Comparative Analysis of Microarray and Next Generation Sequencing Data of Down’s Syndrome for the Identification of Therapeutic Targets

Abstract

Down’s syndrome is the most common genetic aberration with the frequency of one in 700 live births worldwide. The most alarming situation for the patients with Down’s syndrome is the presence of accompanying neurological, congenital heart, intestinal, neuromuscular and immune system disorders. Supernumerary of chromosome 21(HSA21) is due to the different mechanisms such as chromosome non-disjunction during meiosis II, translocation of chromosome and mosaicism. Age, lifestyle and diet of the mother are the main risk factors which elevate the occurrence of DS in newborn. Since HSA21 sequenced in 2000, scientists explored the relation of other disorders with DS. Although, many disorders caused by trisomy but the exact pathways that lead to these disorders are still unclear. Previously, differentially expressed genes and pathways related to the DS found either by microarray or RNAsequencing data separately or by using just one type of tissue samples. In this research, we looked into the holistic picture of DS by comparative analysis of microarray and RNA-sequencing data of different tissue samples as well as by investigating weighted co-expressed gene modules. For this analysis, 4 microarray datasets and 3 RNAsequencing datasets obtained from publicly available databases. We found CFAP298 (Cilia And Flagella Associated Protein 298) common gene in all datasets. There were 3 common genes in microarray datasets and 37 common genes in RNA-seq datasets found out. There was no common enriched pathway obtained in comparative analysis of individual gene set enrichment analysis of all datasets. Weighted gene co-expression analysis obtained modules of co expressed hub genes in DS. GSEA of selected hub genes resulted into the 25 significant enriched pathways. The most enriched and significant up-regulated pathways contain pathways of staphylococcus aureus infection, DNA replication, cell adhesion molecules, phagosome, cell cycle, oocyte meiosis, progesterone-mediated oocyte maturation, fanconi anemia pathway, bile secretion and cholesterol metabolism. On the other hand herpes simplex virus 1 1 Abstract infection, tight junction, cytokine-cytokine receptor interaction, thyroid cancer pathways and legionellosis are down-regulated pathways.