Vester's Sensitivity Model for Genetic Networks with Time-Discrete Dynamics


Moreno L. A. , DEFTERLİ Ö., Fuegenschuh A., Weber G.

1st International Conference on Algorithms for Computational Biology (AlCoB), Tarragona, Spain, 1 - 03 July 2014, vol.8542, pp.35-46 identifier

  • Publication Type: Conference Paper / Full Text
  • Volume: 8542
  • City: Tarragona
  • Country: Spain
  • Page Numbers: pp.35-46
  • Keywords: Linear Programming, Parameter Estimation, Discrete Dynamical System, Sensitivity Analysis, Genetic Networks, Operational Research, Systems Biology, OPTIMIZATION, SIMULATION

Abstract

We propose a new method to explore the characteristics of genetic networks whose dynamics are described by a linear discrete dynamical model x(t+1) = Ax(t). The gene expression data x(t) is given for various time points and the matrix A of interactions among the genes is unknown. First we formulate and solve a parameter estimation problem by linear programming in order to obtain the entries of the matrix A. We then use ideas from Vester's Sensitivity Model, more precisely, the Impact Matrix, and the determination of the Systemic Roles, to understand the interactions among the genes and their role in the system. The method identifies prominent outliers, that is, the most active, reactive, buffering and critical genes in the network. Numerical examples for different datasets containing mRNA transcript levels during the cell cycle of budding yeast are presented.