Abstract
AbstractThe number of genome-scale metabolic models has been rising quickly in recent years, and the scope of their utilization encompasses a broad range of applications from metabolic engineering to biological discovery. However the reconstruction of such models remains an arduous process requiring a high level of human intervention. Their utilization is further hampered by the absence of standardized data and annotation formats and the lack of recognized quality and validation standards.Plants provide a particularly rich range of perspectives for applications of metabolic modeling. We here report the first effort to the reconstruction of a genome-scale model of the metabolic network of the plant Arabidopsis thaliana, including over 2300 reactions and compounds. Our reconstruction was performed using a semi-automatic methodology based on the integration of two public genome-wide databases, significantly accelerating the process. Database entries were compared and integrated with each other, allowing us to resolve discrepancies and enhance the quality of the reconstruction. This process lead to the construction of three models based on different quality and validation standards, providing users with the possibility to choose the standard that is most appropriate for a given application. First, a core metabolic model containing only consistent data provides a high quality model that was shown to be stoichiometrically consistent. Second, an intermediate metabolic model attempts to fill gaps and provides better continuity. Third, a complete metabolic model contains the full set of known metabolic reactions and compounds in Arabidopsis thaliana.We provide an annotated SBML file of our core model to enable the maximum level of compatibility with existing tools and databases. We eventually discuss a series of principles to raise awareness of the need to develop coordinated efforts and common standards for the reconstruction of genome-scale metabolic models, with the aim of enabling their widespread diffusion, frequent update, maximum compatibility and convenience of use by the wider research community and industry.
Highlights
Metabolism is perhaps the best characterized of all molecular interaction networks in biology
Arabidopsis thaliana has been widely used as a model plant, its metabolic network has not been studied in great details and at a large scale
A. thaliana was used as a model plant to study polyamine metabolism, which plays an essential role in stress tolerance (Alcázar et al, 2006), and flavonoid production, which inhibit or stimulate cell proliferation in different human cancer cell lines (Woo et al, 2005)
Summary
Metabolism is perhaps the best characterized of all molecular interaction networks in biology. Arabidopsis thaliana has been widely used as a model plant, its metabolic network has not been studied in great details and at a large scale. More than 170 secondary metabolites from seven different classes have been identified in A. thaliana (D’Auria & Gershenzon, 2005), whose putative functions cover the defense against pathogens and herbivores, UV protection, resistance to oxidative stress, auxin transport, etc. Glucosinolates are known for their benefits to human nutrition and were found to play a fundamental role in the defense response against microbial and fungal pathogens (Clay et al, 2009; Bednarek et al, 2009). A. thaliana was used as a model plant to study polyamine metabolism, which plays an essential role in stress tolerance (Alcázar et al, 2006), and flavonoid production, which inhibit or stimulate cell proliferation in different human cancer cell lines (Woo et al, 2005)
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