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Gene & Protein in Disease Bioinformatics to identify gene signatures of CF

and basal transcription factors (Figure 4A). The primary GO terms “protein binding” and “cytoplasm.” In addition,
pathways associated with the downregulated DEGs include the cytoHubba program enabled us to identify the top 6
proteolysis mediated by ubiquitin, nucleotide excision hub genes (CDC42, UBA2, HDAC4, CUL1, RNASEL, and
repair, and cell cycle (Figure 4B). Tables S3-S5 provide the WWP2) from the PPI network (Figure 7). Table 2 displays the
outputs of GO and KEGG analysis of the DEGs. topological metrics for each of the five molecular hub genes
in the PPI linkage, including each gene’s degree, betweenness
3.3. PPI network construction centrality, clustering coefficient, and closeness centrality.
With the STRING, we were able to determine the PPI
networks for both up and downregulated genes, which 5. Discussion
allowed us to assess the PPIs linked to the DEGs. For CF is a recessive inherited disorder that causes death in 90%
visualization, we loaded the generated PPI network as a of patients. The major dysfunctions of CF include mucus-
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“.csv” file and entered Cytoscape v3.8.0 after exporting it as blocked airways leading to severe lung infections, massive
a “.txt” file from STRING. For both up and downregulated neutrophil infiltration, and inflammation contributing to
DEGs, we separately enhanced the PPI networks. Once tissue damage. Although the vast majority of morbidity
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all 211 DEGs had been found, we combined the PPI and mortality is accounted for by chronic progressive lung
networks. As shown in Figure 5B and C, the PPI networks disease in CF, it is important to note that CF is not confined
for up- and down-regulated DEGs include 74 nodes and to the lungs and may affect other major organs resulting
191 connections, and 82 nodes and 282 connections, in several comorbidities. However, current treatment
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respectively. There were 515 edges overall for 167 nodes in approaches are not effective in all patients. For instance,
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the combined PPI network including all DEGs (Figure 5A). highly effective modulator therapy is not efficacious to
4.4. Identification of gene signatures: Module 10 – 20% of CF patients, and the multidrug bacterial
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analysis from PPI network resistance also limits the current antimicrobial choices.
On the other hand, it has recently been reported that many
Using the Cytoscape plugin MCODE, we were able to children with CF are born without any clinical symptoms,
identify two important modules from the combined and the diagnosis was only confirmed their birth. Thus,
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PPI network. Figure 6A shows that Module 1 exhibited the search for early and precise detection of CF has become
13 nodes and 55 connections, while eight nodes and 12 more intense in recent years, especially for techniques to
connections occurred in Module 2 (Figure 6B). The DEGs identify gene signatures. In the present study, we evaluated
of the modules had a vital impact in enriching critical
the DEGs, gene networks, pathways, and protein–protein
A connections that are exclusive to CF. We used temperature
as a means to manipulate gene expression from the GSE
dataset. It has been reported that cell growth was nearly
halted after moderate hypothermia and did not resume
when temperatures returned to 37°C. The expression of cold
shock genes, CIRBP and RBM3, was enhanced at 25°C and
recovered to baseline levels following rewarming, whereas
that of HSP70 was inversely regulated. Our data also
supported that the temperature can affect gene expression,
B a finding consistent with another published study. 45

The volcano plot (Figure 2) in this article was used to
visualize the patterns of the DEGs from both the control
and treated groups. Upregulated genes are denoted by
green points, while downregulated genes are represented
by red points.
Following the enrichment, we identified a few important
GO terms enriched in the upregulated genes, including:
protein kinase activity, N-acyl phosphatidylethanolamine-
specific phospholipase D activity, N,N-dimethylaniline
Figure 4. Identification of Kyoto Encyclopedia of Genes and Genomes monooxygenase activity, transcription, and protein
(KEGG) pathways following enrichment with differentially expressed
genes. (A) KEGG pathways enriched in upregulated genes. (B) KEGG phosphorylation in the biological process; nucleoplasm,
pathways enriched in downregulated genes. cytoplasm, and zinc ion binding in the cellular component; and

Volume 3 Issue 2 (2024) 5 doi: 10.36922/gpd.2937