Abstract
Cryptosporidium parvum (C. parvum) is a protozoan parasite known for cryptosporidiosis in pre-weaned calves. Animals and patients with immunosuppression are at risk of developing the disease, which can cause potentially fatal diarrhoea. The present study aimed to construct a network biology framework based on the differentially expressed genes (DEGs) of C. parvum infected subjects. In this way, the gene expression profiling analysis of C. parvum infected individuals can give us a snapshot of actively expressed genes and transcripts under infection conditions. In the present study, we have analyzed microarray data sets and compared the gene expression profiles of the patients with the different data sets of the healthy control. Using a network medicine approach to identify the most influential genes in the gene interaction network, we uncovered essential genes and pathways related to C. parvum infection. We identified 164 differentially expressed genes (109 up- and 54 down-regulated DEGs) and allocated them to pathway and gene set enrichment analysis. The results underpin the identification of seven significant hub genes with high centrality values: ISG15, MX1, IFI44L, STAT1, IFIT1, OAS1, IFIT3, RSAD2, IFITM1, and IFI44. These genes are associated with diverse biological processes not limited to host interaction, type 1 interferon production, or response to IL-gamma. Furthermore, four genes (IFI44, IFIT3, IFITM1, and MX1) were also discovered to be involved in innate immunity, inflammation, apoptosis, phosphorylation, cell proliferation, and cell signaling. In conclusion, these results reinforce the development and implementation of tools based on gene profiles to identify and treat Cryptosporidium parvum-related diseases at an early stage.
Highlights
Cryptosporidium species are generally widespread protozoan parasites that cause severe gastrointestinal problems in animals and humans [1]
According to the methodology section’s inclusion and exclusion criteria, microarray gene expression profiles with accession number GSE870476613 were selected containing expression data from intestinal epithelial tissue infected with C. parvum infection (Table S1)
We found 163 differentially expressed genes (DEGs), of which 109 up and 54 down-regulated DEGs from the samples of C. parvum infected tissue, and healthy control sets were compared after applying the statistical threshold of log2 BH-p-value
Summary
Cryptosporidium species are generally widespread protozoan parasites that cause severe gastrointestinal problems in animals and humans [1]. Cryptosporidium parvum infects a variety of domestic and wild animals, in addition to humans, it is known to be an important agent associated with zoonotic cryptosporidiosis [2]. Pre-weaned calves have occasionally been found to host other Cryptosporidium species [3,4]. The Centers for disease Control and Prevention, United States, have classified Cryptosporidium as an emerging protozoan parasite affecting 748,000 humans in the United States every year [5]. The gastrointestinal epithelium acts as an active site of infection in many vertebrate hosts; understanding the host-parasite interaction in Cryptosporidium has significant importance [7,8]
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