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基于基因本体和蛋白质相互作用拓扑整合提取的白癜风蛋白质组的参数可靶向性评估方法。

A Parametric Targetability Evaluation Approach for Vitiligo Proteome Extracted through Integration of Gene Ontologies and Protein Interaction Topologies.

出版信息

IEEE/ACM Trans Comput Biol Bioinform. 2019 Nov-Dec;16(6):1830-1842. doi: 10.1109/TCBB.2018.2835459. Epub 2018 May 17.

DOI:10.1109/TCBB.2018.2835459
PMID:29994537
Abstract

Vitiligo is a well-known skin disorder with complex etiology. Vitiligo pathogenesis is multifaceted with many ramifications. A computational systemic path was designed to first propose candidate disease proteins by merging properties from protein interaction networks and gene ontology terms. All in all, 109 proteins were identified and suggested to be involved in the onset of disease or its progression. Later, a composite approach was employed to prioritize vitiligo disease proteins by comparing and benchmarking the properties against standard target identification criteria. This includes sequence-based, structural, functional, essentiality, protein-protein interaction, vulnerability, secretability, assayability, and druggability information. The existing information was seamlessly integrated into efficient pipelines to propose a novel protocol for assessment of targetability of disease proteins. Using the online data resources and the scripting, an illustrative list of 68 potential drug targets was generated for vitiligo. While this list is broadly consistent with the research community's current interest in certain specific proteins, and suggests novel target candidates that may merit further study, it can still be modified to correspond to a user-specific environment, either by adjusting the weights for chosen criteria (i.e., a quantitative approach) or by changing the considered criteria (i.e., a qualitative approach).

摘要

白癜风是一种众所周知的皮肤疾病,其病因复杂。白癜风的发病机制是多方面的,有许多分支。我们设计了一种计算系统路径,首先通过合并蛋白质相互作用网络和基因本体论术语的特性,提出候选疾病蛋白质。总之,确定了 109 种蛋白质,这些蛋白质被认为与疾病的发生或进展有关。之后,我们采用综合方法,通过比较和基准测试针对标准目标识别标准的特性,对白癜风疾病蛋白质进行优先级排序。这包括基于序列、结构、功能、必需性、蛋白质-蛋白质相互作用、脆弱性、可分泌性、可测定性和可用药性信息。将现有信息无缝集成到高效管道中,提出了一种用于评估疾病蛋白质靶向性的新方案。利用在线数据资源和脚本,为白癜风生成了 68 个潜在药物靶点的说明性列表。虽然该列表与研究界目前对某些特定蛋白质的关注广泛一致,并提出了可能值得进一步研究的新的候选靶点,但它仍然可以根据用户特定的环境进行修改,要么通过调整所选标准的权重(即定量方法),要么通过改变考虑的标准(即定性方法)。

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引用本文的文献

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A Study and Analysis of Disease Identification using Genomic Sequence Processing Models: An Empirical Review.使用基因组序列处理模型进行疾病识别的研究与分析:实证综述
Curr Genomics. 2023 Dec 12;24(4):207-235. doi: 10.2174/0113892029269523231101051455.
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A meta-analysis of chemokines in vitiligo: Recruiting immune cells towards melanocytes.一项关于白癜风中趋化因子的荟萃分析:将免疫细胞招募到黑色素细胞中。
Front Immunol. 2023 Feb 24;14:1112811. doi: 10.3389/fimmu.2023.1112811. eCollection 2023.
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The Promising Role of Chemokines in Vitiligo: From Oxidative Stress to the Autoimmune Response.
趋化因子在白癜风中的作用:从氧化应激到自身免疫反应。
Oxid Med Cell Longev. 2022 Jan 19;2022:8796735. doi: 10.1155/2022/8796735. eCollection 2022.
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Mechanisms of melanocyte death in vitiligo.白癜风中黑素细胞死亡的机制。
Med Res Rev. 2021 Mar;41(2):1138-1166. doi: 10.1002/med.21754. Epub 2020 Nov 17.