ArticlePLoS computational biology2011
A hybrid model of mammalian cell cycle regulation.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 100 citations in OpenAlex.
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- A comprehensive review of computational cell cycle models in guiding cancer treatment strategies.NPJ systems biology and applications · 2024Review
- Comparing the Efficacy of Two Generations of EGFR-TKIs: An Integrated Drug-Disease Mechanistic Model Approach in EGFR-Mutated Lung Adenocarcinoma.Biomedicines · 2024Article
- Reusable rule-based cell cycle model explains compartment-resolved dynamics of 16 observables in RPE-1 cells.PLoS computational biology · 2024Article
- Stability analysis of a multiscale model of cell cycle dynamics coupled with quiescent and proliferating cell populations.PloS one · 2023Article
- A continuous-time stochastic Boolean model provides a quantitative description of the budding yeast cell cycle.Scientific reports · 2022Article
- Hybrid modelling of biological systems: current progress and future prospects.Briefings in bioinformatics · 2022Review
- A mathematical model for cell cycle control: graded response or quantized response.Cell cycle (Georgetown, Tex.) · 2022Article
- Modeling Progression of Single Cell Populations Through the Cell Cycle as a Sequence of Switches.Frontiers in molecular biosciences · 2021Article
- Mathematical modelling of breast cancer cells in response to endocrine therapy and Cdk4/6 inhibition.Journal of the Royal Society, Interface · 2020Article
- A hybrid stochastic model of the budding yeast cell cycle.NPJ systems biology and applications · 2020Article
- Boolean model of anchorage dependence and contact inhibition points to coordinated inhibition but semi-independent induction of proliferation and migration.Computational and structural biotechnology journal · 2020Article
- A feedback loop of conditionally stable circuits drives the cell cycle from checkpoint to checkpoint.Scientific reports · 2019Article
- Systems biology: perspectives on multiscale modeling in research on endocrine-related cancers.Endocrine-related cancer · 2019Review
- Coordinated histone modifications and chromatin reorganization in a single cell revealed by FRET biosensors.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- A blueprint for human whole-cell modeling.Current opinion in systems biology · 2018Article
- Predicting network modules of cell cycle regulators using relative protein abundance statistics.BMC systems biology · 2017Article
- Modelling the molecular mechanisms of aging.Bioscience reports · 2017Review
- Quantitative Systems Biology to decipher design principles of a dynamic cell cycle network: the "Maximum Allowable mammalian Trade-Off-Weight" (MAmTOW).NPJ systems biology and applications · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The timing of DNA synthesis, mitosis and cell division is regulated by a complex network of biochemical reactions that control the activities of a family of cyclin-dependent kinases. The temporal dynamics of this reaction network is typically modeled by nonlinear differential equations describing the rates of the component reactions. This approach provides exquisite details about molecular regulatory processes but is hampered by the need to estimate realistic values for the many kinetic constants that determine the reaction rates. It is difficult to estimate these kinetic constants from available experimental data. To avoid this problem, modelers often resort to 'qualitative' modeling strategies, such as Boolean switching networks, but these models describe only the coarsest features of cell cycle regulation. In this paper we describe a hybrid approach that combines the best features of continuous differential equations and discrete Boolean networks. Cyclin abundances are tracked by piecewise linear differential equations for cyclin synthesis and degradation. Cyclin synthesis is regulated by transcription factors whose activities are represented by discrete variables (0 or 1) and likewise for the activities of the ubiquitin-ligating enzyme complexes that govern cyclin degradation. The discrete variables change according to a predetermined sequence, with the times between transitions determined in part by cyclin accumulation and degradation and as well by exponentially distributed random variables. The model is evaluated in terms of flow cytometry measurements of cyclin proteins in asynchronous populations of human cell lines. The few kinetic constants in the model are easily estimated from the experimental data. Using this hybrid approach, modelers can quickly create quantitatively accurate, computational models of protein regulatory networks in cells.
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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.