ArticleMolecular systems biology2012
Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation.
Article in Molecular systems biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed.
- Evaluating transcriptomic integration for cyanobacterial constraint-based metabolic modelling.Frontiers in bioinformatics · 2026Article
- A streamlined and comprehensive protocol for the generation and multi-omic analysis of human monocyte-derived macrophages.BMC biotechnology · 2025Article
- Role of amino acid metabolism in osteoporosis: Effects on the bone microenvironment and treatment strategies (Review).Molecular medicine reports · 2025Review
- Investigative needle core biopsies support multimodal deep-data generation in glioblastoma.Nature communications · 2025Article
- Genome-scale models in human metabologenomics.Nature reviews. Genetics · 2025Review
- Navigating Cancer Complexity: Integrative Multi-Omics Methodologies for Clinical Insights.Clinical Medicine Insights. Oncology · 2025Review
- Article
- Optimizing MS-Based Multi-Omics: Comparative Analysis of Protein, Metabolite, and Lipid Extraction Techniques.Metabolites · 2024Article
- Inferring secretory and metabolic pathway activity from omic data with secCellFie.Metabolic engineering · 2024Article
- State-of the-Art Constraint-Based Modeling of Microbial Metabolism: From Basics to Context-Specific Models with a Focus on Methanotrophs.Microorganisms · 2023Review
- An integrated systems biology approach reveals differences in formate metabolism in the genusiScience · 2023Article
- Genome-scale modeling predicts metabolic differences between macrophage subtypes in colorectal cancer.iScience · 2023Article
- Integrating Omics Data in Genome-Scale Metabolic Modeling: A Methodological Perspective for Precision Medicine.Metabolites · 2023Review
- A Multi-Level Systems Biology Analysis of Aldrin's Metabolic Effects on Prostate Cancer Cells.Proteomes · 2023Article
- Ensemble-based genome-scale modeling predicts metabolic differences between macrophage subtypes in colorectal cancer.bioRxiv : the preprint server for biology · 2023Article
- Context-Specific Genome-Scale Metabolic Modelling and Its Application to the Analysis of COVID-19 Metabolic Signatures.Metabolites · 2023Review
- Targeted Enzymatic VLP-Nanoreactors with β-Glucocerebrosidase Activity as Potential Enzyme Replacement Therapy for Gaucher's Disease.ChemMedChem · 2022Article
- Quantitative modeling of human liver reveals dysregulation of glycosphingolipid pathways in nonalcoholic fatty liver disease.iScience · 2022Article
- Review of Current Human Genome-Scale Metabolic Models for Brain Cancer and Neurodegenerative Diseases.Cells · 2022Review
- Systems-based approaches to study immunometabolism.Cellular & molecular immunology · 2022Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Macrophages are central players in immune response, manifesting divergent phenotypes to control inflammation and innate immunity through release of cytokines and other signaling factors. Recently, the focus on metabolism has been reemphasized as critical signaling and regulatory pathways of human pathophysiology, ranging from cancer to aging, often converge on metabolic responses. Here, we used genome-scale modeling and multi-omics (transcriptomics, proteomics, and metabolomics) analysis to assess metabolic features that are critical for macrophage activation. We constructed a genome-scale metabolic network for the RAW 264.7 cell line to determine metabolic modulators of activation. Metabolites well-known to be associated with immunoactivation (glucose and arginine) and immunosuppression (tryptophan and vitamin D3) were among the most critical effectors. Intracellular metabolic mechanisms were assessed, identifying a suppressive role for de-novo nucleotide synthesis. Finally, underlying metabolic mechanisms of macrophage activation are identified by analyzing multi-omic data obtained from LPS-stimulated RAW cells in the context of our flux-based predictions. Our study demonstrates metabolism's role in regulating activation may be greater than previously anticipated and elucidates underlying connections between activation and metabolic effectors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.