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2017 ; 18
(1
): 721
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Biological networks in Parkinson s disease: an insight into the epigenetic
mechanisms associated with this disease
#MMPMID28899360
Chatterjee P
; Roy D
; Bhattacharyya M
; Bandyopadhyay S
BMC Genomics
2017[Sep]; 18
(1
): 721
PMID28899360
show ga
BACKGROUND: Parkinson's disease (PD) is the second most prevalent
neurodegenerative disorders in the world. Studying PD from systems biology
perspective involving genes and their regulators might provide deeper insights
into the complex molecular interactions associated with this disease. RESULT: We
have studied gene co-expression network obtained from a PD-specific microarray
data. The co-expression network identified 11 hub genes, of which eight genes are
not previously known to be associated with PD. Further study on the functionality
of these eight novel hub genes revealed that these genes play important roles in
several neurodegenerative diseases. Furthermore, we have studied the
tissue-specific expression and histone modification patterns of the novel hub
genes. Most of these genes possess several histone modification sites those are
already known to be associated with neurodegenerative diseases. Regulatory
network namely mTF-miRNA-gene-gTF involves microRNA Transcription Factor (mTF),
microRNA (miRNA), gene and gene Transcription Factor (gTF). Whereas long
noncoding RNA (lncRNA) mediated regulatory network involves miRNA, gene, mTF and
lncRNA. mTF-miRNA-gene-gTF regulatory network identified a novel feed-forward
loop. lncRNA-mediated regulatory network identified novel lncRNAs of PD and
revealed the two-way regulatory pattern of PD-specific miRNAs where miRNAs can be
regulated by both the TFs and lncRNAs. SNP analysis of the most significant genes
of the co-expression network identified 20 SNPs. These SNPs are present in the 3'
UTR of known PD genes and are controlled by those miRNAs which are also involved
in PD. CONCLUSION: Our study identified eight novel hub genes which can be
considered as possible candidates for future biomarker identification studies for
PD. The two regulatory networks studied in our work provide a detailed overview
of the cellular regulatory mechanisms where the non-coding RNAs namely miRNA and
lncRNA, can act as epigenetic regulators of PD. SNPs identified in our study can
be helpful for identifying PD at an earlier stage. Overall, this study may impart
a better comprehension of the complex molecular interactions associated with PD
from systems biology perspective.