Absolute units in Arabidopsis clock models up to U2020.3

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 parameters to match absolute RNA levels from the TiMet WP1a RNA dataset of Flis et al. 2015 in U2019.2 (first version was U2017.2), then reoptimises globally to match RNA timeseries, period and amplitude constraints to produce the U2019.3 model. [The first version U2017.3 also matched the protein levels that were independently predicted by a simple translation model, from those RNA levels].

This project then replaces regulation of the PRRs with repression by later-expressed genes (instead of activation by earlier ones, as in P2011/P2012/U2019) in the U2019.2 (first version U2017.2) model, to create the U2020.1 (first version U2018.1) model, then also rescales to match the protein levels that were independently predicted by a simple translation model from those RNA levels, in the U2020.2 (first U2018.2) model, and performs a global reoptimisation as above to form U2020.3 (U2018.3).

Early versions of these models with internal nomenclature remain private and are not included in the static Snapshot shared with the publication. The input data files, the computational environment for model development (a Docker image in the 'Reproducibility Toolset' assay) and the relevant model files are included here, as published in Urquiza and Millar, In Silico Plants, 2021. The biorXiv preprint version of the publication is linked here. The DOI for the publication was not yet available.

DOI: 10.5281/zenodo.5150794

Zenodo URL: https://zenodo.org/record/5150794

Created at: 31st Jul 2021 at 22:56

Contents

Rescaling the P2011 model to match RNA data

The P2011 model (linked in the Assay below) was rescaled to match TiMet RNA data in clock mutants from Flis et al. 2015, also linked here as separate mean and SD files. The raw TiMet data is available elsewhere on FAIRDOMHub.

TiMet RNA timeseries data and starting models

RNA timeseries data for Arabidopsis Col wild-type plants and clock mutants, as separate mean and SD files. The raw data is available on BioDare.ed.ac.uk, and is linked as 'Attribution' from elsewhere on FAIRDOMHub.

The starting models are included here in their original forms,
the P2011 model as an SBML L3V1 model file, and the KF2014 model of Fogelmark et al. shared as SBML; both prepared by Uriel Urquiza.

Processed TiMet WP1.1a RNA data, mean

Mean values of clock gene RNA data in absolute units of RNA copies per cell (calculated from copies per gFW, / 25 million cells/gFW) from TiMet WP1.1, RNA dataset ros (from rosettes). Note the Col data are from WP1.1, not substituted with Col from the LD12:12 of the WP1.2 photoperiod data set, as they were in Flis et al. 2015. Note also that cL_m in these data is taken from CCA1 only, not the average of CCA1 and LHY as in the data sets used for optimisation of P2011.2.1 in Flis et al. 2015.

The
...

  • TiMet_annaFlis_240714_mean.xls

Processed TiMet WP1.1a RNA data, SD

SD values of clock gene RNA data in absolute units of RNA copies per cell (calculated from copies per gFW, / 25 million cells/gFW) from TiMet WP1.1, RNA dataset ros (from rosettes). Note the Col data are from WP1.1, not substituted with Col from the LD12:12 of the WP1.2 photoperiod data set, as they were in Flis et al. 2015. Note also that cL_m in these data is taken from CCA1 only, not the average of CCA1 and LHY as in the data sets used for optimisation of P2011.2.1 in Flis et al. 2015.

The
...

  • TiMet_annaFlis_240714_sd.xls

Arabidopsis clock model P2011.1.2

This version is P2011.1.2, model ID PLM_71 version 1. Dynamics identical to P2011.1.1 of the Pokhilko et al. 2012 publication.

http://www.plasmo.ed.ac.uk/plasmo/models/download.shtml?accession=PLM_71&version=1

  • PLM_71.xml

P2011, U2019 and U2020 models and modelling resources

Collection of models used in the introduction of absolute units into A. thaliana circadian clock models, with software resources and documentation.
The models are inspired by P2011, published in Pokhilko et al 2012.
The study contains Assays that link to the P2011 starting model and the models U2019.1 - .3 and U2020.1 - .3. Each model is shared as a human-readable file in the Antimony language and the associated, machine-readable SBML file, which was automatically generated using the SBML export
...

P2011.1.2

P2011.1.2 written in Antimony and converted in SBML using python package Tellurium. Parameters values correspond to P2011.1.2

P2011.1.2 SBML

Model written in Antimony human-readable language and then translate into SBML using Tellurium

  • P2011.1.2.xml

P2011.1.2 Antimony

Model written in Antimony human-readable language, Model used in Pokhilko et al 2012

  • P2011.1.2.txt

Reproducibility tool set

This section contains the links to the tools used for reproducing the computational results presented in U2019. This is required because SloppyCell is under the risk of becoming rotting code. Using Docker we can assure some persistence for the computational environment that allows to run SloppyCell.

The associated git repository can be found in https://github.com/jurquiza/Urquiza2019a.git which can be cloned.

The docker image can either be pulled from the docker hub site

docker pull
...

Dockerfile

This file contains the dependencies required for running SloppyCell and Tellurium together using Jupyter notebooks. It can be used to create a Docker image by executing the command

docker build user/image:version .

The image used for the project can be pulled from Docker hub by typing

docker pull uurquiza/urquiza2019a_tellurium_sloppycell:latest

  • Dockerfile

U2019/U2020 models

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
...

U2019.1

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.

  • U2019.1.xml

U2019.2

Model derived from U2020.1 in which the transcription rates were rescaled to match the scale of TiMet data set. The gmX parameter in the model were fitted numerically. This has equivalent dynamics to P2011.1.2.

  • U2019.2.xml

U2019.3

U2020.2 derived model in which the was 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
...

  • U2019.3.xml

U2020.1

Model derived from U2020.1 for which the way the PRRs 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 pattern.
...

  • U2020.1.xml

U2020.2

Model derived from U2020.4 by fitting the scaling factors for matching TiMet data set and mutant networks.

  • U2020.2.xml

U2020.3

U2020.5 derived model in which the was 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
...

  • U2020.3.xml

U2019.1_ISSF

U2019.1 that simulates light condition with ISSF

  • U2019_1_ISSF.xml

U2019.2_ISSF

U2019.2 that simulates light condition with ISSF

  • U2019_2_ISSF.xml

U2019.3_ISSF

U2019.3 that simulates light condition with ISSF

  • U2019_3_ISSF.xml

U2020.1_ISSF

U2019.1 that simulates light condition with ISSF

  • U2020_1_ISSF.xml

U2020.2_ISSF

U2020.2 that simulates light condition with ISSF

  • U2020_2_ISSF.xml

U2020.3_ISSF

U2019.3 that simulates light condition with ISSF

  • U2020_3_ISSF.xml

U2019.1_ISSF_10xLD_LL

No description specified

  • U2019_1_ISSF_10LD_LL.xml

U2019.2_ISSF_10xLD_LL

No description specified

  • U2019_2_ISSF_10LD_LL.xml

U2019.3_ISSF_10xLD_LL

No description specified

  • U2019_3_ISSF_10LD_LL.xml

U2020.1_ISSF_10xLD_LL

No description specified

  • U2020_1_ISSF_10LD_LL.xml

U2020.2_ISSF_10xLD_LL

No description specified

  • U2020_2_ISSF_10LD_LL.xml

U2020.3_ISSF_10xLD_LL

No description specified

  • U2020_3_ISSF_10LD_LL.xml

U2019 equation listing

autogenerated equation listing from the SBML of U2019.3, as a .PDF file

  • U2019_3.pdf

U2020 equation listing

autogenerated equation listing from the SBML of U2020.3, as a .PDF file

  • U2020_3.pdf

Testing the inferred transcription rates of a dynamic, gene network model in absolute units

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,
...

Model evolution summary

Contains the summary of model evolution for the Arabidopsis clock in absolute units. In these process two alternative architectures were proposed and fitted to Flis A et al 2015 Open Biology.

  • Model_evolution_description

Parameter Values of U2019 and U2020 models

Listing of parameter values, identical to Supplementary Table 2 of the preprint and publication.

  • Supp_Table_2_params.xlsx
Fingerprints

These checksums allow you to check a Snapshot you have downloaded hasn't been modified. For details on how to use these please visit this guide

MD5: 59c8db685bee115dfbbfc73b8571c6f2

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Citation
Garcia, U. U., & Millar, A. J. (2021). Absolute units in Arabidopsis clock models up to U2020.3 [Data set]. Zenodo. https://doi.org/10.5281/ZENODO.5150794
Snapshots
Snapshot 3 (4th Aug 2021) DOI
Snapshot 2 (31st Aug 2021) DOI
Snapshot 1 (31st Jul 2021) DOI Exported to Zenodo
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Created: 31st Jul 2021 at 22:56

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