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 26
Number 26 VOL. 26(2), 2023 All in one
Number 26
VOL. 26(2), 2023
Number 26
VOL. 26, 2023 Supplement
Number 26
VOL. 26(1), 2023
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

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006