The complexome contextualizes proteomics data to fingerprint biological states and highlight perturbed functional modules in disease

ABSTRACT: Proteins organize into functional assemblies that drive diverse biological activities. Leveraging a comprehensive dataset of manually curated annotations for the human protein complexome, we investigated biological perturbations at the protein complex level. Using proteomics and transcriptomics data from fibroblasts of patients with inborn errors of metabolism (IEM) and control samples, we globally mapped information onto complex subunits to discern affected processes. Across the patient cohort, mitochondrial oxidative phosphorylation emerged as the most perturbed pathway, identified through proteomics datasets. Simultaneously, metabolomics measurements highlighted significant regulation of phospholipids in patients with Fatty Acid and Mitochondrial IEM. Notably, proteomics analysis revealed the regulation of protein complexes involved in histone (de)acetylation, a finding validated through Western Blot analysis measuring histone acetylation levels. This introduces a novel epigenetic dimension to IEM and metabolic research, suggesting avenues for further exploration. Our study demonstrates a multiomics integration concept by mapping proteomics and transcriptomics onto model organism complexomes. This integrative approach extends to metabolomics and lipidomics, associating information with complexes having metabolic functions, such as enzymatic complexes. This global strategy for identifying disease-relevant perturbations offers a systems-wide perspective on molecular-level physiological and pathological changes. Such insights are crucial for devising clinical intervention strategies and prioritizing druggable pathways and complexes. The presented methodology provides a foundation for future investigations, emphasizing the importance of integrating various omics data to comprehensively understand cellular machinery alterations and facilitate targeted therapeutic approaches.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Fibroblast

DISEASE(S): Lipid Metabolism Disorder,Mitochondrial Complex I Deficiency,Organic Acidemia

SUBMITTER: Teresa Mendes Maia  

LAB HEAD: Simon Devos

PROVIDER: PXD048352 | Pride | 2026-09-14

REPOSITORIES: Pride