Rewired Pathways and Disrupted Pathway Crosstalk in Schizophrenia Transcriptomes by Multiple Differential Coexpression Methods
Transcriptomic studies of mental disorders using the human brain tissues have been limited, and gene expression signatures in schizophrenia (SCZ) remain elusive. In this study, we applied three differential co-expression methods to analyze five transcriptomic datasets (three RNA-Seq and two microarr...
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doaj-f1b2a4587c924dd1ba1b635486797ade2021-04-29T23:00:29ZengMDPI AGGenes2073-44252021-04-011266566510.3390/genes12050665Rewired Pathways and Disrupted Pathway Crosstalk in Schizophrenia Transcriptomes by Multiple Differential Coexpression MethodsHui Yu0Yan Guo1Jingchun Chen2Xiangning Chen3Peilin Jia4Zhongming Zhao5Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USADepartment of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USANevada Institute of Personalized Medicine, University of Nevada Las Vegas, Las Vegas, NV 89154, USANevada Institute of Personalized Medicine, University of Nevada Las Vegas, Las Vegas, NV 89154, USACenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USACenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USATranscriptomic studies of mental disorders using the human brain tissues have been limited, and gene expression signatures in schizophrenia (SCZ) remain elusive. In this study, we applied three differential co-expression methods to analyze five transcriptomic datasets (three RNA-Seq and two microarray datasets) derived from SCZ and matched normal postmortem brain samples. We aimed to uncover biological pathways where internal correlation structure was rewired or inter-coordination was disrupted in SCZ. In total, we identified 60 rewired pathways, many of which were related to neurotransmitter, synapse, immune, and cell adhesion. We found the hub genes, which were on the center of rewired pathways, were highly mutually consistent among the five datasets. The combinatory list of 92 hub genes was generally multi-functional, suggesting their complex and dynamic roles in SCZ pathophysiology. In our constructed pathway crosstalk network, we found “Clostridium neurotoxicity” and “signaling events mediated by focal adhesion kinase” had the highest interactions. We further identified disconnected gene links underlying the disrupted pathway crosstalk. Among them, four gene pairs (<i>PAK1:SYT1</i>, <i>PAK1:RFC5</i>, <i>DCTN1:STX1A</i>, and <i>GRIA1:MAP2K4</i>) were normally correlated in universal contexts. In summary, we systematically identified rewired pathways, disrupted pathway crosstalk circuits, and critical genes and gene links in schizophrenia transcriptomes.https://www.mdpi.com/2073-4425/12/5/665differential co-expressionpathway crosstalkschizophreniaPSMC6 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hui Yu Yan Guo Jingchun Chen Xiangning Chen Peilin Jia Zhongming Zhao |
spellingShingle |
Hui Yu Yan Guo Jingchun Chen Xiangning Chen Peilin Jia Zhongming Zhao Rewired Pathways and Disrupted Pathway Crosstalk in Schizophrenia Transcriptomes by Multiple Differential Coexpression Methods Genes differential co-expression pathway crosstalk schizophrenia PSMC6 |
author_facet |
Hui Yu Yan Guo Jingchun Chen Xiangning Chen Peilin Jia Zhongming Zhao |
author_sort |
Hui Yu |
title |
Rewired Pathways and Disrupted Pathway Crosstalk in Schizophrenia Transcriptomes by Multiple Differential Coexpression Methods |
title_short |
Rewired Pathways and Disrupted Pathway Crosstalk in Schizophrenia Transcriptomes by Multiple Differential Coexpression Methods |
title_full |
Rewired Pathways and Disrupted Pathway Crosstalk in Schizophrenia Transcriptomes by Multiple Differential Coexpression Methods |
title_fullStr |
Rewired Pathways and Disrupted Pathway Crosstalk in Schizophrenia Transcriptomes by Multiple Differential Coexpression Methods |
title_full_unstemmed |
Rewired Pathways and Disrupted Pathway Crosstalk in Schizophrenia Transcriptomes by Multiple Differential Coexpression Methods |
title_sort |
rewired pathways and disrupted pathway crosstalk in schizophrenia transcriptomes by multiple differential coexpression methods |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2021-04-01 |
description |
Transcriptomic studies of mental disorders using the human brain tissues have been limited, and gene expression signatures in schizophrenia (SCZ) remain elusive. In this study, we applied three differential co-expression methods to analyze five transcriptomic datasets (three RNA-Seq and two microarray datasets) derived from SCZ and matched normal postmortem brain samples. We aimed to uncover biological pathways where internal correlation structure was rewired or inter-coordination was disrupted in SCZ. In total, we identified 60 rewired pathways, many of which were related to neurotransmitter, synapse, immune, and cell adhesion. We found the hub genes, which were on the center of rewired pathways, were highly mutually consistent among the five datasets. The combinatory list of 92 hub genes was generally multi-functional, suggesting their complex and dynamic roles in SCZ pathophysiology. In our constructed pathway crosstalk network, we found “Clostridium neurotoxicity” and “signaling events mediated by focal adhesion kinase” had the highest interactions. We further identified disconnected gene links underlying the disrupted pathway crosstalk. Among them, four gene pairs (<i>PAK1:SYT1</i>, <i>PAK1:RFC5</i>, <i>DCTN1:STX1A</i>, and <i>GRIA1:MAP2K4</i>) were normally correlated in universal contexts. In summary, we systematically identified rewired pathways, disrupted pathway crosstalk circuits, and critical genes and gene links in schizophrenia transcriptomes. |
topic |
differential co-expression pathway crosstalk schizophrenia PSMC6 |
url |
https://www.mdpi.com/2073-4425/12/5/665 |
work_keys_str_mv |
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