Genes associated with situs inversus in patients with primary ciliary dyskinesia are identified by the weighted gene correlation network analysis

Background: Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder characterized by immotile and dysmotile cilia or absence of cilia. Situs inversus (SI) is one of the phenomena frequently observed in PCD. However, little is known about the association between SI with PCD. Material and Methods. The microarray data of PCD were retrieved from the Gene Expression Omnibus (GEO) database to construct the co-expression network by the weighted gene co-expression network analysis (WGCNA). R software package Limma was used to perform the differential analysis. The gene network modules associated with SI screened with the common genes were further annotated based on Gene Ontology (GO) database and enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Gene Set Enrichment Analysis (GSEA) was applied to identify the significant pathways. CIBERSORT was used to perform the correlation analysis of immune cells. The protein-protein interaction (PPI) network was constructed based on STRING database to identify the hub genes in the network. Results. Genes involved in PCD were identified related to SI. The results of the correlation analysis of immune cells showed that there were significant differences in the activated contents of dendritic cells. The WGCNA analysis revealed a total of 8 hub genes (i.e., ATP5A1, NDUFS3, NDUFV2, PSMC3, UBE2M, ALDH18A1, DBT, FOXRED1 ). Based on the GO annotations of hub genes, a group of GO terms were revealed to show significant difference, including mitochondrial part, oxidoreductase complex, cytosol, mitochondrial respiratory chain complex I, NADH dehydrogenase complex, respiratory chain complex I, catalytic complex, mitochondrial envelope, respiratory chain complex, and mitochondrial respiratory chain. KEGG enrichment analysis of hub genes identified a group of metabolic pathways showing significant difference, including Propanoate metabolism, beta-Alanine metabolism, Fatty acid degradation, Valine, leucine and isoleucine degradation, Huntington disease, Carbon metabolism, Fatty acid metabolism, Lysine degradation, Butanoate metabolism, and Metabolic pathways. Conclusion. Our study identified the variations in immune cells in PCD patients. The hub genes provide novel therapeutic targets for the diagnosis and treatment of PCD and SI.