The Arabidopsis leaf quantitative atlas: a cellular and subcellular mapping through unified data integration.

Quantitative analyses and models are required to connect a plant's cellular organisation with its metabolism. However, quantitative data are often scattered over multiple studies, and finding such data and converting them into useful information is time-consuming. Consequently, there is a need to centralise the available data and to highlight the remaining knowledge gaps. Here, we present a step-by-step approach to manually extract quantitative data from various information sources, and to unify the data format. First, data from Arabidopsis leaf were collated, checked for consistency and correctness and curated by cross-checking sources. Second, quantitative data were combined by applying calculation rules. They were then integrated into a unique comprehensive, referenced, modifiable and reusable data compendium representing an Arabidopsis reference leaf. This atlas contains the metrics of the 15 cell types found in leaves at the cellular and subcellular levels.

ChloroKB, a cell metabolism reconstruction of the model plant Arabidopsis thaliana.

Can we understand how plant cell metabolism really works? An integrated large-scale modelling of plant metabolism predictive model would make possible to analyse the impact of disturbances in environmental conditions on cellular functioning and diversity of plant-made molecules of interest. ChloroKB, a Web application initially developed for exploration of Arabidopsis chloroplast metabolic network now covers Arabidopsis mesophyll cell metabolism. Interconnected metabolic maps show subcellular compartments, metabolites, proteins, complexes, reactions, and transport. Data in ChloroKB have been structured to allow for mathematical modelling and will be used as a reference for modelling work dedicated to a particular issue.

Peut-on comprendre comment fonctionne réellement le métabolisme des cellules végétales ? Un modèle prédictif intégré à grande échelle du métabolisme des plantes permettrait d'analyser l'impact des perturbations des conditions environnementales sur le fonctionnement cellulaire et la diversité des molécules d'intérêt fabriquées par les plantes. ChloroKB, une application Web initialement développée pour l'exploration du réseau métabolique du chloroplaste d'Arabidopsis, couvre désormais le métabolisme des cellules du mésophylle d'Arabidopsis. Des cartes métaboliques interconnectées décrivent les compartiments subcellulaires, les métabolites, les protéines, les complexes, les réactions et le transport. Les données de ChloroKB ont été structurées pour permettre la modélisation mathématique et seront utilisées comme référence pour les travaux de modélisation consacrés à une question particulière.

A logic-based method to build signaling networks and propose experimental plans.

With the dramatic increase of the diversity and the sheer quantity of biological data generated, the construction of comprehensive signaling networks that include precise mechanisms cannot be carried out manually anymore. In this context, we propose a logic-based method that allows building large signaling networks automatically. Our method is based on a set of expert rules that make explicit the reasoning made by biologists when interpreting experimental results coming from a wide variety of experiment types. These rules allow formulating all the conclusions that can be inferred from a set of experimental results, and thus building all the possible networks that explain these results. Moreover, given an hypothesis, our system proposes experimental plans to carry out in order to validate or invalidate it. To evaluate the performance of our method, we applied our framework to the reconstruction of the FSHR-induced and the EGFR-induced signaling networks. The FSHR is known to induce the transactivation of the EGFR, but very little is known on the resulting FSH- and EGF-dependent network. We built a single network using data underlying both networks. This leads to a new hypothesis on the activation of MEK by p38MAPK, which we validate experimentally. These preliminary results represent a first step in the demonstration of a cross-talk between these two major MAP kinases pathways.

ChloroKB: A Web Application for the Integration of Knowledge Related to Chloroplast Metabolic Network.

Higher plants, as autotrophic organisms, are effective sources of molecules. They hold great promise for metabolic engineering, but the behavior of plant metabolism at the network level is still incompletely described. Although structural models (stoichiometry matrices) and pathway databases are extremely useful, they cannot describe the complexity of the metabolic context, and new tools are required to visually represent integrated biocurated knowledge for use by both humans and computers. Here, we describe ChloroKB, a Web application (http://chlorokb.fr/) for visual exploration and analysis of the Arabidopsis (Arabidopsis thaliana) metabolic network in the chloroplast and related cellular pathways. The network was manually reconstructed through extensive biocuration to provide transparent traceability of experimental data. Proteins and metabolites were placed in their biological context (spatial distribution within cells, connectivity in the network, participation in supramolecular complexes, and regulatory interactions) using CellDesigner software. The network contains 1,147 reviewed proteins (559 localized exclusively in plastids, 68 in at least one additional compartment, and 520 outside the plastid), 122 proteins awaiting biochemical/genetic characterization, and 228 proteins for which genes have not yet been identified. The visual presentation is intuitive and browsing is fluid, providing instant access to the graphical representation of integrated processes and to a wealth of refined qualitative and quantitative data. ChloroKB will be a significant support for structural and quantitative kinetic modeling, for biological reasoning, when comparing novel data with established knowledge, for computer analyses, and for educational purposes. ChloroKB will be enhanced by continuous updates following contributions from plant researchers.

Mapping the follicle-stimulating hormone-induced signaling networks.

Follicle-stimulating hormone (FSH) is a central regulator of male and female reproductive function. Over the last decade, there has been a growing perception of the complexity associated with FSH-induced cellular signaling. It is now clear that the canonical Gs/cAMP/PKA pathway is not the sole mechanism that must be considered in FSH biological actions. In parallel, consistent with the emerging concept of biased agonism, several examples of ligand-mediated selective signaling pathway activation by gonadotropin receptors have been reported. In this context, it is important to gain an integrative view of the signaling pathways induced by FSH and how they interconnect to form a network. In this review, we propose a first attempt at building topological maps of various pathways known to be involved in the FSH-induced signaling network. We discuss the multiple facets of FSH-induced signaling and how they converge to the hormone integrated biological response. Despite of their incompleteness, these maps of the FSH-induced signaling network represent a first step toward gaining a system-level comprehension of this hormone's actions, which may ultimately facilitate the discovery of novel regulatory processes and therapeutic strategies for infertility and non-steroidal contraception.