Discovery Of Personalized Tumor Neoantigens Based On RNA-seq And Mass Spectrometry

The conventional therapy of cancer mainly depends on non-personalized therapy like surgical resection,chemoradiotherapy,drug-targeted therapy at present.But these conventional therapeutic strategies have a series of problems such as incomplete treatment and large side effects.Recent studies have shown that tumor immunotherapy by targeting tumor cells through the patient’ s own immune system,personalized neoantigen therapy,has better therapeutic effects in melanoma,breast cancer and other solid cancer.Neoantigens,as specific targets for immunotherapy,are generated by specific mutations in the patient’ s tumor genome.According to this treatment strategy,it is particularly critical to accurately and efficiently discover neoantigens with better expected efficacy among many antigens which can distinguish between tumor and normal tissues.This study developed a novel neoantigen discovery method based on RNA-seq and MS(Mass Spectrometry).In this discovery method,RNA-seq was used to extract neoantigen features and their expression,MS was used to discover MHC(Major Histocompatibility Complex)-binding peptides.The analyze of this two techniques combined can reduce false positive.In addition,based on the extracted 8 kinds of neoantigen features,SVM(support vector machine)was used to construct neoantigen classification model to predict whether neoantigens are immunogenic or not.At last,this discovery method was tested on hepatocellular carcinoma cell lines.One candidate neoantigen was discovered,which is associated with angiogenesis process.In summary,this discovery method can help screen candidate neoantigens and meanwhile reduce the false positives of overall result.At the same time,I expect that this study will help advance research on personalized neoantigen therapy and biomarkers discovery.