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Identification of Protein-Protein Interaction Bridges for Multiple Sclerosis.

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MOTIVATION Identifying and prioritizing disease-related proteins is an important scientific problem to develop proper treatments. Network science has become an important discipline to prioritize such proteins. Multiple sclerosis (MS), an… Click to show full abstract

MOTIVATION Identifying and prioritizing disease-related proteins is an important scientific problem to develop proper treatments. Network science has become an important discipline to prioritize such proteins. Multiple sclerosis (MS), an autoimmune disease for which there is still no cure, is characterized by a damaging process called demyelination. Demyelination is the destruction of myelin, a structure facilitating fast transmission of neuron impulses, and oligodendrocytes, the cells producing myelin, by immune cells. Identifying the proteins that have special features on the network formed by the proteins of oligodendrocyte and immune cells can reveal useful information about the disease. RESULTS We investigated the most significant protein pairs that we define as bridges among the proteins providing the interaction between the two cells in demyelination, in the networks formed by the oligodendrocyte and each type of two immune cells (i.e., macrophage and T-cell) using network analysis techniques and integer programming. The reason we investigated these specialized hubs was that a problem related to these proteins might impose a bigger damage in the system. We showed that 61% to 100% of the proteins our model detected, depending on parametrization, have already been associated with MS. We further observed the mRNA expression levels of several proteins we prioritized significantly decreased in human peripheral blood mononuclear cells (PBMCs) of MS patients. We therefore present a model, BriFin, which can be used for analyzing processes where interactions of two cell types play an important role. AVAILABILITY BriFin is available at https://github.com/BilkentCompGen/brifin. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

Keywords: interaction; sclerosis; identification protein; immune cells; multiple sclerosis

Journal Title: Bioinformatics
Year Published: 2023

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