Systematic discovery of signaling pathways linking immune activation to schizophrenia

Summary: Immune activation has been shown to play a critical role in the development of schizophrenia; however its underlying mechanism remains unknown. Our report demonstrates a high-quality protein interaction network for schizophrenia (SCZ Network), constructed using our “neighborhood walk” appro...

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Autores principales:	Yue Gao, Yanjun Li, ShuangYan Li, Xiaozhen Liang, Zhonglu Ren, Xiaoxue Yang, Bin Zhang, Yanhui Hu, Xinping Yang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Clinical neuroscience Immunology Bioinformatics Biocomputational method Systems biology Science Q
Acceso en línea:	https://doaj.org/article/c6561cd8773848d7b415e33ca869cbe8
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spelling	oai:doaj.org-article:c6561cd8773848d7b415e33ca869cbe82021-11-20T05:08:19ZSystematic discovery of signaling pathways linking immune activation to schizophrenia2589-004210.1016/j.isci.2021.103209https://doaj.org/article/c6561cd8773848d7b415e33ca869cbe82021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221011779https://doaj.org/toc/2589-0042Summary: Immune activation has been shown to play a critical role in the development of schizophrenia; however its underlying mechanism remains unknown. Our report demonstrates a high-quality protein interaction network for schizophrenia (SCZ Network), constructed using our “neighborhood walk” approach in combination with “random walk with restart”. The spatiotemporal expression pattern of the genes in this disease network revealed two developmental stages sensitive to perturbation by immune activation: mid-to late gestation, and adolescence. Furthermore, we induced immune activation at these stages in mice, carried out transcriptome sequencing on the mouse brains, and illustrated clear potential molecular pathways and key regulators correlating maternal immune activation during gestation and an increased risk for schizophrenia after a second immune activation at puberty. This work provides not only valuable resources for the study on molecular mechanisms underlying schizophrenia, but also a systematic strategy for the discovery of molecular pathways of complex mental disorders.Yue GaoYanjun LiShuangYan LiXiaozhen LiangZhonglu RenXiaoxue YangBin ZhangYanhui HuXinping YangElsevierarticleClinical neuroscienceImmunologyBioinformaticsBiocomputational methodSystems biologyScienceQENiScience, Vol 24, Iss 11, Pp 103209- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Clinical neuroscience Immunology Bioinformatics Biocomputational method Systems biology Science Q
spellingShingle	Clinical neuroscience Immunology Bioinformatics Biocomputational method Systems biology Science Q Yue Gao Yanjun Li ShuangYan Li Xiaozhen Liang Zhonglu Ren Xiaoxue Yang Bin Zhang Yanhui Hu Xinping Yang Systematic discovery of signaling pathways linking immune activation to schizophrenia
description	Summary: Immune activation has been shown to play a critical role in the development of schizophrenia; however its underlying mechanism remains unknown. Our report demonstrates a high-quality protein interaction network for schizophrenia (SCZ Network), constructed using our “neighborhood walk” approach in combination with “random walk with restart”. The spatiotemporal expression pattern of the genes in this disease network revealed two developmental stages sensitive to perturbation by immune activation: mid-to late gestation, and adolescence. Furthermore, we induced immune activation at these stages in mice, carried out transcriptome sequencing on the mouse brains, and illustrated clear potential molecular pathways and key regulators correlating maternal immune activation during gestation and an increased risk for schizophrenia after a second immune activation at puberty. This work provides not only valuable resources for the study on molecular mechanisms underlying schizophrenia, but also a systematic strategy for the discovery of molecular pathways of complex mental disorders.
format	article
author	Yue Gao Yanjun Li ShuangYan Li Xiaozhen Liang Zhonglu Ren Xiaoxue Yang Bin Zhang Yanhui Hu Xinping Yang
author_facet	Yue Gao Yanjun Li ShuangYan Li Xiaozhen Liang Zhonglu Ren Xiaoxue Yang Bin Zhang Yanhui Hu Xinping Yang
author_sort	Yue Gao
title	Systematic discovery of signaling pathways linking immune activation to schizophrenia
title_short	Systematic discovery of signaling pathways linking immune activation to schizophrenia
title_full	Systematic discovery of signaling pathways linking immune activation to schizophrenia
title_fullStr	Systematic discovery of signaling pathways linking immune activation to schizophrenia
title_full_unstemmed	Systematic discovery of signaling pathways linking immune activation to schizophrenia
title_sort	systematic discovery of signaling pathways linking immune activation to schizophrenia
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/c6561cd8773848d7b415e33ca869cbe8
work_keys_str_mv	AT yuegao systematicdiscoveryofsignalingpathwayslinkingimmuneactivationtoschizophrenia AT yanjunli systematicdiscoveryofsignalingpathwayslinkingimmuneactivationtoschizophrenia AT shuangyanli systematicdiscoveryofsignalingpathwayslinkingimmuneactivationtoschizophrenia AT xiaozhenliang systematicdiscoveryofsignalingpathwayslinkingimmuneactivationtoschizophrenia AT zhongluren systematicdiscoveryofsignalingpathwayslinkingimmuneactivationtoschizophrenia AT xiaoxueyang systematicdiscoveryofsignalingpathwayslinkingimmuneactivationtoschizophrenia AT binzhang systematicdiscoveryofsignalingpathwayslinkingimmuneactivationtoschizophrenia AT yanhuihu systematicdiscoveryofsignalingpathwayslinkingimmuneactivationtoschizophrenia AT xinpingyang systematicdiscoveryofsignalingpathwayslinkingimmuneactivationtoschizophrenia
_version_	1718419565983039488

Systematic discovery of signaling pathways linking immune activation to schizophrenia

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