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小编导读
在大脑-肠道的双向通讯系统中,肠道微生物是一项重要的载体,影响和干预神经、内分泌和免疫系统的信号传递途径。因此,“肠脑轴”被进一步延伸为“微生物-肠-脑(MGB)轴”。MGB轴在神经精神病学领域引起了研究者们极大的兴趣与关注。来自荷兰阿姆斯特丹自由大学的黄智生教授、刘婷博士等人在期刊Journal of Artificial Intelligence of Medical Sciences(eISSN 2666-1470)上发表了题为“Exploring the Microbiota-Gut-Brain Axis for Mental Disorders with Knowledge Graphs”的文章,用知识图谱技术探索肠道微生物通过调节神经递质而影响精神健康,由此进一步研究微生物-肠-脑轴与精神疾病的关系。
要点介绍
常见的精神障碍有抑郁症、焦虑症、饮食障碍、睡眠障碍、双相情感障碍、性行为障碍和孤独症等。根据世界卫生组织(WHO)的数据,大约五分之一的人在一生中都会遇到精神障碍。研究精神障碍的发病机制是治疗精神障碍的关键。
MGB轴为探索精神障碍的发病机制和制定合适的治疗策略提供了一条新的途径。肠道菌群通过肠-脑轴的通讯途径对脑部相关疾病有着重要影响,肠道微生物群可以产生多种神经递质。神经递质是一种化学物质,它影响着宿主的情绪、认知和行为,是调节MGB轴的关键部分。
为了深入研究肠道微生物群和神经递质在精神障碍发展中的作用,我们将现有研究的结果收集到一个结构化的知识库(即知识图谱)中。知识图谱是一个由实体和概念以及它们之间的语义关系组成的大规模语义网络,通过更快地搜索潜在的关系,从而支持做出更好的决策。知识图谱技术已经被应用于许多生物医学的实际问题,如从基于电子病历的知识图谱中学习高质量的知识,以及预测微生物与人类疾病之间的关系等。
在这篇论文中,我们提出了一个新的基于知识图谱的微生物群知识图来揭示肠道微生物群、神经递质和精神障碍之间的潜在关联,我们称之为MiKG。它包括许多连接到众所周知的生物医学本体知识库的接口,例如UMLS、MeSH、KEGG和SNOMED CT,并且可以通过连接到未来的本体库进行扩展,进一步研究肠道微生物群和神经递质之间的关系。
本研究的主要贡献如下:
1. 新的思路:将关于神经递质与肠道微生物关系研究的结果结构化到一个知识库。
2. 新的方法:以结构化的方式表达自由文本中肠道微生物、神经递质与精神疾病之间的语义关系,使之不仅人类可读且机器可读。3. 新的模型:以知识图谱挖掘肠道微生物与神经递质之间潜在关系,辅助未来研究。
图1. MGB轴图示。肠道微生物群通过肠道和大脑之间的双向信号影响宿主的健康状况。双向信号传递途径包括迷走神经、HPA轴、免疫系统、免疫系统产生细胞因子、分泌SCFAs、调节神经递质等。
图2. 构建知识图谱的工作流程。通过文献检索,我们收集了有关肠道微生物群与神经递质、神经递质与精神障碍关系的研究文献。其后提取实体、关系和属性,并将提取的数据结构化为RDF格式,与其他数据库:UMLS、MeSH、SNOMED CT和KEGG一起存储于GraphDB。GraphDB是一个提供SPARQL查询功能的平台。我们将知识图命名为MiKG。
图3. 知识图谱。蓝色和粉色的圆形簇分别代表TBox(术语)和ABox(推断)。箭头的标签标明特定的属性或关系,而箭头则表示属性或关系从源到目标的方向。概念通过CUI/MeSH ID链接到UMLS/MeSH,神经递质通过Map ID和C编号链接到KEGG数据库。
研究结论:为了预测肠道微生物群与精神障碍之间的关系,以神经递质为连接元素,我们首先以语义的方式整合现有生物医学研究中分散的知识,构建了一个知识图谱:MiKG。然后,我们设计了多个SPARQL查询用例以展示此知识图谱的检索和推理功能等。实验结果表明MiKG是揭示肠道微生物群、神经递质和精神障碍之间潜在联系的有力工具。它不仅有效地支持检索确定的关系,如肠道微生物群和神经递质之间的关系,而且能够推断出隐含的关系,如肠道微生物群通过神经递质对心理健康的影响。总之,MiKG是一个识别、检索和预测肠道微生物群、神经递质和精神障碍之间关系的有效工具。它有可能推断出合理的假设,从而加速开发新的治疗精神障碍的方法,并有利于未来对MGB轴的研究。
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原文信息
T. Liu, X. Pan, X. Wang, K. A. Feenstra, J. Heringa, Z. Huang, "Exploring the Microbiota-Gut-Brain Axis for Mental Disorders with Knowledge Graphs", Journal of Artificial Intelligence for Medical Sciences, 2021, DOI: 10.2991/jaims.d.201208.001.
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