Identification of differentially expressed genes and signaling pathways with Candida infection by bioinformatics analysis

Abstract

Background: Opportunistic Candida species causes severe infections when the human immune system is weakened, leading to high mortality.

Methods: In our study, bioinformatics analysis was used to study the high-throughput sequencing data of samples infected with four kinds of Candida species. And the hub genes were obtained by statistical analysis.

Results: A total of 547, 422, 415 and 405 differentially expressed genes (DEGs) of Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis groups were obtained, respectively. A total of 216 DEGs were obtained after taking intersections of DEGs from the four groups. A protein-protein interaction (PPI) network was established using these 216 genes. The top 10 hub genes (FOSB, EGR1, JUNB, ATF3, EGR2, NR4A1, NR4A2, DUSP1, BTG2, and EGR3) were acquired through calculation by the cytoHubba plug-in in Cytoscape software. Validated by the sequencing data of peripheral blood, JUNB, ATF3 and EGR2 genes were significant statistical significance.

Conclusions: In conclusion, our study demonstrated the potential pathogenic genes in Candida species and their underlying mechanisms by bioinformatic analysis methods. Further, after statistical validation, JUNB, ATF3 and EGR2 genes were attained, which may be used as potential biomarkers with Candida species infection.

Keywords: Bioinformatics analysis; Candida; Differentially expressed genes; High-throughput sequencing; Signaling pathways.

Fig. 1

Heat map and volcano map of DEGs from four groups of Candida species. AB Candida albicans, CD Candida glabrata, EF Candida parapsilosis, and GH Candida tropicalis. In heat maps, gene expression data are converted into a data matrix. Each column represents the genetic data of a sample, and each row represents a gene. The color of each cell represents the expression level, and there are references to expression levels in different colors in the upper right corner of the figure. In volcano maps, red dots indicated up-regulated genes. The green or blue dots indicated down-regulated genes. Black dots indicated the rest of the genes with no significant expression change. The threshold was set as followed: P < 0.05 and |log2FC|≥ 1. FC: fold change

Fig. 2

The biological processes (BP) of GO analysis from four groups of Candida species. A Candida albicans, B Candida glabrata, C Candida parapsilosis, and D Candida tropicalis

Fig. 3

The cellular components (CC) of GO analysis from four groups of Candida species. A Candida albicans, B Candida glabrata, C Candida parapsilosis, and D Candida tropicalis

Fig. 4

The molecular function (MF) of GO analysis from four groups of Candida species. A Candida albicans, B Candida glabrata, C Candida parapsilosis, and D Candida tropicalis

Fig. 5

The analysis of KEGG pathways from four groups of Candida species.  A Candida albicans, B Candida glabrata, C Candida parapsilosis, and D Candida tropicalis

Fig. 6

The intersection results and relevant analysis of DEGs from four groups of Candida species. A The overlapping results of DEGs of four groups of Candida species. Crossed regions indicate co-expressed DEGs. B The gene-miRNA network of overlapping DEGs based on miRTarBase v8.0 database. C The PPI network of overlapping DEGs. D The top 10 hub genes of PPI network

Fig. 7

Verification of hub genes associated with Candida infection. P-value < 0.05 is considered to be statistically significant