title: Identification of putative drug targets for human sperm-egg interaction defect using protein network approach.
abstract: BACKGROUND
  Sperm-egg interaction defect is a significant cause of in-vitro fertilization failure for infertile cases. Numerous molecular interactions in the form of protein-protein interactions mediate the sperm-egg membrane interaction process. Recent studies have demonstrated that in addition to experimental techniques, computational methods, namely protein interaction network approach, can address protein-protein interactions between human sperm and egg. Up to now, no drugs have been detected to treat sperm-egg interaction disorder, and the initial step in drug discovery research is finding out essential proteins or drug targets for a biological process. The main purpose of this study is to identify putative drug targets for human sperm-egg interaction deficiency and consider if the detected essential proteins are targets for any known drugs using protein-protein interaction network and ingenuity pathway analysis.
  
  
  RESULTS
  We have created human sperm-egg protein interaction networks with high confidence, including 106 nodes and 415 interactions. Through topological analysis of the network with calculation of some metrics, such as connectivity and betweenness centrality, we have identified 13 essential proteins as putative drug targets. The potential drug targets are from integrins, fibronectins, epidermal growth factor receptors, collagens and tetraspanins protein families. We evaluated these targets by ingenuity pathway analysis, and the known drugs for the targets have been detected, and the possible effective role of the drugs on sperm-egg interaction defect has been considered. These results showed that the drugs ocriplasmin (Jetrea©), gefitinib (Iressa©), erlotinib hydrochloride (Tarceva©), clingitide, cetuximab (Erbitux©) and panitumumab (Vectibix©) are possible candidates for efficacy testing for the treatment of sperm-egg interaction deficiency. Further experimental validation can be carried out to confirm these results.
  
  
  CONCLUSIONS
  We have identified the first potential list of drug targets for human sperm-egg interaction defect using the protein interaction network approach. The essential proteins or potential drug targets were found using topological analysis of the protein network. These putative targets are promising for further experimental validation. These study results, if validated, may develop drug discovery techniques for sperm-egg interaction defect and also improve assisted reproductive technologies to avoid in-vitro fertilization failure.
authors.affiliation: Department of Biosciences and Health Sciences, Faculty of Bioscience and Medical Engineering, Universiti Teknologi Malaysia, Johor, Malaysia. soudabehsabet@gmail.com.
authors.forename: Soudabeh
authors.initials: S
authors.lastname: Sabetian
authors.affiliation: Department of Biosciences and Health Sciences, Faculty of Bioscience and Medical Engineering, Universiti Teknologi Malaysia, Johor, Malaysia. shahir@fbb.utm.my.
authors.forename: Mohd Shahir
authors.initials: MS
authors.lastname: Shamsir
mesh_terms: D019295:Computational Biology / Q000379:methods*; D004527:Egg Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007246:Infertility / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D058990:Molecular Targeted Therapy; D025941:Protein Interaction Mapping / Q000379:methods*; D013084:Sperm-Ovum Interactions / Q000187:drug effects*
chemical_list: D004527:Egg Proteins