ArticleJournal of the Royal Society, Interface2016
Linear models of activation cascades: analytical solutions and coarse-graining of delayed signal transduction.
Article in Journal of the Royal Society, Interface, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
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- The ups and downs of biological oscillators: a comparison of time-delayed negative feedback mechanisms.Journal of the Royal Society, Interface · 2023Article
- Systematic inference identifies a major source of heterogeneity in cell signaling dynamics: The rate-limiting step number.Science advances · 2022Article
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- Memorizing environmental signals through feedback and feedforward loops.Current opinion in cell biology · 2021Review
- Molecular switch architecture determines response properties of signaling pathways.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Exact solutions and equi-dosing regimen regions for multi-dose pharmacokinetics models with transit compartments.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- It's about time: Analysing simplifying assumptions for modelling multi-step pathways in systems biology.PLoS computational biology · 2020Article
- A network-based analysis for mining the risk pathways in glioblastoma.Oncology letters · 2019Article
- Tensor clustering with algebraic constraints gives interpretable groups of crosstalk mechanisms in breast cancer.Journal of the Royal Society, Interface · 2019Article
- Spatial modeling of the membrane-cytosolic interface in protein kinase signal transduction.PLoS computational biology · 2018Article
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- Compound stress response in stomatal closure: a mathematical model of ABA and ethylene interaction in guard cells.BMC systems biology · 2012Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cellular signal transduction usually involves activation cascades, the sequential activation of a series of proteins following the reception of an input signal. Here, we study the classic model of weakly activated cascades and obtain analytical solutions for a variety of inputs. We show that in the special but important case of optimal gain cascades (i.e. when the deactivation rates are identical) the downstream output of the cascade can be represented exactly as a lumped nonlinear module containing an incomplete gamma function with real parameters that depend on the rates and length of the cascade, as well as parameters of the input signal. The expressions obtained can be applied to the non-identical case when the deactivation rates are random to capture the variability in the cascade outputs. We also show that cascades can be rearranged so that blocks with similar rates can be lumped and represented through our nonlinear modules. Our results can be used both to represent cascades in computational models of differential equations and to fit data efficiently, by reducing the number of equations and parameters involved. In particular, the length of the cascade appears as a real-valued parameter and can thus be fitted in the same manner as Hill coefficients. Finally, we show how the obtained nonlinear modules can be used instead of delay differential equations to model delays in signal transduction.
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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.