Predicting and exploring network components involved in pathogenesis in the malaria parasite via novel subnetwork alignments.
Predicting and exploring network components involved in pathogenesis in the malaria parasite via novel subnetwork alignments.
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DOI：
10.1186/1752-0509-9-s4-s1
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发表时间：
2015
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Cai H;Lilburn TG;Hong C;Gu J;Kuang R;Wang Y
疟疾是一种主要的健康威胁，影响着世界40%以上的人口。世界卫生组织发布的最新报告估计，仅2012年就有约2.07亿例疟疾感染病例，约62.7万人死亡。在过去的十年中，新的治疗目标已经确定，并在不同阶段的表征，由于新兴的组学为基础的技术。然而，疟疾发病机制在很大程度上仍然未知。在本文中，我们采用了一种新的邻域子网络对齐方法来识别网络组件，可能参与发病机制。我们的基于模块的子网络比对方法确定了24个功能同源的发病机制相关的蛋白质在疟原虫恶性疟原虫，使用蛋白质相互作用网络在大肠杆菌作为参考。这24种蛋白质中有18种与418种其他蛋白质相关，这些蛋白质与DNA复制、转录调节、翻译、信号传导、代谢、细胞周期调节以及细胞粘附和进入宿主有关。子网络比对和随后的蛋白质-蛋白质关联网络挖掘预测了一组可能参与寄生虫发育和寄生虫-宿主相互作用的疟疾蛋白质，为寄生虫发病机制和毒力开辟了新的系统水平视图。
Malaria is a major health threat, affecting over 40% of the world's population. The latest report released by the World Health Organization estimated about 207 million cases of malaria infection, and about 627,000 deaths in 2012 alone. During the past decade, new therapeutic targets have been identified and are at various stages of characterization, thanks to the emerging omics-based technologies. However, the mechanism of malaria pathogenesis remains largely unknown. In this paper, we employ a novel neighborhood subnetwork alignment approach to identify network components that are potentially involved in pathogenesis. Our module-based subnetwork alignment approach identified 24 functional homologs of pathogenesis-related proteins in the malaria parasite P. falciparum, using the protein-protein interaction networks in Escherichia coli as references. Eighteen out of these 24 proteins are associated with 418 other proteins that are related to DNA replication, transcriptional regulation, translation, signaling, metabolism, cell cycle regulation, as well as cytoadherence and entry to the host. The subnetwork alignments and subsequent protein-protein association network mining predicted a group of malarial proteins that may be involved in parasite development and parasite-host interaction, opening a new systems-level view of parasite pathogenesis and virulence.