Conception, modélisation et simulation in silico d'un nanosystème biologique artificiel pour le diagnostic médical

Abstract : The medical diagnosis is traditionally done by examining the clinical symptoms and by searching in samples (blood, urine, biopsies, etc.) for the simultaneous presence (or absence) of biomarkers of the various pathologies considered by the doctor. The search for biomarkers is conducted using large equipments in a specialised laboratory; The results being communicated to the doctor, who will then interpret them by applying a medical diagnostic algorithm.We wanted to combine in a single device, for a given disease, the detection of its biomarkers and an implementation of the appropriate diagnostic algorithm. The presence or absence of a biomarker can be represented by a boolean variable, and the diagnostic algorithm by a complex boolean function whose value indicates the presence of the targeted disease. Our diagnostic device is an artificial biochemical nano-computer in which logical information is represented by metabolites and the computations performed by a synthetic enzymatic network. To build this computer, it has been necessary to establish a theoretical basis of enzymatic logical networks. We then used this theory to define what an enzymatic logic network is, and how it computes correctly the associated boolean function. For modularity and reusability reasons, we decided to design libraries of enzymatic logic gates that implement basic boolean operators, and then to assemble these building blocks to get the complete logic enzymatic network. So, I have designed and developed two software tools, NetGate and NetBuild, which will automatically perform these operations.NetGate creates libraries containing hundreds of enzymatic logic gates obtained from the metabolic networks of living organisms. Before that, it was necessary to manually analyse these metabolic networks in order to extract each logic gate.NetBuild uses a library of logic gates (for example created using NetGate) and assembles them to build circuits that compute a given boolean function. These circuits use specific metabolites for its inputs (for example the biomarkers of a pathology) and produce a readily detectable molecular species (using colorimetry for example).
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Marc Bouffard. Conception, modélisation et simulation in silico d'un nanosystème biologique artificiel pour le diagnostic médical. Bio-informatique [q-bio.QM]. Université Paris-Saclay, 2016. Français. ⟨NNT : 2016SACLS302⟩. ⟨tel-01400244⟩

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