title: Network inference using steady-state data and Goldbeter-Koshland kinetics. [corrected].
abstract: BACKGROUND
  Network inference approaches are widely used to shed light on regulatory interplay between molecular players such as genes and proteins. Biochemical processes underlying networks of interest (e.g. gene regulatory or protein signalling networks) are generally nonlinear. In many settings, knowledge is available concerning relevant chemical kinetics. However, existing network inference methods for continuous, steady-state data are typically rooted in statistical formulations, which do not exploit chemical kinetics to guide inference.
  
  
  RESULTS
  Herein, we present an approach to network inference for steady-state data that is rooted in non-linear descriptions of biochemical mechanism. We use equilibrium analysis of chemical kinetics to obtain functional forms that are in turn used to infer networks using steady-state data. The approach we propose is directly applicable to conventional steady-state gene expression or proteomic data and does not require knowledge of either network topology or any kinetic parameters. We illustrate the approach in the context of protein phosphorylation networks, using data simulated from a recent mechanistic model and proteomic data from cancer cell lines. In the former, the true network is known and used for assessment, whereas in the latter, results are compared against known biochemistry. We find that the proposed methodology is more effective at estimating network topology than methods based on linear models.
  
  
  BACKGROUND
  mukherjeelab.nki.nl/CODE/GK_Kinetics.zip
  
  
  BACKGROUND
  c.j.oates@warwick.ac.uk; s.mukherjee@nki.nl
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors: Centre for Complexity Science, University of Warwick, CV4 7AL, Coventry, UK. c.j.oates@warwick.ac.uk
authors: Chris J
authors: CJ
authors: Oates
authors: Bryan T
authors: BT
authors: Hennessy
authors: Yiling
authors: Y
authors: Lu
authors: Gordon B
authors: GB
authors: Mills
authors: Sach
authors: S
authors: Mukherjee
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology; D045744:Cell Line, Tumor; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D007700:Kinetics; D020935:MAP Kinase Signaling System; D008390:Markov Chains; D009010:Monte Carlo Method; D010766:Phosphorylation; D040901:Proteomics; D049490:Systems Biology / Q000379:methods*