IDENTIFICATION OF KEY TARGET GENES AND
PATHWAY ANALYSIS IN NONALCOHOLIC FATTY LIVER
DISEASE VIA INTEGRATED BIOINFORMATICS ANALYSIS
Chen X.1, Zhang L.2, Wang Y.1, Li R.1, Yang M.1, Gao L.3*
*Corresponding Author: Lei Gao, MD, College of Basic Medicine, Changchun University of Chinese
Medicine, 1035 Boshuo, Road, Jingyue District, Changchun City, Jilin Province, 130117, China;
Tel:+ 86-431-8604 5309, Email: gaolei790708@163.com
page: 10
|
|
RESULTS
Data preprocessing and DERs screening
A total of 9698 mRNAs and 1116 lncRNAs were detected
after data preprocessing, and a total of 561 DERs
(48 lncRNA and 513 mRNA; 268 downregulated and 293
upregulated) were screened in the baseline time point
group, and 1163 DERs (114 lncRNA and 1049 mRNA;
522 downregulated and 641 upregulated) were screened
in the 1-year follow-up time point group, with FDR < 0.05
and |log2FC| > 0.5 as the cutoff criteria. We identified all
DERs shown in the volcano map according to the value of
|log2FC| and displayed DERs on a heat map (Figure 1A, B).
The expression values of the DERs were 2-way hierarchically
clustered, and the color contrast indicated that there
was a significant difference in expression levels between
the NAFLD and non-NAFLD samples (Figure1 C, D).
Subsequently, a total of 220 overlapping DERs were identified
between the baseline and 1-year follow-up time points,
which were used by the Venn diagram software (Figure 2).
In addition, the functional enrichment analysis of
the overlapping DERs based on online DAVID analyses
revealed 22 significantly related GO biological processes
and 9 KEGG pathways, with P < .05 as the cutoff criteria
(Table 1). We found that chemotaxis (GO, 0006935; P =
3.110E-04), unsaturated fatty acid biosynthetic process
(GO, 0006636; P = 4.770E-04), and cell-cell signaling
(GO, 0007267; P = 1.513E-03) were the three most significant
pathways in GO biological processes. Meanwhile,
fatty acid metabolism (hsa01212, P = 2.300E-04), PPAR
signaling pathway (hsa03320, P = 1.090E-03), and Tolllike
receptor signaling pathway (hsa04620, P = 1.479E-
03) were the three most significant pathways in KEGG
signaling pathways.
Construction of ceRNA regulation network
A total of 77 miRNAs directly related to NAFLD
were downloaded from the HMDD database. After the
lncRNA and miRNA connection relationship pairs were
downloaded and the regulation relationship between significantly
DElncRNA and NAFLD-related DEmiRNAs were
selected, a total of 74 connection pairs were retained to
construct an lncRNA–miRNA connection network with a
connection coefficient higher than 0.6. In addition, after the
target genes of the miRNA were screened, we compared
the regulated target genes with the significant DEmRNAs
in target modules and retained the opposite relationship
pairs of the expressions of significant differential direction.
The miRNA–mRNA regulation network was constructed
by using a total of 523 pairs of regulation relationships.
Finally, as shown Figure 3, a ceRNA regulation network
was constructed.
A total of 28 GO biological processes and 9 KEGG
pathways of the mRNAs in the ceRNA regulatory network
were obtained, with P < .05 as the significance threshold
(Table 2). We found that a lipid biosynthetic process (GO,
0008610; P = 1.15E-06), a steroid metabolic process (GO,
0008202; P = 1.26E-05), and a steroid biosynthetic process
(GO, 0006694; P = 9.34E-05) were the three most significant
pathways in GO biological processes. Meanwhile,
the biosynthesis of unsaturated fatty acids (hsa01040, P =
2.39E-05), terpenoid backbone biosynthesis (hsa00900, P
= 1.090E-03), and heparan sulfate biosynthesis (hsa00534,
P = 1.38E-02) were the three most significant pathways in
KEGG signaling pathways.
Construction of drug regulation gene network
The gene-related drug molecule connection pairs
were downloaded from the PharmGKB database. A total of 154 connection pairs were obtained by selecting the parts
related to the genes in the ceRNA regulatory network, and
a gene–drug connection network was constructed (Figure
4). Compared with the pathway in which the RNAs significantly
participated in the ceRNA regulatory network
constructed in the previous step, the leptin receptor (LEPR)
and CXCL10 are involved in the Cytokine–cytokine receptor
interaction (P = 1.86E-02), and FOXO1 is involved in
both the Insulin signaling pathway (P = 1.79E-02) and the
pathways in cancer (P = 2.87E-02).
|
|
|
|
 |
Number 25
VOL. 25(2), 2022 |
Number 25
VOL. 25 (1), 2022 |
Number 24
VOL. 24(2), 2021 |
Number 24
VOL. 24(1), 2021 |
Number 23
VOL. 23(2), 2020 |
Number 22
VOL. 22(2), 2019 |
Number 22
VOL. 22(1), 2019 |
Number 22
VOL. 22, 2019 Supplement |
Number 21
VOL. 21(2), 2018 |
Number 21
VOL. 21 (1), 2018 |
Number 21
VOL. 21, 2018 Supplement |
Number 20
VOL. 20 (2), 2017 |
Number 20
VOL. 20 (1), 2017 |
Number 19
VOL. 19 (2), 2016 |
Number 19
VOL. 19 (1), 2016 |
Number 18
VOL. 18 (2), 2015 |
Number 18
VOL. 18 (1), 2015 |
Number 17
VOL. 17 (2), 2014 |
Number 17
VOL. 17 (1), 2014 |
Number 16
VOL. 16 (2), 2013 |
Number 16
VOL. 16 (1), 2013 |
Number 15
VOL. 15 (2), 2012 |
Number 15
VOL. 15, 2012 Supplement |
Number 15
Vol. 15 (1), 2012 |
Number 14
14 - Vol. 14 (2), 2011 |
Number 14
The 9th Balkan Congress of Medical Genetics |
Number 14
14 - Vol. 14 (1), 2011 |
Number 13
Vol. 13 (2), 2010 |
Number 13
Vol.13 (1), 2010 |
Number 12
Vol.12 (2), 2009 |
Number 12
Vol.12 (1), 2009 |
Number 11
Vol.11 (2),2008 |
Number 11
Vol.11 (1),2008 |
Number 10
Vol.10 (2), 2007 |
Number 10
10 (1),2007 |
Number 9
1&2, 2006 |
Number 9
3&4, 2006 |
Number 8
1&2, 2005 |
Number 8
3&4, 2004 |
Number 7
1&2, 2004 |
Number 6
3&4, 2003 |
Number 6
1&2, 2003 |
Number 5
3&4, 2002 |
Number 5
1&2, 2002 |
Number 4
Vol.3 (4), 2000 |
Number 4
Vol.2 (4), 1999 |
Number 4
Vol.1 (4), 1998 |
Number 4
3&4, 2001 |
Number 4
1&2, 2001 |
Number 3
Vol.3 (3), 2000 |
Number 3
Vol.2 (3), 1999 |
Number 3
Vol.1 (3), 1998 |
Number 2
Vol.3(2), 2000 |
Number 2
Vol.1 (2), 1998 |
Number 2
Vol.2 (2), 1999 |
Number 1
Vol.3 (1), 2000 |
Number 1
Vol.2 (1), 1999 |
Number 1
Vol.1 (1), 1998 |
|
|
