Department of Computer Engineering, Bilkent University, Ankara, Turkey.
Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, Turkey.
Bioinformatics. 2023 Apr 3;39(4). doi: 10.1093/bioinformatics/btad175.
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, 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.
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%-100% of the proteins our model detected, depending on parameterization, have already been associated with multiple sclerosis. We further observed the mRNA expression levels of several proteins we prioritized significantly decreased in human peripheral blood mononuclear cells of multiple sclerosis patients. We therefore present a model, BriFin, which can be used for analyzing processes where interactions of two cell types play an important role.
BriFin is available at https://github.com/BilkentCompGen/brifin.
识别和优先考虑与疾病相关的蛋白质是开发适当治疗方法的重要科学问题。网络科学已成为优先考虑此类蛋白质的重要学科。多发性硬化症是一种自身免疫性疾病，目前尚无治愈方法，其特征是一种称为脱髓鞘的破坏性过程。脱髓鞘是由免疫细胞破坏髓鞘，即促进神经元冲动快速传递的结构，以及产生髓鞘的少突胶质细胞。识别在少突胶质细胞和免疫细胞的蛋白质形成的网络上具有特殊特征的蛋白质，可以揭示有关该疾病的有用信息。
我们使用网络分析技术和整数规划研究了在脱髓鞘过程中两种细胞之间相互作用的蛋白质形成的网络中，最显著的蛋白质对（我们定义为桥梁）。我们研究这些特殊的枢纽是因为与这些蛋白质相关的问题可能会对系统造成更大的损害。我们表明，我们的模型检测到的蛋白质中有 61%-100%（具体取决于参数化）已经与多发性硬化症有关。我们还观察到我们优先考虑的几种蛋白质的 mRNA 表达水平在多发性硬化症患者的人外周血单核细胞中显著降低。因此，我们提出了一个模型 BriFin，可用于分析两种细胞类型相互作用起重要作用的过程。
BriFin 可在 https://github.com/BilkentCompGen/brifin 上获得。
