Document Type
Article
Publication Date
4-29-2021
Publication Title
Genes
Volume
12
Issue
5
First page number:
1
Last page number:
15
Abstract
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 intercoordination 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 (PAK1:SYT1, PAK1:RFC5, DCTN1:STX1A, and GRIA1:MAP2K4) 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.
Keywords
Differential co-expression; Pathway crosstalk; PSMC6; Schizophrenia
Disciplines
Genetics and Genomics
File Format
File Size
1473 KB
Language
English
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Repository Citation
Yu, H.,
Guo, Y.,
Chen, J.,
Chen, X.,
Jia, P.,
Zhao, Z.
(2021).
Rewired Pathways and Disrupted Pathway Crosstalk in Schizophrenia Transcriptomes by Multiple Differential Coexpression Methods.
Genes, 12(5),
1-15.
http://dx.doi.org/10.3390/genes12050665