altered levels of those molecules. Thereby, present update aims to highlight role and analysis of interacting metabolites/oncometabolites, and metabolite–regulated PTMs loop which may function as translational monitoring biomarkers along the reprogramming continuum of oncometabolism.