Identification of Novel Therapeutic Targets in Myelodysplastic Syndrome Using Protein-Protein Interaction Approach and Neural Networks

Abstract

A Myelodysplastic syndrome (MDS) is a disorder characterized by active but ineffective hematopoiesis that leads to pancytopenia. MDS, also termed as myeloid neoplasms, is described by different level of cytopenia that is a different level of blood cells in the body. Various genes mutations have been reported to associate with MDS. To investigate the mechanisms at molecular level underlying MDS patients carrying genetic mutations, the gene expression profiles of MDS the patients were compared to that of healthy individuals and analyzed by bioinformatics tools. In biological networks, genes having important functional roles can be identified by a measure of the node. Networks of genes an in co-expression, candidate hubs also called extremely associated genes have been connected with the key disease-related pathway. Thus, this technique was used to discover the MDS related genes hub. Affymetrix Human Genome U133 plus 2.0 gene expression dataset of microarray GSE58831 was retrieved from GEO (Gene Expression Omnibus) database that contained four 159 diseased samples and 17 samples of control. Based on statistical method and co-expression networking, DEGs gene was detected. DAVID an online tool was employed for Gene ontology (GO) function and KEGG pathway enrichment analysis of DEGs. Besides, PPI (Protein-protein interaction) networks were developed by mapping the DEGs with respect to protein-protein interaction set available in databases for the identification of the pathways involving DEGs. PPI interaction networks were divided into subnetworks via MCODE algorithm and were examined by Cytoscape. Interferon Signaling Pathway, cellular response to zinc ions and negative growth regulation. Immune response, negative regulation of transcription from RNA polymerase II promotor, positive regulation of smooth muscle cell proliferation and cellular response to Dexamethasone stimulus, extracellular matrix, extracellular space, and extracellular region were the main enriched processes and pathways in these DEGs and many of the hub genes’ (UBC, TP53, EGFR, GADPH, CREBBP, HDAC1, STAT1, IL6, ESR1, SMAD4) reported in this study were purposed as novel therapeutic targets against MDS disease.