Reconstruction and clustering with graph optimization and priors on gene networks and images

Abstract : The discovery of novel gene regulatory processes improves the understanding of cell phenotypicresponses to external stimuli for many biological applications, such as medicine, environmentor biotechnologies. To this purpose, transcriptomic data are generated and analyzed from mi-croarrays or more recently RNAseq experiments. For each gene of a studied organism placed indifferent living conditions, they consist in a sequence of genetic expression levels. From thesedata, gene regulation mechanisms can be recovered by revealing topological links encoded ingeometric graphs. In regulatory graphs, nodes correspond to genes. A link between two nodesis identified if a regulation relationship exists between the two corresponding genes. Such net-works are called Gene Regulatory Networks (GRNs). Their construction as well as their analysisremain challenging despite the large number of available inference methods.In this thesis, we propose to address this network inference problem with recently developedtechniques pertaining to graph optimization. Given all the pairwise gene regulation informa-tion available, we propose to determine the presence of edges in the final GRN by adoptingan energy optimization formulation integrating additional constraints. Either biological (infor-mation about gene interactions) or structural (information about node connectivity) a priorihave been considered to reduce the space of possible solutions. Different priors lead to differentproperties of the global cost function, for which various optimization strategies can be applied.The post-processing network refinements we proposed led to a software suite named BRANE for“Biologically-Related A priori for Network Enhancement”. For each of the proposed methodsBRANE Cut, BRANE Relax and BRANE Clust, our contributions are threefold: a priori-based for-mulation, design of the optimization strategy and validation (numerical and/or biological) onbenchmark datasets.In a ramification of this thesis, we slide from graph inference to more generic data processingsuch as inverse problems. We notably invest in HOGMep, a Bayesian-based approach using aVariation Bayesian Approximation framework for its resolution. This approach allows to jointlyperform reconstruction and clustering/segmentation tasks on multi-component data (for instancesignals or images). Its performance in a color image deconvolution context demonstrates bothquality of reconstruction and segmentation. A preliminary study in a medical data classificationcontext linking genotype and phenotype yields promising results for forthcoming bioinformaticsadaptations.
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Aurélie Pirayre. Reconstruction and clustering with graph optimization and priors on gene networks and images. Signal and Image Processing. Université Paris-Est, 2017. English. ⟨NNT : 2017PESC1170⟩. ⟨tel-02067269⟩

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