Network inference using steady-state data and Goldbeter-Koshland kinetics
By Chris J. Oates, Bryan T. J. Hennessy, Yiling Lu, Gordon B. Mills, Sach Mukherjee. 2012
19 citations recorded by the source corpus.
MOTIVATION 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. AVAILABILITY mukherjeelab.nki.nl/CODE/GK_Kinetics.zip CONTACT c.j.oates@warwick.ac.uk; s.mukherjee@nki.nl SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Subfields: Computational Theory and Mathematics, Molecular Biology
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Citations in the corpus
- Bayesian inference of chemical kinetic models from proposed reactions (2015, methodology): “A related sampling approach, reversible-jump MCMC (Green, 1995), has recently been used to infer kinetic models in systems biology (Oates et al., 2012).”