In five GEO series. Red represented higher expression of DEGs in asthma patients, when blue represented low expression of DEGs in asthma individuals. The numbers in the box indicated logarithmic fold changes in every dataset; (C) The circular heatmaps showed the chromosomal positions of all robust DEGs. The outer circle represented chromosomes, whilst the inner circle heatmaps represented logarithmic fold changes of all robust DEGs in five asthma microarray datasets.inhibitor activity, and cysteine-type endoCDK5 site peptidase inhibitor activity accounted for the majority on the molecular function terms (Figure 4A). In terms of 44 downregulated genes, the significantly enriched biological course of action terms have been humoralimmune response, response to drug, and pattern specification procedure. Inside the cellular element part, the downregulated genes have been particularly enriched in tight junction, brush border membrane, and Z disc. Meanwhile, endopeptidase andFrontiers in Molecular Biosciences | www.frontiersin.orgJuly 2021 | Volume eight | ArticleChen et al.A ceRNA Fas manufacturer Network in AsthmaFIGURE four | Bar plots and bubble charts of functional annotations involved in asthma. GO enrichment annotations of upregulated DEGs (A) and downregulated DEGs (B) in three categories: BP, CC, and MF; (C) KEGG pathway enrichment analysis of all DEGs; (D) Enrichment analysis of all DEGs in DisGeNET database. GO, Gene Ontology; BP, biological process; CC, cellular component; MF, molecular function; KEGG, the Kyoto Encyclopedia of Genes and Genomes.peptidase regulator activities, enzyme inhibitor activity, and heme binding had been mostly enriched in the molecular function group (Figure 4B). Moreover, integrated DEGs have been mostly involved in salivary secretion, metabolism of xenobiotics by cytochrome P450, IL-17 signaling pathway, and leukocyte transendothelial migration in KEGG pathway evaluation (Figure 4C). The DisGeNET database was further utilized to recognize DEGs connected ailments. As shown in Figure 4D, the result indicated that robust DEGs participated in the progression of a variety of ailments, like Nasal Polyps, Allergic rhinitis disorder, Allergic asthma, and Atopic Dermatitis, which had been all related to allergic reactions and chronic inflammation (Figure 4D). Taken collectively, the above final results indicated that the robust DEGs were mainly related with asthma-related functions.Protein-Protein Interaction Network Construction, Clusters Evaluation, and Hub Gene IdentificationIn order to explore the potential protein-protein interactions in asthma, all 127 robust DEGs were uploaded for the STRING database for further analysis (http://string.embl.de/). Right after hiding the disconnected nodes, the Cytoscape software program was adopted to visualize the network (Figure 5A). As shown within the final network, 77 nodes and 114 edges had been obtained, like 57 upregulated and 20 downregulated genes. Three essential clusters have been identified from the entire network working with the MCODE plugin (Figures 5B ). GO enrichment analyses showed that the considerably enriched biological method terms of 3 clusters have been regulationof myeloid leukocyte mediated immunity, T cell activation, and antibacterial humoral response, respectively (Figure 5E). Hub genes were subsequently screened out using the cytoHubba plugin, which investigates probably the most important nodes within the PPI network with quite a few topological evaluation algorithms. In an effort to improve the good rate of hub gene identification, the RRA technique was applied to integrate the leading 50 rank.