Agent-based re-engineering of ErbB signaling: a modeling pipeline for integrative systems biology

Das, Arya A.; Darsana, T Ajayakumar; Jacob, Elizabeth

doi:10.1093/bioinformatics/btw709

Cited by 6 publications

(2 citation statements)

References 26 publications

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“…Pogson et al also explored the NF‐κB signaling pathway via ABM and showed that they could capture the dynamics observed by real‐time single cell analysis . More recently, Das et al studied the ErbB signaling pathway . ErbB receptors are responsible for propagation of signals throughout the cell to regulate cell proliferation, differentiation, migration, adhesion, apoptosis, and embryogenesis.…”

Section: Examples Of Molecular Agent‐based Modelingmentioning

confidence: 99%

Agent‐Based Modeling in Molecular Systems Biology

Soheilypour

Mofrad

2018

BioEssays

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Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease.

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Section: Examples Of Molecular Agent‐based Modelingmentioning

confidence: 99%

Agent‐Based Modeling in Molecular Systems Biology

Soheilypour

Mofrad

2018

BioEssays

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“…ABM also has the advantage that it enables spatial relationships to be considered, whereas this is not easily done for equation-based methods. ABM has been used in many areas, including in sociology, town-planning and economics, but has only been applied to the study of receptors in a few instances, with a primary focus on the modelling of complex intracellular signalling pathways [ 15 , 16 ]. In ABM, it is relatively easy to incorporate rules that govern the clustering of receptors such as ligand binding, location, phosphorylation and interactions with other receptors and signalling molecules, and thereby study their interactions.…”

Section: Introductionmentioning

confidence: 99%

Experimental validation of computerised models of clustering of platelet glycoprotein receptors that signal via tandem SH2 domain proteins

et al. 2022

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The clustering of platelet glycoprotein receptors with cytosolic YxxL and YxxM motifs, including GPVI, CLEC-2 and PEAR1, triggers activation via phosphorylation of the conserved tyrosine residues and recruitment of the tandem SH2 (Src homology 2) domain effector proteins, Syk and PI 3-kinase. We have modelled the clustering of these receptors with monovalent, divalent and tetravalent soluble ligands and with transmembrane ligands based on the law of mass action using ordinary differential equations and agent-based modelling. The models were experimentally evaluated in platelets and transfected cell lines using monovalent and multivalent ligands, including novel nanobody-based divalent and tetravalent ligands, by fluorescence correlation spectroscopy. Ligand valency, receptor number, receptor dimerisation, receptor phosphorylation and a cytosolic tandem SH2 domain protein act in synergy to drive receptor clustering. Threshold concentrations of a CLEC-2-blocking antibody and Syk inhibitor act in synergy to block platelet aggregation. This offers a strategy for countering the effect of avidity of multivalent ligands and in limiting off-target effects.

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