Puniya2021 - Naive CD4+ T cell metabolic model

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CD4+ T cells are critical components in the human immune system. They produce cytokines to fight against pathogens and abnormal cells and stimulate other cells, such as B cells, macrophages, and neutrophils, to generate an immune response. Naive CD4+ T cells are precursor cells that can differentiate into T helper - 1, - 2, - 17 (Th1, Th2, Th17) and regulatory T cells (Tregs) subtypes based on the type of pathogens or disease. The naive CD4+ T cell model consists of 5179 reactions, 3153 metabolites, and 1055 genes. Together with Th1, Th2, and Th17 models, the naive CD4+ T cell model helped identify drug targets and repurposable drugs against autoimmune diseases.
Related Publication
  • Integrative computational approach identifies drug targets in CD4+ T-cell-mediated immune disorders
  • Bhanwar Lal Puniya, Rada Amin, Bailee Lichter, Robert Moore, Alex Ciurej, Sydney J. Bennett, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar
  • NPJ Systems Biology and Applications , 1/ 2021 , DOI: 10.1038/s41540-020-00165-3
  • Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, USA. Systems Biology, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK. Centre for Mathematical and Computational Biology, CMCB, University of Surrey, Guildford, UK. Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
  • CD4+ T cells provide adaptive immunity against pathogens and abnormal cells, and they are also associated with various immune-related diseases. CD4+ T cells’ metabolism is dysregulated in these pathologies and represents an opportunity for drug discovery and development. Genome-scale metabolic modeling offers an opportunity to accelerate drug discovery by providing high-quality information about possible target space in the context of a modeled disease. Here, we develop genome-scale models of naïve, Th1, Th2, and Th17 CD4+ T-cell subtypes to map metabolic perturbations in rheumatoid arthritis, multiple sclerosis, and primary biliary cholangitis. We subjected these models to in silico simulations for drug response analysis of existing FDA-approved drugs and compounds. Integration of disease-specific differentially expressed genes with altered reactions in response to metabolic perturbations identified 68 drug targets for the three autoimmune diseases. In vitro experimental validation, together with literature-based evidence, showed that modulation of fifty percent of identified drug targets suppressed CD4+ T cells, further increasing their potential impact as therapeutic interventions. Our approach can be generalized in the context of other diseases, and the metabolic models can be further used to dissect CD4+ T-cell metabolism.
Submitter of the first revision: Bhanwar Lal Puniya
Submitter of this revision: Mikal Daou
Modellers: Bhanwar Lal Puniya, Mikal Daou

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Mathematical Modelling Ontology Constraint-based model

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Model files

TNM1055.xml SBML L3V1 representation of human naive CD4+ T cell metabolism model. 8.91 MB Preview | Download

Additional files

FROG_TNM1055.zip FROG report of TNM1055 56.05 KB Preview | Download
Memote_TNM1055.pdf Memote 1.13 MB Preview | Download
TNM1055.fbc2.xml FBC v2 representation of TNM1055 9.07 MB Preview | Download
miniFROG_TNM1055_Tnaive.xlsx miniFROG report of TNM1055 29.78 KB Preview | Download

  • Model originally submitted by : Bhanwar Lal Puniya
  • Submitted: Jan 23, 2021 8:38:22 PM
  • Last Modified: Jun 21, 2022 11:25:41 AM
  • Version: 6 public model Download this version
    • Submitted on: Jun 21, 2022 11:25:41 AM
    • Submitted by: Mikal Daou
    • With comment: Model revised without commit message
  • Version: 5 public model Download this version
    • Submitted on: Jun 11, 2022 12:13:47 AM
    • Submitted by: Bhanwar Lal Puniya
    • With comment: Added FROG report and miniFROG report
  • Version: 4 public model Download this version
    • Submitted on: Jan 23, 2021 8:38:22 PM
    • Submitted by: Bhanwar Lal Puniya
    • With comment: Edited model metadata online.

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