Simulation of mitochondrial metabolism using multi-agents system

Metabolic pathways describe chains of enzymatic reactions. Their modelling is a key point to understand living systems. An enzymatic reaction is an interaction between one or several metabolites (substrates) and an enzyme (simple protein or enzymatic complex build of several subunits). In our Mitochondria in Silico Project, MitoScop, we study the metabolism of the mitochondria, an intra-cellular organelle. Many ordinary differential equation models are available in the literature. They well fit experimental results on flux values inside the metabolic pathways, but many parameters are di$\pm$cult to transcribe with such models: localization of enzymes, rules about the reactions scheduler, etc Moreover, a model of a significant part of mitochondrial metabolism could become very complex and contain more than 50 equations. In this context, the multi-agents systems appear as an alternative to model the metabolic pathways. Firstly, we have looked after membrane design. The mitochondria is a particular case because the inner mitochondrial space, ie matricial space, is delimited by two membranes: the inner and the outer one. In addition to matricial enzymes, other enzymes are located inside the membranes or in the inter-membrane space. Analysis of mitochondrial metabolism must take into account this kind of architecture

Estimating landmarks on 2D images of beetle mandibles

Studying links between phenotype/genotype and agricultural practices is one of the main topics in agronomy research. Phenotypes can be characterized by informations like age, sex of animals/plants and more and more often with the help of image analysis of their morphology. From now, getting good quality of images for numerous individuals is easy but that leads to design automatic procedures to replace manual exploration of such amount of images. Several bottlenecks have been identified to analyze automatically images. One of them is segmentation of selected area and/or shapes, and another well-known one is setting automatically morphometric landmarks. Landmarks are points on the object which can be used to identify or to classify the objects. It exists a lot of methods to experiment landmarks setting, depending on the image contents. This work has been initiated by using the article of Palaniswamy et al. "Automatic identification of landmarks in digital images"[6]. They proposed a method based on calculus of a probabilistic Hough transform coupling to a template matching algorithm. They applied their method to the Drosophilia wings. In our study, we have gotten a set of 291 beetles . For each one 2D images of 5 different parts of their anatomy have been taken: mandibles left and right, head, pronotum and elytra. The first part of the project was to test how the Palaniswamy’s method could be used to analyze them. We have implemented all the required algorithms to compute positions of mandibles landmarks and compared the obtained results to landmarks which have been manually set by biologists. We will see that even positions automatically obtained are not fully precised, if we used centroid size to characterize mandibles, the size computed from automatic landmarks is closed to this one computed from the manual ones. Future works will focus on definition of a semi-landmarks procedure which would add some features as the measure of the curve between two landmarks

Comparison between elementary flux modes analysis and 13C-metabolic fluxes measured in bacterial and plant cells

<p>Abstract</p> <p>Background</p> <p>¹³C metabolic flux analysis is one of the pertinent ways to compare two or more physiological states. From a more theoretical standpoint, the structural properties of metabolic networks can be analysed to explore feasible metabolic behaviours and to define the boundaries of steady state flux distributions. Elementary flux mode analysis is one of the most efficient methods for performing this analysis. In this context, recent approaches have tended to compare experimental flux measurements with topological network analysis.</p> <p>Results</p> <p>Metabolic networks describing the main pathways of central carbon metabolism were set up for a bacteria species (<it>Corynebacterium glutamicum</it>) and a plant species (<it>Brassica napus</it>) for which experimental flux maps were available. The structural properties of each network were then studied using the concept of elementary flux modes. To do this, coefficients of flux efficiency were calculated for each reaction within the networks by using selected sets of elementary flux modes. Then the relative differences - reflecting the change of substrate <it>i.e</it>. a sugar source for <it>C</it>. <it>glutamicum </it>and a nitrogen source for <it>B</it>. <it>napus </it>- of both flux efficiency and flux measured experimentally were compared. For both organisms, there is a clear relationship between these parameters, thus indicating that the network structure described by the elementary flux modes had captured a significant part of the metabolic activity in both biological systems. In <it>B</it>. <it>napus</it>, the extension of the elementary flux mode analysis to an enlarged metabolic network still resulted in a clear relationship between the change in the coefficients and that of the measured fluxes. Nevertheless, the limitations of the method to fit some particular fluxes are discussed.</p> <p>Conclusion</p> <p>This consistency between EFM analysis and experimental flux measurements, validated on two metabolic systems allows us to conclude that elementary flux mode analysis could be a useful tool to complement ¹³C metabolic flux analysis, by allowing the prediction of changes in internal fluxes before carbon labelling experiments.</p

Modelling of complex biological systems in the context of genomics: an account of a multidisciplinary thematic seminar held in Montpellier (France) in April 2005

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Modélisation et simulation multi-agents de phénomènes d'oxydo-réduction (application au complexe III de la chaîne respiratoire)

Les mouvements de larges sous-unités protéiques sont très importants dans la liaison des substrats et les propriétés catalytiques des enzymes. Le but de notre étude a été de combiner la modélisation des réactions d'oxydo-réduction et les changements de conformations des complexes enzymatiques redox afin de décrire la dynamique réactionnelle de ces complexes. Nous avons réutilisé des algorythmes précédemment décrits dans la littérature afin de déterminer les changements conformationnels au sein des complexes redox. Nous avons ensuite développé un Système Multi-Agent permettant la simulation des activités redox de ces complexes. Nous avons appliqué notre approche à l'étude du complexe III de la Chaine Respiratoire Mitochondriale. Notre modèle nous permet de retrouver le onctionnement normal du complexe III lié à la dynamique de ces réactions redox et de ces mouvements internes.Because movements of large protein structures are key components in ligand docking and enzymatic catalysis, our aim was to combine modeling of the redox reactions and modeling of the conformational changes of enzymatic oxydoreduction complex in order to describe their dynamical functioning. We decided to reused previously described algorithms in order to uncover the conformational changes of redox complexes. We have then developed a Multi-Agent System to simulate the redox activiities of these complexes. We have applied our method to the complex III of the Mitochondrial Respiratory Chain. With this modeling we are able to find the normal functioning of the complex III as a consequence of the reaction mechanisms taking into account the tridimensional structure of the complex and its conformational changes.BORDEAUX2-BU Santé (330632101) / SudocBREST-ENIB (290192307) / SudocSudocFranceF

Architecture d'un système d'aide au diagnostic médical (application en rhumatologie inflammatoire)

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Matching ostraca fragments using a siamese neural network

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