Parametric and non-parametric gradient matching for network inference: a comparison.

Leander Dony, Fei He, Michael P H Stumpf
Author Information
  1. Leander Dony: Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
  2. Fei He: Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
  3. Michael P H Stumpf: Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK. mstumpf@unimelb.edu.au. ORCID

Abstract

BACKGROUND: Reverse engineering of gene regulatory networks from time series gene-expression data is a challenging problem, not only because of the vast sets of candidate interactions but also due to the stochastic nature of gene expression. We limit our analysis to nonlinear differential equation based inference methods. In order to avoid the computational cost of large-scale simulations, a two-step Gaussian process interpolation based gradient matching approach has been proposed to solve differential equations approximately.
RESULTS: We apply a gradient matching inference approach to a large number of candidate models, including parametric differential equations or their corresponding non-parametric representations, we evaluate the network inference performance under various settings for different inference objectives. We use model averaging, based on the Bayesian Information Criterion (BIC), to combine the different inferences. The performance of different inference approaches is evaluated using area under the precision-recall curves.
CONCLUSIONS: We found that parametric methods can provide comparable, and often improved inference compared to non-parametric methods; the latter, however, require no kinetic information and are computationally more efficient.

Keywords

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Grants

  1. BB/N003608/1/Biotechnology and Biological Sciences Research Council

MeSH Term

Algorithms
Gene Regulatory Networks
Normal Distribution

Word Cloud

Created with Highcharts 10.0.0inferencematchingdifferentialbasedmethodsgradientnon-parametricdifferentgenecandidateapproachequationsparametricnetworkperformanceBACKGROUND:Reverseengineeringregulatorynetworkstimeseriesgene-expressiondatachallengingproblemvastsetsinteractionsalsoduestochasticnatureexpressionlimitanalysisnonlinearequationorderavoidcomputationalcostlarge-scalesimulationstwo-stepGaussianprocessinterpolationproposedsolveapproximatelyRESULTS:applylargenumbermodelsincludingcorrespondingrepresentationsevaluatevarioussettingsobjectivesusemodelaveragingBayesianInformationCriterionBICcombineinferencesapproachesevaluatedusingareaprecision-recallcurvesCONCLUSIONS:foundcanprovidecomparableoftenimprovedcomparedlatterhoweverrequirekineticinformationcomputationallyefficientParametricinference:comparisonGeneregulationGradientNetworkSystemsbiology

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