Nov 9, 2018

Metastable regimes and tipping points of biochemical networks with potential applications in precision medicine

BioRxiv : the Preprint Server for Biology
Satya Swarup SamalOvidiu Radulescu

Abstract

The concept of attractor of dynamic biochemical networks has been used to explain cell types and cell alterations in health and disease. We have recently proposed an extension of the notion of attractor to take into account metastable regimes, defined as long lived dynamical states of the network. These regimes correspond to slow dynamics on low dimensional invariant manifolds of the biochemical networks. Methods based on tropical geometry allow to compute the metastable regimes and represent them as polyhedra in the space of logarithms of the species concentrations. We are looking for sensitive parameters and tipping points of the networks by analyzing how these polyhedra depend on the model parameters. Using the coupled MAPK and PI3K/Akt signaling networks as an example, we test the idea that large changes of the metastable states can be associated to cancer disease specific alterations of the network. In particular, we show that for model parameters representing protein concentrations, the protein differential level between tumors of different types is reasonably reflected in the sensitivity scores, with sensitive parameters corresponding to differential proteins.

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

AKT1
2-Dimensional
Mitogen-Activated Protein Kinases
Neoplasms
Anatomical Space Structure
PIK3CG wt Allele
Pharmaceutical Preparations
Protein Serine/Threonine Kinase Activity
MAP Kinase Gene
Cell Type

About this Paper

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.