RT Journal Article
SR Electronic
T1 Systematic search for schizophrenia pathways sensitive to perturbation by immune activation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 730655
DO 10.1101/730655
A1 Yue Gao
A1 Xiaozhen Liang
A1 Zhonglu Ren
A1 Yanjun Li
A1 Xinping Yang
YR 2019
UL http://biorxiv.org/content/early/2019/08/12/730655.abstract
AB Immune activation has been recently found to play a large part in the development of schizophrenia, but the underlying mechanism remains largely unknown. Here, we report the construction of a high-quality protein interaction network for schizophrenia (SCZ Network) using a “neighborhood walking” approach to searching across human interactome network for disease-related neighborhoods. The spatiotemporal expression pattern of the immune genes in the SCZ Network demonstrates that this disease network is sensitive to the perturbation of immune activation during mid- to late fetal development and adolescence. The immune genes in the network are involved in pathways regulating the formation, structure and function of synapses and neural connections. Using single-cell transcriptome sequencing on the brains of immune-activated mice, we found that immune activation disturbed the SCZ network in the major brain cell types and the dysregulated pathways were also involved in synapse regulation, demonstrating that our “neighborhood walking” approach enables biological discovery in complex disorders.