Bioinformatics Analysis Of The Etiology Of Congenital Microtia

Objective:The etiology of congenital microtia is complicated,the study of pathogenic genes is dispersive.With the help of a large number of experimental mouse genes and disease phenotypic data in Mouse Genome Informatics(MGI),this study expected to classify the suspicious genes by bioinformatics methods,construct Protein Protein Interaction(PPI)networks,and further analyze the function of screening nodes to identify the functions and interaction relationships of pathogenic gene,predict the potential pathogenic genes,which provide new methods to explain the pathogenesis of congenital microtia and further to clarify the etiology of congenital microtia.Methods:The pathogenic genes of congenital microtia were searched using the MGI.The results were summarized into the STRING database for GO enrichment analysis and KEGG pathway analysis,and then constructed the PPI network to screen the node genes and further study the PPI network and functional enrichment analysis of node genes.Results:1.68 congenital microtia-related pathogenic genes such as FGF8?EYA1 and HOXA2 were searched by MGI;2.The PPI network contained 65 nodes and 174 edges,the average node degree was 5.35,the clustering coefficient was 0.437 and the PPI enrichment P = 0;3.The key node proteins were screened in PPI networks.The top ten were FGF8,CTNNB1?EGFR?PAX6?BCL2?FGF3?FGF10?WNT5A?MAPK3 and FGFR1;4.GO analysis and KEGG pathway analysis showed that pathogenic genes involved in the ear morphogenesis,ear development,embryonic organ morphogenesis,epithelium development and other biological processes;involved in molecular functions such as sequence-specific DNA binding,regulatory region DNA binding and transcription regulatory region DNA binding,and others;expression products of different gene were in the nucleus,intracellular membrane-bounded organelle and other sub-microscopic cell components;pathogenic genes also involved in cancer pathway,melanoma and other diseases,MAPK signaling pathways,RAS signaling pathways and other signaling pathways;5.Key nodes such as FGF3,WNT5A and common nodes such as HOXA2,SIX1 were chose to analyze their PPI,GO and KEGG pathways respectively,and obtain their corresponding information of biological process and molecular function.Conclusions:By using the bioinformatics tool,the PPI network and detailed GO enrichment and KEGG pathway data were obtained by searching the pathogenic genes of congenital microtia in MGI.The key nodes in the study included definite etiology of congenital microtia,such as FGF,BMP,WNT signaling pathways related signal molecules and receptors,which confirmed the feasibility of using bioinformatics methods in this research.It has been shown that the feasibility of using bioinformatics in this study.Studies about PRKRA,FOXI3 and other node genes are few,but they are closely linked with FGF,WNT and other key nodes.By analyzing the existing data,predict low-ranking nodes,showing that some nodes may be potential cause of congenital microtia,but also need further study.