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2018 ; 11
(1
): 40
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A meta-analysis of public microarray data identifies biological regulatory
networks in Parkinson s disease
#MMPMID29653596
Su L
; Wang C
; Zheng C
; Wei H
; Song X
BMC Med Genomics
2018[Apr]; 11
(1
): 40
PMID29653596
show ga
BACKGROUND: Parkinson's disease (PD) is a long-term degenerative disease that is
caused by environmental and genetic factors. The networks of genes and their
regulators that control the progression and development of PD require further
elucidation. METHODS: We examine common differentially expressed genes (DEGs)
from several PD blood and substantia nigra (SN) microarray datasets by
meta-analysis. Further we screen the PD-specific genes from common DEGs using
GCBI. Next, we used a series of bioinformatics software to analyze the miRNAs,
lncRNAs and SNPs associated with the common PD-specific genes, and then identify
the mTF-miRNA-gene-gTF network. RESULT: Our results identified 36 common DEGs in
PD blood studies and 17 common DEGs in PD SN studies, and five of the genes were
previously known to be associated with PD. Further study of the regulatory miRNAs
associated with the common PD-specific genes revealed 14 PD-specific miRNAs in
our study. Analysis of the mTF-miRNA-gene-gTF network about PD-specific genes
revealed two feed-forward loops: one involving the SPRK2 gene, hsa-miR-19a-3p and
SPI1, and the second involving the SPRK2 gene, hsa-miR-17-3p and SPI. The long
non-coding RNA (lncRNA)-mediated regulatory network identified lncRNAs associated
with PD-specific genes and PD-specific miRNAs. Moreover, single nucleotide
polymorphism (SNP) analysis of the PD-specific genes identified two significant
SNPs, and SNP analysis of the neurodegenerative disease-specific genes identified
seven significant SNPs. Most of these SNPs are present in the 3'-untranslated
region of genes and are controlled by several miRNAs. CONCLUSION: Our study
identified a total of 53 common DEGs in PD patients compared with healthy
controls in blood and brain datasets and five of these genes were previously
linked with PD. Regulatory network analysis identified PD-specific miRNAs,
associated long non-coding RNA and feed-forward loops, which contribute to our
understanding of the mechanisms underlying PD. The SNPs identified in our study
can determine whether a genetic variant is associated with PD. Overall, these
findings will help guide our study of the complex molecular mechanism of PD.