Systematic Analysis of Protein Interaction Network Associated with Azoospermia.
Non-obstructive azoospermia is a severe infertility factor. Currently, the etiology of this condition remains elusive with several possible molecular pathway disruptions identified in the post-meiotic spermatozoa. In the presented study, in order to identify all possible candidate genes associated with azoospermia and to map their relationship, we present the first protein-protein interaction network related to azoospermia and analyze the complex effects of the related genes systematically. Using Online Mendelian Inheritance in Man, the Human Protein Reference Database and Cytoscape, we created a novel network consisting of 209 protein nodes and 737 interactions. Mathematical analysis identified three proteins, ar, dazap2, and esr1, as hub nodes and a bottleneck protein within the network. We also identified new candidate genes,CREBBPandBCAR1, which may play a role in azoospermia. The gene ontology analysis suggests a genetic link between azoospermia and liver disease. The KEGG analysis also showed 45 statistically important pathways with 31 proteins associated with colorectal, pancreatic, chronic myeloid leukemia and prostate cancer. Two new genes and associated diseases are promising for further experimental validation.
Department of Biological and Health Sciences, Faculty of Bioscience & Medical Engineering, Universiti Teknologi Malaysia, 81310 Johor, Malaysia. soudabehsabet@gmail.com.
Soudabeh
S
Sabetian
Department of Biological and Health Sciences, Faculty of Bioscience & Medical Engineering, Universiti Teknologi Malaysia, 81310 Johor, Malaysia. shahir@utm.my.
Mohd Shahir
MS
Shamsir
D000465:Algorithms; D053713:Azoospermia / Q000235:genetics* / Q000378:metabolism; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D050719:Crk-Associated Substrate Protein / Q000235:genetics / Q000378:metabolism; D030541:Databases, Genetic; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008957:Models, Genetic; D025941:Protein Interaction Mapping / Q000379:methods; D060066:Protein Interaction Maps / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism
C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; C498224:DAZAP2 protein, human; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen; D050882:CREB-Binding Protein; C494363:CREBBP protein, human
azoospermia; gene ontology; infertility; protein interaction network