A modelling portal for the UK plant systems biology community

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

This project is all about plant growth models. Here, the word 'model' does not refer to a physical object but instead means a mathematical way of representing something. This kind of model consists of a series of mathematical equations which can be solved, normally using a computer. By feeding these equations with values for factors like temperature, amount of nitrogen available and light energy that plants can capture, the models make it possible to predict how a plant will grow. Many of the models available are for crop plants, and they can give estimates of how much a crop will produce, whether it is a wheat plant yielding grain, a tree growing new wood, or a pasture providing grass to feed animals. Some of the more complicated ones also represent interactions between plants and other species, such as bacteria and fungi which improve or reduce nutrient uptake by plant roots, or leaf-eating herbivores. Historically, these models work at the level of a whole plant, a farmer's field or even a landscape, because it has been most straightforward to collect data at these levels. Modelling plant growth, an area of research which has flourished for several decades, is one in which the UK has been especially strong, but which is not well known among modern molecular scientists. In the new era of 'systems biology' research, scientists are able to capture large amounts of data about processes that happen on a much finer scale - an individual leaf or root, for example, or even within a single cell. The challenge is to use this mass of information to predict how a plant's genetic makeup controls the way it grows and interacts with its environment. It is becoming clear that many of the mathematical techniques needed to make this possible are the same as those used by the crop modellers. The aim of the present project is to make existing crop models available to systems biology researchers via the Internet in a user-friendly way that is independent of any particular computer software. This means that systems biologists can adapt models for their own use, and connect them with other models that work at the cell level. We want to develop a portal, a one-stop Internet shop for the models themselves, examples of how they have been applied, and explanations detailed enough to allow other people to adopt them. We will also provide a forum so that the community can add comments and suggestions for further development, and help each other in using these and other models in the future. In addition to plant systems biology experts, the portal will be of use to crop scientists and to policy-makers. Predicted climate change will mean that our current crops will perform differently in the future - the models will help predict whether the difference will be beneficial or cause loss of yield or failure of crops. They will also aid researchers and breeders in developing crops for new uses, such as bioenergy. Some models have the capability to predict the behaviour of whole ecosystems, such as forests, under changing conditions. Models are important for the future of plant science research, agriculture and the environment and it is important to make them as widely accessible and usable as possible / this is the purpose of our project.

Technical Summary

The project will develop a portal to make available, in open-source format, plant growth models relevant to the needs of the UK systems biology and crop science communities. A Wiki will allow researchers from all fields to provide input on the models. Seven existing models have already been selected for implementation and at least 3 others will be chosen through discussion with the community. Models available in a range of formats and programming languages will be represented in an open-standard declarative XML format, using an established modelling environment. A declarative language allows models to be displayed in various ways and efficiently makes model metadata available automatically. The XML generated for each model can be run through one of several code-generators (some already implemented), allowing users flexibility in the language and computational platform used for implementation. We will provide annotated examples of typical output for each model and devise simulations and analysis for publication and dissemination on the portal. Demonstration results will use the high-level models developed here and also models at other scales. The portal will integrate the models with software tools used by systems biologists and will make models available to users at external sites, via the Systems Biology Software Infrastructure at the Centre for Systems Biology Edinburgh. To extend the Systems Biology Markup Language to represent plant growth models not expressible in biochemical-pathway terms we will collaborate with Dr N le Novère (European Bioinformatics Institute), who is responsible for the BioModels portal. Further links between the project participants and the SBML community, other UK Centres for Integrated Systems Biology and EBI will keep the portal's development abreast of international standards development, including plant and trait ontologies, and allow the project staff to provide input to the development of later model exchange standards.

Publications

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Andrew Millar (Author) (2009) Development of a web portal for plant models in Journal of Agricultural Science

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Chew YH (2014) Multiscale digital Arabidopsis predicts individual organ and whole-organism growth. in Proceedings of the National Academy of Sciences of the United States of America

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Davey C (2009) PlaSMo: Making existing plant and crop mathematical models available to plant systems biologists in Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology

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Muetzelfeldt, R (2009) Development of a web portal for plant models in Journal of Agricultural Science

 
Description Crop and other plant growth models, at scales ranging from the cellular to the ecosystem, were safeguarded for the future by converting them to a declarative format and making them available to the plant systems biology and crop communities in XML format.

A public-access web portal (http://www.plasmo.ed.ac.uk) allows users to display and run the models, obtain documentation about them, and download detailed descriptions of the model conversion and validation processes to facilitate their own modelling activities The project has been publicised to systems biologists, crop scientists and agricultural scientists
throughout the UK, as well as to international audiences, and has attracted widespread interest.

The reiimplemented models are already being used by staff of the BBSRC Bioenergy Centre and CSBE (now SynthSys) in Edinburgh.
Exploitation Route Models from PlaSMo provide the components for modular, multi-scale models in future, as demonstrated in the Arabidopsis Framework Model of Chew et al. PNAS 2014
Sectors Agriculture, Food and Drink,Environment

URL http://www.plasmo.ed.ac.uk
 
Description The online portal arising from this joint award is being used by several other projects to store and disseminate their mathematical models: Centre for Systems Biology at Edinburgh (now SynthSys), the ROBuST Systems Biology project, and the EU TiMet project. For the latter two projects, the existence of the PlaSMo portal was helpful in acquiring the funding, so PlaSMo is a valuable piece of research infrastructure.
 
Title Mathematical model of the Arabidopsis circadian clock: the P2011 model 
Description [from the record in PlaSMo] This model is termed P2011 and derives from the article: The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops. Alexandra Pokhilko, Aurora Piñas Fernández, Kieron D Edwards, Megan M Southern, Karen J Halliday & Andrew J Millar Mol. Syst. Biol. 2012; 8: 574, published 6 March 2012. Link The model describes the circuit depicted in Fig. 1 of the paper (GIF attached). It updates the Pokhilko et al. 2010 model (termed P2010), PLM_6, by including: the Evening Complex genes (ELF4, ELF3, LUX), light-regulated degradation of ELF3 by COP1, TOC1 as a repressor rather than an activator of LHY/CCA1.These changes allowed the removal of hypothetical components TOC1mod (or X) and Y from the earlier models. They also reveal that the central loop of the model is a triple-repressor ring oscillator, or 'repressilator' (illustrated in Fig. 8, GIF attached). Compared to the model version submitted to the Biomodels database, this version slightly alters the names of some variables and uses an SBML AssignmentRule for the light input. This will facilitate the use of a generic SBML StepFunction to better describe the light-dark cycle, in a subsequent version of this model. 
Type Of Material Computer model/algorithm 
Year Produced 2012 
Provided To Others? Yes  
Impact Further publications and model development 
 
Title Mathematical model of the clock gene circuit in the alga Ostreococcus tauri 
Description Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable environmental changes. Detailed understanding of the circadian network of higher plants, such as Arabidopsis thaliana, is hampered by the high number of partially redundant genes. However, the picoeukaryotic alga Ostreococcus tauri, which was recently shown to possess a small number of non-redundant clock genes, presents an attractive alternative target for detailed modelling of circadian clocks in the green lineage. Based on extensive time-series data from in vivo reporter gene assays, we developed a model of the Ostreococcus clock as a feedback loop between the genes TOC1 and CCA1. The model reproduces the dynamics of the transcriptional and translational reporters over a range of photoperiods. Surprisingly, the model is also able to predict the transient behaviour of the clock when the light conditions are altered. Despite the apparent simplicity of the clock circuit, it displays considerable complexity in its response to changing light conditions. Systematic screening of the effects of altered day length revealed a complex relationship between phase and photoperiod, which is also captured by the model. The complex light response is shown to stem from circadian gating of light-dependent mechanisms. This study provides insights into the contributions of light inputs to the Ostreococcus clock. The model suggests that a high number of light-dependent reactions are important for flexible timing in a circadian clock with only one feedback loop. 
Type Of Material Computer model/algorithm 
Year Produced 2011 
Provided To Others? Yes  
Impact Research funding and publications 
URL http://www.plasmo.ed.ac.uk
 
Title Model for starch polymerisation and degradation in the alga, Ostreococcus tauri. 
Description BACKGROUND: The storage of photosynthetic carbohydrate products such as starch is subject to complex regulation, effected at both transcriptional and post-translational levels. The relevant genes in plants show pronounced daily regulation. Their temporal RNA expression profiles, however, do not predict the dynamics of metabolite levels, due to the divergence of enzyme activity from the RNA profiles.Unicellular phytoplankton retains the complexity of plant carbohydrate metabolism, and recent transcriptomic profiling suggests a major input of transcriptional regulation. RESULTS: We used a quasi-steady-state, constraint-based modelling approach to infer the dynamics of starch content during the 12 h light/12 h dark cycle in the model alga Ostreococcus tauri. Measured RNA expression datasets from microarray analysis were integrated with a detailed stoichiometric reconstruction of starch metabolism in O. tauri in order to predict the optimal flux distribution and the dynamics of the starch content in the light/dark cycle. The predicted starch profile was validated by experimental data over the 24 h cycle. The main genetic regulatory targets within the pathway were predicted by in silico analysis. CONCLUSIONS: A single-reaction description of starch production is not able to account for the observed variability of diurnal activity profiles of starch-related enzymes. We developed a detailed reaction model of starch metabolism, which, to our knowledge, is the first attempt to describe this polysaccharide polymerization while preserving the mass balance relationships. Our model and method demonstrate the utility of a quasi-steady-state approach for inferring dynamic metabolic information in O. tauri directly from time-series gene expression data. 
Type Of Material Computer model/algorithm 
Year Produced 2011 
Provided To Others? Yes  
Impact Further publications, model development in Arabidopsis. 
 
Title The Plant Systems Modelling portal, PlaSMo 
Description The Plant Systems Modelling portal, PlaSMo, meets a need identified as a priority by the plant systems biology community during a workshop on Succeeding in Plant Systems Biology organised by BBSRC and GARNet, the Genomic Arabidopsis Resource Network, in July 2005. Existing types of models used by systems biologists, which are suitable for representing metabolic pathways and genetic regulatory networks at the subcellular and cellular level, lack the properties necessary for modelling the growth and environmental responses of whole plants. To address this concern, a further meeting bringing together researchers from the systems biology, bioinformatics and agro-ecological modelling communities (Interfacing Systems Biology with Crop and Ecosystem Modelling; Swindon, March 2006) was jointly organised by GARNet and crop scientists from IGER (now IBERS) Aberystwyth. There was a strong consensus at the meeting that existing crop models, some produced as long ago as the 1960s and 70s, together with more recent approaches such as L-systems modelling of plant morphogenesis, have enormous potential to contribute to plant systems biology. However, it was acknowledged that much expertise in crop modelling has suffered attrition in the last two decades, and that many of the models developed by these experts were in danger of being lost A key recommendation in the final report of the workshop was therefore the development of: "a Plant Specific Model Repository - a central resource of current plant based models for others to use and test." PlaSMo is the response. 
Type Of Material Database/Collection of data 
Year Produced 2010 
Provided To Others? Yes  
Impact Multiple subsequent projects and publications have used this resource. 
URL http://www.plasmo.ed.ac.uk