A coherent framework for multiresolution analysis of biological networks with "memory": Ras pathway, cell cycle, and immune system

Proc Natl Acad Sci U S A. 2005 May 3;102(18):6245-50. doi: 10.1073/pnas.0500554102. Epub 2005 Apr 20.

Abstract

Various biological processes exhibit characteristics that vary dramatically in response to different input conditions or changes in the history of the process itself. One of the examples studied here, the Ras-PKC-mitogen-activated protein kinase (MAPK) bistable pathway, follows two distinct dynamics (modes) depending on duration and strength of EGF stimulus. Similar examples are found in the behavior of the cell cycle and the immune system. A classification methodology, based on time-frequency analysis, was developed and tested on these systems to understand global behavior of biological processes. Contrary to most traditionally used statistical and spectral methods, our approach captures complex functional relations between parts of the systems in a simple way. The resulting algorithms are capable of analyzing and classifying sets of time-series data obtained from in vivo or in vitro experiments, or in silico simulation of biological processes. The method was found to be considerably stable under stochastic noise perturbation and, therefore, suitable for the analysis of real experimental data.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms*
  • Cell Cycle / physiology*
  • Immunity / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Theoretical*
  • Protein Kinase C / metabolism
  • Signal Transduction / physiology*
  • Systems Biology*
  • Time Factors
  • ras Proteins / metabolism

Substances

  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • ras Proteins