ArticlePLoS computational biology2021
A multi-approach and multi-scale platform to model CD4+ T cells responding to infections.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Recent applications of quantitative systems pharmacology and machine learning models across diseases.Journal of pharmacokinetics and pharmacodynamics · 2022Pooled it
- Improvement in model flexibility reveals signaling pathway in T cell responses to pulsatile stimuli.NPJ systems biology and applications · 2026Article
- A comprehensive mechanistic multicellular model of the human immune system spanning 11 diseases.Frontiers in immunology · 2026Article
- Physical Activity Guidelines for Astronauts: An Immunological Perspective.Biomolecules · 2025Review
- Mechanistic modeling of cell viability assays with in silico lineage tracing.PLoS computational biology · 2025Article
- Distinguishing multiple roles of T cell and macrophage involvement in determining lymph node fates during Mycobacterium tuberculosis infection.PLoS computational biology · 2025Article
- The dawn of biophysical representations in computational immunology.QRB discovery · 2025Review
- Multicellular model of neuroblastoma proposes unconventional therapy based on multiple roles of p53.PLoS computational biology · 2024Article
- Using In silico models to predict lymphocyte activation and development in a data rich era.Immunoinformatics (Amsterdam, Netherlands) · 2024Article
- Perspectives on computational modeling of biological systems and the significance of the SysMod community.Bioinformatics advances · 2024Article
- Modeling and Remodeling the Cell: How Digital Twins and HCMV Can Elucidate the Complex Interactions of Viral Latency, Epigenetic Regulation, and Immune Responses.Current clinical microbiology reports · 2023Article
- From time-series transcriptomics to gene regulatory networks: A review on inference methods.PLoS computational biology · 2023Review
- A multiscale mechanistic model of human dendritic cells forFrontiers in immunology · 2023Article
- T cell phenotype switching in autoimmune disorders: Clinical significance of targeting metabolism.Clinical and translational medicine · 2022Article
- Building digital twins of the human immune system: toward a roadmap.NPJ digital medicine · 2022Review
- Mathematical Modeling of Proliferative Immune Response Initiated by Interactions Between Classical Antigen-Presenting Cells Under Joint Antagonistic IL-2 and IL-4 Signaling.Frontiers in molecular biosciences · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Immune responses rely on a complex adaptive system in which the body and infections interact at multiple scales and in different compartments. We developed a modular model of CD4+ T cells, which uses four modeling approaches to integrate processes at three spatial scales in different tissues. In each cell, signal transduction and gene regulation are described by a logical model, metabolism by constraint-based models. Cell population dynamics are described by an agent-based model and systemic cytokine concentrations by ordinary differential equations. A Monte Carlo simulation algorithm allows information to flow efficiently between the four modules by separating the time scales. Such modularity improves computational performance and versatility and facilitates data integration. We validated our technology by reproducing known experimental results, including differentiation patterns of CD4+ T cells triggered by different combinations of cytokines, metabolic regulation by IL2 in these cells, and their response to influenza infection. In doing so, we added multi-scale insights to single-scale studies and demonstrated its predictive power by discovering switch-like and oscillatory behaviors of CD4+ T cells that arise from nonlinear dynamics interwoven across three scales. We identified the inflamed lymph node's ability to retain naive CD4+ T cells as a key mechanism in generating these emergent behaviors. We envision our model and the generic framework encompassing it to serve as a tool for understanding cellular and molecular immunological problems through the lens of systems immunology.
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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.