Prediction and analysis of phenotypes in the Arabidopsis clock mutant <i>prr7 prr9</i> using the Framework Model v2 (FMv2)

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).

Andrew Millar's research group, University of Edinburgh

EU FP7 collaborative project TiMet, award number 245143. Funded 2010-2015. "TiMet assembles world leaders in experimental and theoretical plant systems biology to advance understanding of the regulatory interactions between the circadian clock and plant metabolism, and their emergent effects on whole-plant growth and productivity."

Modelling and experiments for FMv2 components.

Simulations, parameter sensitivity analysis etc. for FMv2

Modelling and experiments for FMv2 as a whole; Testing Framework Model version 2 (FMv2)

Modelling and experiments for FMv2 as a whole; Testing Framework Model version 2 (FMv2)

Modelling and experiments for FMv2 as a whole; Testing Framework Model version 2 (FMv2)

Model simulations compared to experimental data from the literature (publications from Mizuno lab are linked), testing the FMv2.

Modelling and experiments for FMv2 as a whole; Testing Framework Model version 2 (FMv2)

Follow-up to the validation experiments on FMv2, testing candidate mechanisms for high malate and fumarate accumulation in the Arabidopsis double mutant prr7prr9 and its parent accession Col. New collaborations with the groups of Teresa Fitzpatrick and TiMet partner Samuel Zeeman.

Assorted files prepared during the publication process of the FMv2, its validation and testing, mostly focussed on the Arabidopsis double mutant prr7prr9 and its parent accession Col. Data from other studies that are described separately, and linked by Atribution to the File records under this Study.

Metabolite analysis in clock mutants: Col-0 parent and mutants gi-201, toc1-101 and prr7prr9; WS parent and lhy/cca1 double mutant. Plants grown in Golm and harvested at End of Day and End of Night, , assays 22 major metabolites. More detail on TiMet wiki if required. Heteroscedastic t-tests to highlight most significant changes, without multiple-testing correction.

Leaf number at flowering data from literature for prr7 prr9 and Col wild-type plants under long photoperiods and short photoperiods

Seedling hypocotyl data from literature for prr7 prr9 and Col wild-type plants under various photoperiods

RNA timeseries data from TiMet for clock genes in prr7 prr9 and Col wild-type plants under 12L:12D cycle and LL

effects of 1% increase in each parameter, more detailed analysis of water content

correlations of starch mobilisation and fresh weight under single parameter changes

Combination of multiple sub-models to form Framework Model version 2

Comparison of simulated wild-type and prr7prr9 double mutant under 12L:12D cycles. Simulation with CVODE simulator via SBSI v1.5 framework.

Biomass, leaf number and metabolites in Col0 (WT), prr7, prr7prr9, and lsf1. Metabolite data from plants after 28 days of growth were analysed most (27 days 'end of night', 28 days 'end of day' and 'end of night'). The data file also includes data from 21 days of growth ('end of day' and 'end of night'), which is useful for comparison to early-flowering plants not tested here, such as the lhycca1 double mutant, that flower before 28 days, altering their physiology.

Biomass (fresh mass, dry mass), leaf numbers, leaf area, gas exchange and 12 metabolites in Col0 (WT), prr7prr9, and lsf1 (presented in the preprint/paper) and pgm (not analysed further).

Biomass (fresh mass, dry mass), leaf numbers, leaf area, gas exchange and 12 metabolites in Col0 (WT), prr7prr9, and pgm at days 29 and 35, presented in the preprint/publication, with most data also for Col and lhycca1 at days 21/22/23, not analysed further.

We suggest that the lower carbon assimilation rate measured in lhycca1 (see gas exchange data) might allow a calibirated simulation in the FMv2 model in future to incorporate the indirect effects of nightly carbon starvation in this genotype ...

Simulation data from FMv2 calibrated for experiment L&H2, an experiment run at 18.5C instead of the 20.5C of the replicate and related studies. The Excel file includes the mean and SD of the relevant experimental data, and the figure panels.

Biomass and metabolites in Col0 (WT) and prr7prr9, with and without exogenous gibberellins (GA)

Luciferase reporter gene assay for circadian period of seedlings in constant light, for Col0 (WT) and prr7prr9, with and without exogenous gibberellins (GA). Supplementary Figure 11f in Chew et al., _in Silico _Plants.

Raw and processed data, together with circadian period analysis and summary statistics, are available from BioDare.ed.ac.uk: choose https://biodare.ed.ac.uk/experiment ("Browse Public Resources" on the Login screen), then you can link to https://biodare.ed.ac.uk/robust/ShowExperiment.action?experimentId=3838, ...

Biomass, leaf number and gas exchange data for Col0 (WT), prr7prr9, and lsf1, compiled from four studies: L&H1-3 and the 'no GA' controls of Gibberellins 1.

Follow-up to the validation experiments on FMv2, testing candidate mechanisms for high malate and fumarate accumulation in the Arabidopsis double mutant prr7prr9 and its parent accession Col.

In this study, 14CO2 labelling was used to test the rate of carbon assimilation in the dark at the end of the subjective night (starting about ZT21), which is indicative of PEPC activity in forming malate, and the subsequent partitioning of this labelled C into various cellular fractions. The short-period ...

Follow-up to the validation experiments on FMv2, testing candidate mechanisms for high malate and fumarate accumulation in the Arabidopsis double mutant prr7prr9 and its parent accession Col.

In this study, thiamine vitamers were quantified to test whether the essential cofactor TDP had altered enzyme activities to affect the malate and fumarate levels, using existing plant samples harvested from am earlier L&H study.

Analysis of carbon metabolites in clock mutants by Anna Flis and Ronan Sulpice, Mark Stitt lab

Excel spreadsheet with data and simulations used to prepare figures for publication, see Metadata sheet for conditions. Data Fresh (not dry) rosette leaf biomass, measured in samples of 5 plants each on multiple days, as mean and SD; Simulation outputs from FMv2 for Col Wild Type plants, and two simulations for prr7prr9 where the mutation affects only starch degradation or both starch degradation and malate/fumarate store mobilisation.

Starch levels in carbon units (not C6) measured on on days ...

Excel workbook with included Read.Me sheet, including FW and DW biomass data derived from files linked elsewhere; a compilation of the rosette area and gas exchange data for every plant measured of the Col, lsf1 and prr7prr9 genotypes; statistical analysis across the experiments; and charts of the compiled data, some of which are presented as figure panels in the 2022 versions.

Biomass data for individual plants at day 35, fresh and dry weights, as well as mean and SD, from study Gibberellins 1

Excel sheet with mean and SD biomass data and charts, individual metabolite replicates, mean, SD and charts Details on Read.ME worksheet

14CO2 assimilation in the night-time, in plants of Col, prr7prr9; Ws, lhycca1 genotypes at 18 and 28 days, and partitioning among cellular fractions.

Excel file with data on levels of thiamine and its metabolites TMP and active cofactor TDP, tested in Col and prr7prr9 samples from study Laurel and Hardy 3. Altered levels of TDP could potentially affect enzymes with TDP cofactors that metabolise malate and fumarate levels, altering their levels in prr7prr9.

Experimental data for Laurel and Hardy 3, in MATLAB binary format.

Simulation data for Laurel and Hardy 2, in MATLAB binary format.

Simulation data for Laurel and Hardy 3, in MATLAB binary format.

Excel spreadsheets for biomass, leaf number, gas exchange and metabolites, including pgm and lhycca1. Key data are for 27-28 day old plants for Col and prr7prr9, analysed for the preprint/publication. Gas exchange data for lhycca1 showed lower Assimilation per unit area than Col, prr7prr9; A in pgm was higher than Col. Metabolite data were also collected for Col and lhycca1 at 18 days, before the lhycca1 flowered, but these are marked as unreliable.

Excel spreadsheet with data and simulations used to prepare figures for publication, see Metadata sheet for conditions. Data Fresh (not dry) rosette leaf biomass, measured in samples of 5 plants each on multiple days, as mean and SD; Simulation outputs from FMv2 for Col Wild Type plants, lsf1, and two simulations for prr7prr9 where the mutation affects only starch degradation or both starch degradation and malate/fumarate store mobilisation.

Starch levels in carbon units (not C6) measured on on ...

For Chew, Seaton et al. Figure 1

Experimental data for Laurel and Hardy 2, in MATLAB binary format.

Model analysis results in binary Matlab format

Mean and SD data for metabolites and biomass, along with metadata used to simulate this experiment.

Complete excel spradsheets for Laurel and Hardy 2, including data for the pgm mutant that were not analysed in the Chew et al. 2017 preprint/publication. Data include fresh and dry biomass, gas exchange, leaf numbers and metabolites in Col0 (WT), prr7prr9, pgm and lsf1 plants. Metabolite data are from plants after 27 days of growth (end of night) and 28 days (end of day and end of night).

A model of the circadian regulation of starch turnover, as published in Seaton, Ebenhoeh, Millar, Pokhilko, "Regulatory principles and experimental approaches to the circadian control of starch turnover", J. Roy. Soc. Interface, 2013. This model is referred to as "Model Variant 2". The other model variants are all available from www.plasmo.ed.ac.uk as stated in the publication. Note that the 'P2011' circadian clock model was modified for this publication (as described), in order to replicate the ...

Matlab model (could not be represented in SBML) from publication with abstract: Clock-regulated pathways coordinate the response of many developmental processes to changes in photoperiod and temperature. We model two of the best-understood clock output pathways in Arabidopsis, which control key regulators of flowering and elongation growth. In flowering, the model predicted regulatory links from the clock to CYCLING DOF FACTOR 1 (CDF1) and FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1) transcription. ...

Framework Model for Arabidopsis vegetative growth, version 2 (FMv2), as described in Chew et al. bioRxiv 2017 (https://doi.org/10.1101/105437; please see linked Article file).

The FMv2 model record on FAIRDOMHub has the following versions, which represent the same FMv2 model: Version 1 is an archive of the github repository of MATLAB code for the Framework Model v2, downloaded from https://github.com/danielseaton/frameworkmodel on 06/02/17. This version was not licensed for further use and was ...

This record includes Matlab and Simile format versions of the Arabidopsis Framework Model version 1, FMv1 (Chew et al, PNAS 2014; http://www.pnas.org/content/early/2014/08/27/1410238111), copied from the PlaSMo resource (www.plasmo.ed.ac.uk), PLM_ID=76. The model description is in the Supplementary Materials of the publication, which should be uploaded somewhere here also but I don't see how to do it.

The FMv1 links the following sub-models:

1. Arabidopsis leaf carbohydrate model (Rasse and ...

Exactly the same as model 243, but uploaded as a file rather than copied from PlaSMo.

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