Understanding hormonal crosstalk in Arabidopsis root development via emulation and history matching

Abstract A major challenge in plant developmental biology is to understand how plant growth is coordinated by interacting hormones and genes. To meet this challenge, it is important to not only use experimental data, but also formulate a mathematical model. For the mathematical model to best describe the true biological system, it is necessary to understand the parameter space of the model, along with the links between the model, the parameter space and experimental observations. We develop sequential history matching methodology, using Bayesian emulation, to gain substantial insight into biological model parameter spaces. This is achieved by finding sets of acceptable parameters in accordance with successive sets of physical observations. These methods are then applied to a complex hormonal crosstalk model for Arabidopsis root growth. In this application, we demonstrate how an initial set of 22 observed trends reduce the volume of the set of acceptable inputs to a proportion of 6.1 × 10−7 of the original space. Additional sets of biologically relevant experimental data, each of size 5, reduce the size of this space by a further three and two orders of magnitude respectively. Hence, we provide insight into the constraints placed upon the model structure by, and the biological consequences of, measuring subsets of observations.

[1]  M. Kennedy,et al.  Gaussian process emulation for second-order Monte Carlo simulations , 2011 .

[2]  Jenný Brynjarsdóttir,et al.  Learning about physical parameters: the importance of model discrepancy , 2014 .

[3]  Christopher C. Drovandi,et al.  Using History Matching for Prior Choice , 2016, Technometrics.

[4]  C. Holmes,et al.  Approximate Models and Robust Decisions , 2014, 1402.6118.

[5]  James O. Berger,et al.  An overview of robust Bayesian analysis , 1994 .

[6]  Anthony O'Hagan,et al.  Bayes Linear Estimators for Randomized Response Models , 1987 .

[7]  Jeremy E. Oakley,et al.  Efficient History Matching of a High Dimensional Individual-Based HIV Transmission Model , 2017, SIAM/ASA J. Uncertain. Quantification.

[8]  Michael Goldstein,et al.  Reified Bayesian modelling and inference for physical systems , 2009 .

[9]  Charles J. Geyer,et al.  Introduction to Markov Chain Monte Carlo , 2011 .

[10]  Keith Lindsey,et al.  Interaction of PLS and PIN and hormonal crosstalk in Arabidopsis root development , 2013, Front. Plant Sci..

[11]  Jeremy E. Oakley,et al.  Universal test, treat, and keep: improving ART retention is key in cost-effective HIV control in Uganda , 2017, BMC Infectious Diseases.

[12]  R. A. Fisher,et al.  Design of Experiments , 1936 .

[13]  David Higdon,et al.  THE COYOTE UNIVERSE. II. COSMOLOGICAL MODELS AND PRECISION EMULATION OF THE NONLINEAR MATTER POWER SPECTRUM , 2009, 0902.0429.

[14]  D. Oliver,et al.  Recent progress on reservoir history matching: a review , 2011 .

[15]  Robin K. S. Hankin,et al.  Introducing BACCO, an R Bundle for Bayesian Analysis of Computer Code Output , 2005 .

[16]  Keith Lindsey,et al.  Crosstalk Complexities between Auxin, Cytokinin, and Ethylene in Arabidopsis Root Development: From Experiments to Systems Modeling, and Back Again. , 2017, Molecular plant.

[17]  Thomas J. Santner,et al.  Design and analysis of computer experiments , 1998 .

[18]  Keith Lindsey,et al.  A recovery principle provides insight into auxin pattern control in the Arabidopsis root , 2017, Scientific Reports.

[19]  Keith Lindsey,et al.  Some fundamental aspects of modeling auxin patterning in the context of auxin-ethylene-cytokinin crosstalk , 2015, Plant signaling & behavior.

[20]  Antony M. Overstall,et al.  Multivariate emulation of computer simulators: model selection and diagnostics with application to a humanitarian relief model , 2015, Journal of the Royal Statistical Society. Series C, Applied statistics.

[21]  Michael P H Stumpf,et al.  How to deal with parameters for whole-cell modelling , 2017, Journal of The Royal Society Interface.

[22]  Paul D. Arendt,et al.  Quantification of model uncertainty: Calibration, model discrepancy, and identifiability , 2012 .

[23]  A. Forrester Black-box calibration for complex-system simulation , 2010, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[24]  Michael Goldstein,et al.  Bayes linear uncertainty analysis for oil reservoirs based on multiscale computer experiments. , 2010 .

[25]  Michael Goldstein,et al.  Rejoinder - Galaxy Formation : a Bayesian uncertainty analysis. , 2010 .

[26]  B. Palsson,et al.  Formulating genome-scale kinetic models in the post-genome era , 2008, Molecular systems biology.

[27]  Andrea Castelletti,et al.  A general framework for Dynamic Emulation Modelling in environmental problems , 2012, Environ. Model. Softw..

[28]  Richard Wilkinson,et al.  Accelerating ABC methods using Gaussian processes , 2014, AISTATS.

[29]  Ian Vernon,et al.  Efficient uniform designs for multi-wave computer experiments , 2013, 1309.3520.

[30]  A. O'Hagan,et al.  Bayesian calibration of computer models , 2001 .

[31]  Olivier Roustant,et al.  Cross-Validation Estimations of Hyper-Parameters of Gaussian Processes with Inequality Constraints☆ , 2015 .

[32]  P. Whittle On the Smoothing of Probability Density Functions , 1958 .

[33]  Hugh A. Chipman,et al.  GPfit: An R Package for Fitting a Gaussian Process Model to Deterministic Simulator Outputs , 2013, 1305.0759.

[34]  Jian Hou,et al.  An Automatic History Matching Method of Reservoir Numerical Simulation Based on Improved Genetic Algorithm , 2012 .

[35]  Andy Hart,et al.  A Bayes Linear Approach to Weight-of-Evidence Risk Assessment for Skin Allergy , 2013 .

[36]  Neil Swainston,et al.  Towards a genome-scale kinetic model of cellular metabolism , 2010, BMC Systems Biology.

[37]  Keith Lindsey,et al.  Modelling and experimental analysis of hormonal crosstalk in Arabidopsis , 2010, Molecular systems biology.

[38]  T. J. Mitchell,et al.  Bayesian Prediction of Deterministic Functions, with Applications to the Design and Analysis of Computer Experiments , 1991 .

[39]  M. D. McKay,et al.  A comparison of three methods for selecting values of input variables in the analysis of output from a computer code , 2000 .

[40]  Jakub Szymanik,et al.  Methods Results & Discussion , 2007 .

[41]  Anthony O'Hagan,et al.  Diagnostics for Gaussian Process Emulators , 2009, Technometrics.

[42]  A. O'Hagan,et al.  Gaussian process emulation of dynamic computer codes , 2009 .

[43]  Sean May,et al.  Cytokinin Regulation of Auxin Synthesis in Arabidopsis Involves a Homeostatic Feedback Loop Regulated via Auxin and Cytokinin Signal Transduction[W][OA] , 2010, Plant Cell.

[44]  Radford M. Neal Monte Carlo Implementation of Gaussian Process Models for Bayesian Regression and Classification , 1997, physics/9701026.

[45]  Junli Liu,et al.  Bayesian uncertainty analysis for complex systems biology models: emulation, global parameter searches and evaluation of gene functions , 2016, BMC Systems Biology.

[46]  I. Couckuyt,et al.  Gaussian Processes for history-matching: application to an unconventional gas reservoir , 2017, Computational Geosciences.

[47]  Guido Santos,et al.  The (Mathematical) Modeling Process in Biosciences , 2015, Front. Genet..

[48]  Carl E. Rasmussen,et al.  In Advances in Neural Information Processing Systems , 2011 .

[49]  Rui Alves,et al.  Tools for kinetic modeling of biochemical networks , 2006, Nature Biotechnology.

[50]  Keith Lindsey,et al.  Spatiotemporal modelling of hormonal crosstalk explains the level and patterning of hormones and gene expression in Arabidopsis thaliana wild-type and mutant roots , 2015, The New phytologist.

[51]  Michael Goldstein,et al.  Galaxy Formation: Bayesian History Matching for the Observable Universe , 2014, 1405.4976.

[52]  Ian Vernon,et al.  Galaxy formation : a Bayesian uncertainty analysis. , 2010 .

[53]  David Welch,et al.  Approximate Bayesian computation scheme for parameter inference and model selection in dynamical systems , 2009, Journal of The Royal Society Interface.

[54]  Jeremy E. Oakley,et al.  Approximate Bayesian Computation and simulation based inference for complex stochastic epidemic models , 2018 .

[55]  Keith Lindsey,et al.  Modelling Plant Hormone Gradients , 2015 .

[56]  Carl E. Rasmussen,et al.  Gaussian processes for machine learning , 2005, Adaptive computation and machine learning.

[57]  Michael Andrew Christie,et al.  Population MCMC methods for history matching and uncertainty quantification , 2010, Computational Geosciences.

[58]  Michael Goldstein,et al.  History matching for exploring and reducing climate model parameter space using observations and a large perturbed physics ensemble , 2013, Climate Dynamics.

[59]  Richard G. Everitt,et al.  A rare event approach to high-dimensional approximate Bayesian computation , 2016, Statistics and Computing.

[60]  Michael Goldstein,et al.  Small Sample Bayesian Designs for Complex High-Dimensional Models Based on Information Gained Using Fast Approximations , 2009, Technometrics.

[61]  Michael Goldstein,et al.  Bayes linear analysis of imprecision in computer models, with application to understanding galaxy formation. , 2009 .

[62]  I. Andrianakis,et al.  History matching of a complex epidemiological model of human immunodeficiency virus transmission by using variance emulation , 2016, Journal of the Royal Statistical Society. Series C, Applied statistics.

[63]  Robert Jacob,et al.  Statistical emulation of climate model projections based on precomputed GCM runs , 2013 .

[64]  Andrew Gelman,et al.  Handbook of Markov Chain Monte Carlo , 2011 .

[65]  Michael Goldstein,et al.  Bayesian Forecasting for Complex Systems Using Computer Simulators , 2001 .

[66]  Michael Goldstein,et al.  Assessing Model Adequacy , 2013 .

[67]  Michael Beer,et al.  SAMPLING SCHEMES FOR HISTORY MATCHING USING SUBSET SIMULATION , 2017 .

[68]  D. J. Nott,et al.  Approximate Bayesian Computation and Bayes’ Linear Analysis: Toward High-Dimensional ABC , 2011, 1112.4755.

[69]  W. B. Whalley,et al.  The use of fractals and pseudofractals in the analysis of two-dimensional outlines: Review and further exploration , 1989 .

[70]  Kristin A. Moore,et al.  Parent Marital Quality and the Parent–Adolescent Relationship: Effects on Sexual Activity among Adolescents and Youth , 2009 .

[71]  Jeremy E. Oakley,et al.  Bayesian History Matching of Complex Infectious Disease Models Using Emulation: A Tutorial and a Case Study on HIV in Uganda , 2015, PLoS Comput. Biol..

[72]  J. Rougier,et al.  Bayes Linear Calibrated Prediction for Complex Systems , 2006 .

[73]  F. Pukelsheim The Three Sigma Rule , 1994 .

[74]  R. Wilkinson Approximate Bayesian computation (ABC) gives exact results under the assumption of model error , 2008, Statistical applications in genetics and molecular biology.

[75]  W. Möbius,et al.  Physical and Mathematical Modeling in Experimental Papers , 2015, Cell.