Tumor antigen prediction method based on whole transcriptome, and application of the same

Abstract

The invention relates to a tumor antigen prediction method based on a whole transcriptome. The tumor antigen prediction method includes the steps: respectively performing protein generation and peptide fragment interception of tumor-associated antigen, detection of tumor somatic mutation and corresponding mutant peptide fragment interception, generation of tumor-specific novel transcript and peptide fragment interception, and gene fusion detection and fusion peptide fragment interception in tumor tissues, according to the whole transcriptome sequencing data of tumor tissues and corresponding adjacent para-carcinoma tissues, obtaining tumor-associated antigen, tumor somatic mutation, tumor novel transcript, tumor-specific peptide fragment of gene fusion, calculating affinity of the obtainedtumor-specific peptide fragment and the HLA molecule and the amount of expression in each transcript, and based on the affinity value of the tumor-specific peptide fragment and the amount of expression TPM (transcripts per million) value, evaluating the level of the candidate tumor antigen. The invention also provides an application of the same. The tumor antigen prediction method based on a whole transcriptome and the application of the same are conductive to accurate calculation of the tumor antigen load, evaluation of immunological therapy effect, and tumor vaccine design of the later stage of service.

Description

technical field [0001] The present invention relates to the field of biological information, in particular to the discovery of biomarkers for tumor immunotherapy, specifically a method for predicting tumor antigens based on the whole transcriptome and its application. Background technique [0002] Tumor antigens generally refer to new neoantigens or overexpressed tumor-associated antigens in the process of tumorigenesis and development. [0003] Among them, emerging antigens are also called neoantigens, which are mostly derived from mutant proteins that do not exist in normal cells formed by mutations in the tumor genome, including SNV / Indel, gene fusion, and alternative splicing. For the body, neoantigens are specific new proteins expressed by tumors, which can mediate immune cells to accurately recognize and kill tumors without accidentally killing other normal tissues. [0004] Tumor-associated antigens are derived from proteins that are abnormally highly expressed in tu...

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Problems solved by technology

[0007] There are three defects in the above sequencing steps: a) The mutation detection is not complete. Due to the limitation of the capture region of the whole exon, for example, most of the gene fusions and alternative splicing occur in the non-coding region, so the whole exon The novel transcripts formed by these gene fusions and alternative splicing cannot be fully detected; b) The detected mutations may not necessarily be expressed. Tumor antigens are finally recognized with HLA at the protein and polypeptide level. Whether these mutations can be expressed It is a key link, but the mutation in the protein coding region detected on the whole exome sequencing cannot determine whether the mutation is actually expressed; c) The tumor-associated antigen formed by the change of the restricted expression pattern of the gene is ignored, so that the overall tumor Antigen load assessment is incomplete

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