Integrating Genome-Scale Metabolic Models with Patient Plasma Metabolome to Study Endothelial Metabolism In Situ

Research output: Contribution to journalJournal articleResearchpeer-review

Documents

  • Fulltext

    Final published version, 3.21 MB, PDF document

Patient blood samples are invaluable in clinical omics databases, yet current methodologies often fail to fully uncover the molecular mechanisms driving patient pathology. While genome-scale metabolic models (GEMs) show promise in systems medicine by integrating various omics data, having only exometabolomic data remains a limiting factor. To address this gap, we introduce a comprehensive pipeline integrating GEMs with patient plasma metabolome. This pipeline constructs case-specific GEMs using literature-based and patient-specific metabolomic data. Novel computational methods, including adaptive sampling and an in-house developed algorithm for the rational exploration of the sampled space of solutions, enhance integration accuracy while improving computational performance. Model characterization involves task analysis in combination with clustering methods to identify critical cellular functions. The new pipeline was applied to a cohort of trauma patients to investigate shock-induced endotheliopathy using patient plasma metabolome data. By analyzing endothelial cell metabolism comprehensively, the pipeline identified critical therapeutic targets and biomarkers that can potentially contribute to the development of therapeutic strategies. Our study demonstrates the efficacy of integrating patient plasma metabolome data into computational models to analyze endothelial cell metabolism in disease contexts. This approach offers a deeper understanding of metabolic dysregulations and provides insights into diseases with metabolic components and potential treatments.

Original languageEnglish
Article number5406
JournalInternational Journal of Molecular Sciences
Volume25
Issue number10
Number of pages22
ISSN1661-6596
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

    Research areas

  • endothelial cell metabolism, exo-metabolomics integration, genome-scale metabolic models, metabolic network analysis, sampling algorithms

ID: 393596875