A Preliminary Study Of Differential Genes And ALK Kinase Resistance And OPN Epitopes In Tumour Microenvironment Based On Bioinformatics

Bioinformatic is a major technology in the life science and medicine field in twenty-first Century.With the development of computer technology,information technology,and biological technology,the researches pay more and more attention to bioinformatics.At present,bioinformatics can make systematic analysis and detailed study of biological events from different levels of genes and proteins,and provides a wider idea for the development of biology,medicine,pharmacy and other fields.In the study,we analyzed the data of acute myeloid leukemia and normal tissue microarray by bioinformatics,and then analyzed the interaction between the differential genes and their proteins by literature mining.Finally,we used the molecular biology experiment to verify the function of the different expression genes.190 different expression genes were screened from acute myeloid leukemia and nomal tissue microarray data.The key genes,NDUFA4(NADH dehydrogenase 1 alpha subcomplex subunit 4),UQCRQ(Ubiquinol-cytochrome c reductase)and COX7A2(Cytochrome c oxidase polypeptide 7A2),were screened by cross network analysis.Functional enrichment analysis showed that the most important part of differentially expressed genes is related to PI3K-AKT signaling pathway.The experimental results indicate that NDUFA4 is the key gene affecting the proliferation of acute myeloid leukemia in the process of PI3 K signaling.The results provide a new idea for the molecular mechanism of acute myeloid leukemia and for its early diagnosis and targeted therapy.Through bioinformatics technology,we studied the mechanism of ALK kinase(anaplasticlymphoma kinase,ALK)resistance.First of all,based on the molecular dynamics simulation,we found the F1174 C mutation disturbed aromatic-aromatic network formed by residues F1098,F1174,F1245 and F1271 in the wild type ALK-ceritinib complex.the resulting mutation allosterically further affected the conformational dynamic of P-loop conformation and caused the upward movement of the P-loop from the ATP-binding site.Subsequently,MM/GBSA combined with free energy calculations and decomposition analysis of binding free energy further verified the F1174 C mutation lead the interaction between ceritinib and ALK to be weaken.This study is expected to contribute to design the next-generation of ALK inhibitors by exploring the mechanistic in the allosteric effect of F1174 C resistance mutation.Bioinformatics technology provides new options for screening antibody epitopes.Firstly,the osteopontin(OPN)antibody and antigen are modeled,and then the possible peptide are optimized and determined by molecular dynamics software.On this basis,using interaction mode between antibody and antigen peptide,we evaluated their the interaction energy and determined the potential epitopes.Finally,we proved that the prediction of antibody epitopes was successful in OPN antibody epitopes,and provides a new idea for computer-aided identification of antibody epitopes.