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追踪人类口腔微生物组蛋白-蛋白相互作用的功能意义。

Tracking the functional meaning of the human oral-microbiome protein-protein interactions.

机构信息

Universidade Católica Portuguesa, Faculty of Dental Medicine, Center for Interdisciplinary Research in Health (CIIS), Viseu, Portugal.

出版信息

Adv Protein Chem Struct Biol. 2020;121:199-235. doi: 10.1016/bs.apcsb.2019.11.014. Epub 2020 Jan 16.

DOI:10.1016/bs.apcsb.2019.11.014
PMID:32312422
Abstract

The interactome - the network of protein-protein interactions (PPIs) within a cell or organism - is technically difficult to assess. Bioinformatic tools can, not only, identify potential PPIs that can be later experimentally validated, but also be used to assign functional meaning to PPIs. Saliva's potential as a non-invasive diagnostic fluid is currently being explored by several research groups. But, in order to fully attain its potential, it is necessary to achieve the full characterization of the mechanisms that take place within this ecosystem. The onset of omics technologies, and specifically of proteomics, delivered a huge set of data that is largely underexplored. Quantitative information relative to proteins within a given context (for example a given disease) can be used by computational algorithms to generate information regarding PPIs. These PPIs can be further analyzed concerning their functional meaning and used to identify potential biomarkers, therapeutic targets, defense and pathogenicity mechanisms. We describe a computational pipeline that can be used to identify and analyze PPIs between human and microbial proteins. The pipeline was tested within the scenario of human PPIs of systemic (Zika Virus infection) and of oral conditions (Periodontal disease) and also in the context of microbial interactions (Candida-Streptococcus) and showed to successfully predict functionally relevant PPIs. The pipeline can be applied to different scientific areas, such as pharmacological research, since a functional meaningful PPI network can provide insights on potential drug targets, and even new uses for existing drugs on the market.

摘要

细胞或生物体中的蛋白质-蛋白质相互作用(PPIs)的互作组(interactome)技术上难以评估。生物信息学工具不仅可以识别潜在的 PPI,这些 PPI 可以进一步通过实验验证,还可以用于为 PPI 分配功能意义。目前,几个研究小组正在探索唾液作为非侵入性诊断液的潜力。但是,为了充分发挥其潜力,有必要充分描述发生在这个生态系统中的机制的全面特征。组学技术的出现,特别是蛋白质组学,提供了大量尚未充分探索的大量数据。与给定上下文中(例如,给定疾病)的蛋白质相关的定量信息可以由计算算法用于生成有关 PPI 的信息。这些 PPI 可以进一步针对其功能意义进行分析,并用于识别潜在的生物标志物、治疗靶点、防御和致病性机制。我们描述了一种可以用于识别和分析人类和微生物蛋白质之间的 PPI 的计算管道。该管道在系统性(寨卡病毒感染)和口腔条件(牙周病)的人类 PPI 情景以及微生物相互作用(念珠菌-链球菌)的背景下进行了测试,并成功地预测了具有功能相关性的 PPI。该管道可以应用于不同的科学领域,如药理学研究,因为功能意义上的 PPI 网络可以提供有关潜在药物靶点的见解,甚至可以为市场上现有的药物提供新的用途。

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