cGMP signaling: probing antagonistic cyclic nucleotide platelet signals by modeling and experiment
Dandekar, T.; Friebe, A.; Feil, R.; Dittrich, M.; Breitenbach, T.; Englert, N.; Osmanoglu, O.; rukoyatkina, n.; Wangorsch, G.; Butt, E.; Gambaryan, S.
Show abstract
BackgroundThe cyclic nucleotides cAMP and cGMP inhibit platelet activation. ResultsWe extended an older model and systematically integrated drugs as external stimuli. Data driven modeling allowed us to design models that provide a quantitative output for quantitative input information. This relies on condensed information about involved regulation and modeling of pharmacological interventions by systematic optimization methods. By multi-experiment fitting, we validated our model optimizing the parameters of the model. In addition, we show how the output of the developed cGMP model can be used as input for a modular model of VASP phosphorylation and for the activity of cAMP and cGMP pathways in platelets. ConclusionsWe present a model for cGMP signaling and VASP phosphorylation, that allows to estimate drug action on any of the inhibitory cyclic nucleotide pathways (cGMP, cAMP) and has been validated by experimental data.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Unsupervised logic-based mechanism inference for network-driven biological processes 94%
- Buffering and total calcium levels determine the presence of oscillatory regimes in cardiac cells 93%
- Terminal heterocyst differentiation in the Anabaena patA mutant as a result of post-transcriptional modifications and molecular leakage 93%
Similar papers in this journal
- Discrete dynamic model of the mammalian sperm acrosome reaction: the influence of acrosomal pH and biochemical heterogeneity 95%
- Sensitivity and uncertainty analysis of two human atrial cardiac cell models using Gaussian process emulators 94%
- An organ-based multi-level model for glucose homeostasis: organ distributions, timing, and impact of blood flow 93%
Similar papers in this journal
- ELIMINATOR: Essentiality anaLysIs using MultIsystem Networks And inTeger prOgRamming 94%
- Exact calculation of stationary solution and parameter sensitivity analysis of stochastic continuous time Boolean models 94%
- Practical Identifiability in the Frame of Nonlinear Mixed Effects Models: the Example of the in vitro Erythropoiesis 94%
Similar papers in this journal
- Computational Evidence For Multi-Layer Crosstalk Between The Cadherin-11 And Pdgfr Pathways 96%
- Computational quantification of global effects induced by mutations and drugs in signaling networks of colorectal cancer cells. 96%
- Influence Of Energy Deficiency On The Molecular Processes Of Substantia Nigra Pars Compacta Cell For Understanding Parkinsonian Neurodegeneration: A Comprehensive Biophysical Computational Model 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.