Our understanding of the complex, transcriptional feedback loops in the circadian clock mechanism has depended upon quantitative, timeseries data from disparate sources. We measure clock gene RNA profiles in Arabidopsis thaliana seedlings, grown with or without exogenous sucrose, or in soil-grown plants and in wild-type and mutant backgrounds. The RNA profiles were strikingly robust across the experimental conditions, so current mathematical models are likely to be broadly applicable in leaf tissue. In addition to providing reference data, unexpected behaviours included co-expression of PRR9 and ELF4, and regulation of PRR5 by GI. Absolute RNA quantification revealed low levels of PRR9 transcripts (peak approx. 50 copies cell(-1)) compared with other clock genes, and threefold higher levels of LHY RNA (more than 1500 copies cell(-1)) than of its close relative CCA1. The data are disseminated from BioDare, an online repository for focused timeseries data, which is expected to benefit mechanistic modelling. One data subset successfully constrained clock gene expression in a complex model, using publicly available software on parallel computers, without expert tuning or programming. We outline the empirical and mathematical justification for data aggregation in understanding highly interconnected, dynamic networks such as the clock, and the observed design constraints on the resources required to make this approach widely accessible.
SEEK ID: https://fairdomhub.org/publications/306
PubMed ID: 26468131
Projects: Millar group
Publication type: Not specified
Journal: Open Biol
Citation: Open Biol. 2015 Oct;5(10). pii: 150042. doi: 10.1098/rsob.150042.
Date Published: 16th Oct 2015
Registered Mode: Not specified
Authors: A. Flis, A. P. Fernandez, T. Zielinski, V. Mengin, R. Sulpice, K. Stratford, A. Hume, A. Pokhilko, M. M. Southern, D. D. Seaton, H. G. McWatters, M. Stitt, K. J. Halliday, A. J. Millar
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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/0000-0003-1756-3654SynthSys 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 models in this record were published in Flis et al. Royal Society Open Biology 2015. Their original IDs in the PlaSMo resource and IDs in Biomodels are given below. Please select files for download from the 'Related Items' list or the object tree/graph, below. 'SUBMITTED' is the original model version; 'SIMPLIFIED' removes SBML elements that were incompatible with SloppyCell software.
Original model: Arabidopsis clock model P2011.1.1 from Pokhilko et al. Mol Syst. Biol. 2012, ...
Submitter: BioData SynthSys
Investigation: Millar, Andrew (ex-PlaSMo models)
Assays: Arabidopsis clock model P2011.1.2 - PLM_71, version 1, Arabidopsis clock model P2011.2.1 - PLM_71, version 2
Snapshots: No snapshots
RNA timeseries data from TiMet for clock genes in prr7 prr9 and Col wild-type plants under 12L:12D cycle and LL
Submitter: Andrew Millar
Assay type: Gene Expression Profiling
Technology type: qRT-PCR
Investigation: Prediction and analysis of phenotypes in the Ar...
Organisms: Arabidopsis thaliana : Col-0 wild type (wild-type / wild-type), Arabidopsis thaliana : prr7-3 prr9-1 (T-DNA insertion PRR9;T-DNA insertion PRR7 / 28h circadian rhythm), Arabidopsis thaliana
SOPs: No SOPs
Data files: TiMet WP1.1 qRT-PCR LD to LL and DD
Snapshots: No snapshots
The models in this record were published in Flis et al. Royal Society Open Biology 2015. They will be submitted to Biomodels when we have a PubMed ID for the paper.
Original model: Arabidopsis clock model P2011.1.1 from Pokhilko et al. Mol Syst. Biol. 2012, http://dx.doi.org/10.1038/msb.2012.6
Published version is Biomodels ID 00412, http://www.ebi.ac.uk/compneur-srv/biomodels-main/BIOMD0000000412 Also public in Plasmo as PLM_64, with several versions, http://www.plasmo.ed.ac.uk/plasmo/models/model.shtml?accession=PLM_64 ...
Submitter: BioData SynthSys
Biological problem addressed: Gene Regulatory Network
Investigation: Millar, Andrew (ex-PlaSMo models)
Organisms: Arabidopsis thaliana
Models: Arabidopsis clock model P2011.2.1 - PLM_71, ver..., Arabidopsis clock model P2011.2.1 - PLM_71, ver...
SOPs: No SOPs
Data files: SBSI output from optimisation 26-30 July 2013, ..., Unpacked SBSI optimisation results, PLM_71_ 2
Snapshots: No snapshots
RNA levels for control amplicons and multiple clock genes in 2 WT (Col, Ws) and 5 clock mutants of Arabidopsis, in biological duplicates, from three conditions: Diurnal cycle (12L/12D), Extended night (DD), Extended light (LL), harvested every 2 hours. Numbers are in transcript copy per cell, obtained assuming 1 g FW contains 25000000 cells. Comments: Data from LD are concateneted with DD and LL for better visualization. Toc1-101 (col-0) gi-201 (col-0) prr7-3 prr9-1 (col-0) , lhy cca1 (ws) elf3-4 ...
Creator: Andrew Millar
Submitter: Andrew Millar
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 ...
Creators: Andrew Millar, Uriel Urquiza Garcia
Submitter: Andrew Millar
Investigations: Absolute units in Arabidopsis clock models up t... and 1 hidden item
Studies: Rescaling the P2011 model to match RNA data and 1 hidden item
Assays: TiMet RNA timeseries data and starting models and 1 hidden item
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 ...
Creators: Andrew Millar, Uriel Urquiza Garcia
Submitter: Andrew Millar
Investigations: Absolute units in Arabidopsis clock models up t... and 1 hidden item
Studies: Rescaling the P2011 model to match RNA data and 1 hidden item
Assays: TiMet RNA timeseries data and starting models and 1 hidden item
Data file for PLaSMo accesssion ID PLM_71, version 2
Creators: BioData SynthSys, Andrew Millar, Andrew Millar
Submitter: BioData SynthSys
Investigations: Millar, Andrew (ex-PlaSMo models)
Data file for PLaSMo accesssion ID PLM_71, version 2
Creators: BioData SynthSys, Andrew Millar, Andrew Millar
Submitter: BioData SynthSys
Investigations: Millar, Andrew (ex-PlaSMo models)
Simplified model file for PLaSMo accession ID PLM_71, version 2 (use simplified if your software cannot read the file, e.g. Sloppy Cell)
Creators: BioData SynthSys, Andrew Millar, Andrew Millar
Submitter: BioData SynthSys
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Not specified
Organism: Arabidopsis thaliana
Investigations: Millar, Andrew (ex-PlaSMo models)
Originally submitted model file for PLaSMo accession ID PLM_71, version 2
Creators: BioData SynthSys, Andrew Millar, Andrew Millar
Submitter: BioData SynthSys
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Millar, Andrew (ex-PlaSMo models)
Originally submitted model file for PLaSMo accession ID PLM_71, version 1
Creators: BioData SynthSys, Andrew Millar, Andrew Millar
Submitter: BioData SynthSys
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Not specified
Organism: Arabidopsis thaliana
Investigations: Millar, Andrew (ex-PlaSMo models)
Originally submitted model file for PLaSMo accession ID PLM_1041, version 1
Creators: BioData SynthSys, Andrew Millar, Andrew Millar
Submitter: BioData SynthSys
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Not specified
Organism: Arabidopsis thaliana
Investigations: Millar, Andrew (ex-PlaSMo models)
Simplified model file for PLaSMo accession ID PLM_1041, version 1 (use simplified if your software cannot read the file, e.g. Sloppy Cell)
Creators: BioData SynthSys, Andrew Millar, Andrew Millar
Submitter: BioData SynthSys
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: Not specified
Organism: Arabidopsis thaliana
Investigations: Millar, Andrew (ex-PlaSMo models)
Arabidopsis clock model P2011.6.1 SBML imported into Copasi 4.8 and saved as native Copasi file.
Creators: Andrew Millar, Uriel Urquiza Garcia, Kevin Stratford, EPCC
Submitter: Andrew Millar
Model type: Ordinary differential equations (ODE)
Model format: Copasi
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Millar, Andrew (ex-PlaSMo models)
The P2011.3.1 SBML model imported into Copasi v4.8, saved as native Copasi file
Creators: Andrew Millar, Uriel Urquiza Garcia, Kevin Stratford, EPCC
Submitter: Andrew Millar
Model type: Ordinary differential equations (ODE)
Model format: Copasi
Environment: Copasi
Organism: Arabidopsis thaliana
Investigations: Millar, Andrew (ex-PlaSMo models)
Exactly the same as model 243, but uploaded as a file rather than copied from PlaSMo.
Creator: Andrew Millar
Submitter: Andrew Millar
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: JWS Online
Organism: Arabidopsis thaliana
Investigations: Prediction and analysis of phenotypes in the Ar...
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
Creator: Andrew Millar
Submitter: Andrew Millar
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: JWS Online
Organism: Arabidopsis thaliana
Investigations: Absolute units in Arabidopsis clock models up t..., Prediction and analysis of phenotypes in the Ar...
Studies: Construction of Framework Model version 2 (FMv2), Rescaling the P2011 model to match RNA data
Assays: Simulating clock gene expression with model P20..., TiMet RNA timeseries data and starting models