The circadian clock coordinates plant physiology and development. Mathematical clock models have provided a rigorous framework to understand how the observed rhythms emerge from disparate, molecular processes. However, models of the plant clock have largely been built and tested against RNA timeseries data in arbitrary, relative units. This limits model transferability, refinement from biochemical data and applications in synthetic biology. Here, we incorporate absolute mass units into a detailed, gene circuit model of the clock in Arabidopsis thaliana. We reinterpret the established P2011 model, highlighting a transcriptional activator that overlaps the function of REVEILLE 8/LHYCCA1LIKE 5, and refactor dynamic equations for the Evening Complex. The U2020 model incorporates the repressive regulation of PRR genes, a key feature of the most detailed clock model F2014, without greatly increasing model complexity. We tested the experimental error distributions of qRTPCR data calibrated for units of RNA transcripts/cell and of circadian period estimates, in order to link the models to data more appropriately. U2019 and U2020 models were constrained using these data types, recreating previouslydescribed circadian behaviours with RNA metabolic processes in absolute units. To test their inferred rates, we estimated a distribution of observed, transcriptomewide transcription rates (Plant Empirical Transcription Rates, PETR) in units of transcripts/cell/hour. The PETR distribution and the equivalent degradation rates indicated that the models’ predicted rates are biologically plausible, with individual exceptions. In addition to updated, explanatory models of the plant clock, this validation process represents an advance in biochemical realism for models of plant gene regulation.
SEEK ID: https://fairdomhub.org/publications/599
DOI: 10.1101/2021.03.18.436071
Projects: Millar group
Publication type: Tech report
Citation: biorxiv;2021.03.18.436071v1,[Preprint]
Date Published: 20th Mar 2021
Registered Mode: by DOI
Authors: Uriel UrquizaGarcia, Andrew J Millar
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Created: 21st Mar 2021 at 23:04
Last updated: 21st Mar 2021 at 23:08
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Projects: Millar group, TiMet, PHYTOCAL: Phytochrome Control of Resource Allocation and Growth in Arabidopsis and in Brassicaceae crops, POP  the Parameter Optimisation Problem, Regulation of flowering time in natural conditions, PlaSMo model repository
Institutions: University of Edinburgh
https://orcid.org/0000000317563654Roles: Project Coordinator, Vice Coordinator
Expertise: circadian rhythms, arabidopsis thaliana, Mathematical modelling, Data Management, Molecular Biology, Genetics, Deterministic modelling of gene regulation networks, Systems Biology
Tools: Transcriptomics, Proteomics, Deterministic models, Stochastic models, SBML
Projects: Millar group, PlaSMo model repository, PHYTOCAL: Phytochrome Control of Resource Allocation and Growth in Arabidopsis and in Brassicaceae crops, Light and plant development, Light control of leaf development, Toggle switch, Reduce Complexity (RCO) reconstruction, Model Driven Prime Editing, PULSE 2.0, Plant optogenetics
Institutions: University of Edinburgh, Heinrich Heine University of Düsseldorf
https://orcid.org/0000000279755013Roles: Postdoc
Expertise: circadian rhythms, Systems Biology, arabidopsis thaliana, Synthetic Biology, Time Series Analysis, photobiology, NanoLUC, LUC, Automation
SynthSys is the University of Edinburgh's research organisation in interdisciplinary, Synthetic and Systems Biology, founded in 2012 as the successor to the Centre for Systems Biology at Edinburgh (CSBE).
Projects: Millar group, PHYTOCAL: Phytochrome Control of Resource Allocation and Growth in Arabidopsis and in Brassicaceae crops, TiMet, POP  the Parameter Optimisation Problem, Regulation of flowering time in natural conditions, PlaSMo model repository
Web page: http://www.synthsys.ed.ac.uk
Andrew Millar's research group, University of Edinburgh
Programme: SynthSys
Public web page: http://www.amillar.org
Organisms: Escherichia coli, Arabidopsis thaliana, Ostreococcus tauri
The dataset presents mathematical models of the gene regulatory network of the circadian clock, in the plant Arabidopsis thaliana. The work is published in UrquizaGarcia and Millar, Testing the inferred transcription rates of a dynamic, gene network model in absolute units, In Silico Plants, 2021.
Starting from the P2011 model, this project corrects theoretical issues (EC steady state binding assumption) to form an intermediate model (first version U2017.1; published as U2019.1) model, rescales ...
Submitter: Andrew Millar
Studies: P2011, U2019 and U2020 models and modelling resources, Rescaling the P2011 model to match RNA data
Assays: P2011.1.2, Reproducibility tool set, TiMet RNA timeseries data and starting models, U2019/U2020 models
Snapshots: Snapshot 1, Snapshot 2, Snapshot 3
Collection of clock models that rescale transcript variables to account for absolute units. The relationship between models is summarised in the attached 'model evolution' document and in more detail in the linked publications (preprint version linked in the Snapshot; publication Urquiza and Millar, In Silico Plants 2021 did not have a DOI when Snapshot was created).
Each model is presented three times,

 without a light:dark cycle,

 with an ISSF (Adams et al. JBR 2012) that is set up for ...
Submitter: Uriel Urquiza Garcia
Biological problem addressed: Gene Regulatory Network
Investigation: Absolute units in Arabidopsis clock models up t...
Organisms: Arabidopsis thaliana : Col0 wild type (wildtype / wildtype)
Models: U2019 equation listing, U2019.1, U2019.1_ISSF, U2019.1_ISSF_10xLD_LL, U2019.2, U2019.2_ISSF, U2019.2_ISSF_10xLD_LL, U2019.3, U2019.3_ISSF, U2019.3_ISSF_10xLD_LL, U2020 equation listing, U2020.1, U2020.1_ISSF, U2020.1_ISSF_10xLD_LL, U2020.2, U2020.2_ISSF, U2020.2_ISSF_10xLD_LL, U2020.3, U2020.3_ISSF, U2020.3_ISSF_10xLD_LL
SOPs: No SOPs
Data files: No Data files
Snapshots: No snapshots
Model derived from U2019.2, fitted to TiMet data mutants data set. Fixed parameters are scaling factors, COP1 and cP parameters. The rest of the parameters were left optimisable. The networks used in the fitting include WT, lhycca1, prr79, toc1, gi and ztl. The ztl network was only used for fixing the period in this mutant. Then final parameter values for transcription rated were obtained by taking the product of scaling factor and either transcription or translation, the latter required for ...
Creators: Andrew Millar, Uriel Urquiza Garcia
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Not specified
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
Model derived from U2019.1 in which the transcription rates were rescaled to match the scale of TiMet data set for absolute units of RNA concentration. The gmX scaling parameters in the model were fitted numerically. This model has equivalent dynamics to P2011.1.2.
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
Model derived from U2020.2, fitted to the TiMet RNA data for wildtype and clock mutants. Fixed parameters are scaling factors, COP1 and cP parameters. The rest of the parameters were left optimisable. The networks used in the fitting include WT, lhycca1, prr79, toc1, gi and ztl. The ztl network was only used for fixing the period in this mutant. Then final parameter values for transcription rates were obtained by taking the product of scaling factor and either transcription or translation, the ...
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
Model derived from U2020.1 by fitting the scaling factors for matching TiMet data set for wildtype and clock mutants, in absolute units.
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
Model derived from U2019.1, in which the way the PRR genes are regulated is modified. Repression mechanism introduced Instead of activation between the PRRs for producing the wave of expression. This is inspired in the result of three models P2012, F2014 and F2016. P2012 introduced TOC1 repression in earlier genes relative to its expression. F2014 introduced also the backward repression of PRR9  PRR7  PRR5, TOC1. However little attention was given to why there is a sharper expression ...
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
autogenerated equation listing from the SBML of U2020.3, as a .PDF file
Creators: Andrew Millar, Uriel Urquiza Garcia
Submitter: Andrew Millar
Model type: Ordinary differential equations (ODE)
Model format: PDF (Model description)
Environment: Not specified
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
autogenerated equation listing from the SBML of U2019.3, as a .PDF file
Creators: Andrew Millar, Uriel Urquiza Garcia
Submitter: Andrew Millar
Model type: Ordinary differential equations (ODE)
Model format: PDF (Model description)
Environment: Not specified
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Not specified
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
U2019.3 that simulates light condition with ISSF
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
U2020.2 that simulates light condition with ISSF
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
U2019.1 that simulates light condition with ISSF
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
U2019.3 that simulates light condition with ISSF
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
U2019.2 that simulates light condition with ISSF
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
U2019.1 that simulates light condition with ISSF
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models
Model derived from P2011.1.2 in which the steady state assumptions for the Evening complex in P2011 were eliminated. After eliminating these assumptions the model was fitted to the original dynamics of P2011.1.2 for the networks WT, lhycca1, prr79, toc1, gi, ztl. In particular for the lhycca1 double mutant only the repressive "arms" (edges) for cL were set to zero. The parameter values or cP and for COP1 variables were fixed as these have been fitted before in Pokhilko et al 2012 Mol Sys Bio.
Creators: Uriel Urquiza Garcia, Andrew Millar
Submitter: Uriel Urquiza Garcia
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t...
Studies: P2011, U2019 and U2020 models and modelling res...
Assays: U2019/U2020 models