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Communication Dans Un Congrès Année : 2019

Target controllability in genetic networks of macrophage activation

Résumé

Macrophage cells play an important role in the Multiple Sclerosis (MS) disease. They are known to participate both to the degen-erative process, myelin destruction, and to the regenerative one, coordinating remyelination. We focused on two activation statesof the macropaghes: ‘alert’, which senses the environment, and ‘pro-inflammatory’, which is entitled of the cell defense againstexternal agents. The correct genetic activation of macrophage phenotypes permits a correct remyelinating response [1], thus thepossibility to steer it towards an healthy state while acting on a limited number of genes (drivers) would be greatly advantageous.We modeled macrophage activation as a network (Figure 1.a), whereNnodes correspond to genes involved in inflammationand directed links correspond to significant influences (inhibition or activation) as retrieved from macrophages.com [2] activationpathways. To enhance interpretation, genes were assigned to four different categories, according to their position inside a cell.We assumed a linear time invariant dynamics and modeled our problem in a target controllability framework [3]. Each gene istested as a driver and target nodes are the 19 genes for which the difference in gene expression between the two states of the macr-pohage cells is most significant(p<0.05)for patients and controls (Figure 1.b). Since computing the rank of the controllabilitymatrix is ill-conditioned for a large network, it was not possible to test all target nodes at the same time. We computed thetargetcontrol centralityas the number of target nodes that can be controlled from a driver node, when the target are chosen as follows:•Step 0: the target set contains the first target node, the target control centrality is zero.•Step 1: build the subgraph to apply the Kalman criterion, nodes accessible from the driver that can reach the target set.•Step 2: check target controllability.–If the configuration is not controllable, discard the last target added to the target set and test the successive one;–else, include the successive target in the target set and increase by one the target control centrality.•Repeat steps 1 and 2 until the last target node is tested.Results showed that the driver nodesIRF7,PRKCDandSTAT1, known to be involved in the MS disease [4] and [5], can controlup to 7 target nodes. Our work is a preliminary step towards the identification of the genes influencing the inflammatory process ofmacrophages, which is a crucial mechanism in the MS’ disease
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Dates et versions

hal-02314001 , version 1 (11-10-2019)

Identifiants

  • HAL Id : hal-02314001 , version 1

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Giulia Bassignana, Jennifer Fransson, Olivier Colliot, Violetta Zujovic, Fabrizio de Vico Fallani. Target controllability in genetic networks of macrophage activation. Netsci 2019, May 2019, Burlington, United States. ⟨hal-02314001⟩
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