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Model-driven analysis of metabolic immunomodulators of macrophage activation

ABSTRACT: Model-driven multi-omic data analysis of the RAW 264.7 cell line elucidates metabolic immunomodulators of macrophage activation

OTHER RELATED OMICS DATASETS IN: PRJNA171843MTBLS23PRJNA152753

INSTRUMENT(S): LTQ Orbitrap, LTQ

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Raw-264.7 Cell

SUBMITTER: Matthew Monroe

LAB HEAD: Bernard Palsson

PROVIDER: PXD003055 | Pride | 2015-11-11

REPOSITORIES: Pride

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			Action	DRS
	SBEP_C1_LPS_001_R1_29Oct10_Falcon_10-10-03.mgf	Mgf
	SBEP_C1_LPS_001_R1_29Oct10_Falcon_10-10-03.pride.mgf.gz	Mgf
	SBEP_C1_LPS_001_R1_29Oct10_Falcon_10-10-03.raw	Raw
	SBEP_C1_LPS_001_R1_29Oct10_Falcon_10-10-03_Job1238114_msgfplus.mzid.gz	Mzid
	SBEP_C1_LPS_001_R1_29Oct10_Falcon_10-10-03_Job1238114_msgfplus.pride.mztab.gz	Mztab

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Publications

Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation.

Bordbar Aarash A Mo Monica L ML Nakayasu Ernesto S ES Schrimpe-Rutledge Alexandra C AC Kim Young-Mo YM Metz Thomas O TO Jones Marcus B MB Frank Bryan C BC Smith Richard D RD Peterson Scott N SN Hyduke Daniel R DR Adkins Joshua N JN Palsson Bernhard O BO

Molecular systems biology 20120626

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 asse ...[more]

PMID: 22735334

Similar Datasets

Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation

Project description: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. Two condition (flagellin and LPS) time course exposure of RAW 264.7 cell line at 1, 2, 4, and 24 hours. Two replicates for each condition and time point. All conditions compared to a pool of untreated cells at a 0 hour time point.

2012-08-02 | E-GEOD-39785 | biostudies-arrayexpress

Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation

Project description: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. A genome-scale metabolic network for the RAW 264.7 cell line was constructed 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 were identified by analyzing multi-omic data obtained from LPS-stimulated RAW cells in the context of our flux-based predictions. This study demonstrates that the role of metabolism in regulating activation may be greater than previously anticipated and elucidates underlying connections between activation and metabolic effectors. This submission corresponds to the metabolomics data from this study.

2012-09-05 | MTBLS23 | MetaboLights

Quantitative Profiling of Protein S-Glutathionylation during Nanoparticle-Induced Oxidative Stress

Project description:Quantitative profiling of protein s-glutathionylation (SSG) reveals redox-dependent regulation of macrophage function during nanoparticle-induced oxidative stress

2016-08-02 | PXD003356 | Pride

Stochiometric Quantification of the Thiol Redox Proteome Reveals Subcellular Compartmentalization and Susceptibility to Oxidative Perturbations

Project description:Posttranslational modifications of protein cysteine thiols play a significant role in redox regulation and the pathogenesis of human diseases. However, the cellular redox landscape in terms of quantitative, site-specific occupancies of thiol modifications at the proteome level, especially under physiological conditions, is still largely uncharacterized. Herein, we report the site occupancies of both S-glutathionylation (SSG) and total reversible thiol oxidation (total oxidation) in RAW 264.7 macrophage cells under basal conditions. The occupancies of thiol modifications for ~4,000 cysteine sites were quantified, which revealed a mean site occupancy of 4.0% for SSG and 11.9% for total oxidation, respectively. Correlations between site occupancies and structural features such as pKa, relative residue surface accessibility, and hydrophobicity were observed. Proteome-wide site occupancy analysis also revealed a strong subcellular compartmentalization in thiol redox status, where the average occupancies of SSG and total oxidation in distinct compartments correlate well with the redox potentials of respective organelles.

2020-08-13 | PXD019913 | Pride

Daylight-driven carbon exchange through a vertically structured microbial community

Project description:Tracing autotroph and heterotroph photosynthetic catalytic carbon cycling within a microbial mat, confirming biomass 13C incorporation into extracellular polymeric substances through proteomics.

2023-07-20 | PXD012190 | Pride

Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation

2014-06-25 | ST000084 | MetabolomicsWorkbench

Mus musculus

Project description:Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation

| PRJNA171843 | ENA

Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation

2012-08-03 | GSE39785 | GEO

LPS treatment of RAW2647 macrophages

Project description:Macrophages are central players in the immune response and manifest divergent phenotypes to control inflammation and innate immunity. Signaling factors are traditionally recognized as the stimuli governing macrophage functions. In recent years, metabolism’s importance has been reemphasized as critical signaling and regulatory pathways of human diseases and processes, ranging from cancer to aging, often converge on metabolic responses. In this study, we assessed metabolic features that play critical roles in macrophage function. We constructed a genome-scale metabolic network for the RAW 264.7 cell line, an oft-used in vitro model. We determined immunomodulators of activation. Metabolites well-known to be associated with immunoactivation (e.g., glucose and arginine) and immunosuppression (e.g., tryptophan and vitamin D3) were amongst the most critical effectors. Intracellular metabolic mechanisms linked critical suppressive effectors were assessed, identifying a suppressive role for nucleotide synthesis. Furthermore, we demonstrate how metabolic mechanisms of macrophage activation can be identified by analyzing multi-omic data of LPS-stimulated RAW cells in the context of our predictions. Our study demonstrates metabolism’s role in regulating macrophage activation may be greater than previously anticipated. The RAW 264.7 (ATTC) cell line was stimulated for 24 hours with LPS. Treated cells were washed twice with Dulbecco’s PBS and harvested for high-throughput analyses. Labeled cDNA was prepared as described (Jones et al. 2010). A mixture Cy3-labeled control cDNA and Cy5-labeled were hybridized to Agilent Mouse GE 4x44K v2 Microarray (Agilent Technologies) and processed. Image analysis and intra-chip normalization were performed with Feature Extraction 9.5.3.1 (Agilent). Data were analyzed with MeV (tm4.org) or with custom python scripts

2012-01-24 | E-GEOD-35237 | biostudies-arrayexpress

Host targets of Citrobacter secreted effectors

Project description:Identification of human proteins targeted by Citrobacter secreted effectors by affinity purification followed by mass spectrometry.

2016-06-22 | PXD003943 | Pride

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