Parameter space exploration within dynamic simulations of signaling networks

Math Biosci Eng. 2013 Feb;10(1):103-20. doi: 10.3934/mbe.2013.10.103.

Abstract

We started offering an introduction to very basic aspects of molecular biology, for the reader coming from computer sciences, information technology, mathematics. Similarly we offered a minimum of information about pathways and networks in graph theory, for a reader coming from the bio-medical sector. At the crossover about the two different types of expertise, we offered some definition about Systems Biology. The core of the article deals with a Molecular Interaction Map (MIM), a network of biochemical interactions involved in a small signaling-network sub-region relevant in breast cancer. We explored robustness/sensitivity to random perturbations. It turns out that our MIM is a non-isomorphic directed graph. For non physiological directions of propagation of the signal the network is quite resistant to perturbations. The opposite happens for biologically significant directions of signal propagation. In these cases we can have no signal attenuation, and even signal amplification. Signal propagation along a given pathway is highly unidirectional, with the exception of signal-feedbacks, that again have a specific biological role and significance. In conclusion, even a relatively small network like our present MIM reveals the preponderance of specific biological functions over unspecific isomorphic behaviors. This is perhaps the consequence of hundreds of millions of years of biological evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Computer Simulation
  • ErbB Receptors / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • MAP Kinase Signaling System
  • Mathematics
  • Models, Biological
  • Nucleic Acids / metabolism
  • Proteins / physiology
  • Signal Transduction / physiology*
  • Software
  • Systems Biology / methods*
  • beta Catenin / metabolism

Substances

  • Nucleic Acids
  • Proteins
  • beta Catenin
  • ErbB Receptors
  • Extracellular Signal-Regulated MAP Kinases