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

A technology of tumor antigen and prediction method, applied in the field of bioinformatics, which can solve the problems of incomplete assessment of tumor antigen load, not necessarily expressed mutations, incomplete mutation detection, etc.

Pending Publication Date: 2019-05-24
上海鲸舟基因科技有限公司
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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 antige

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

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Embodiment 1

[0145] In this example, a pair of non-small cell lung cancer samples' tumor-adjacent whole-transcriptome sequencing data was used as input, and a total of 15 tumor-associated antigen genes, 3 tumor-specific gene fusions, and 488 tumors with protein coding capabilities were detected. novel transcripts and 127 somatic mutations in protein coding regions.

[0146] Table 1, Table 2, Table 3, and Table 4 respectively show the detailed information of tumor-associated antigen genes, gene fusions, novel transcripts, and somatic mutations. Due to space limitations, only the top20 are taken as examples.

[0147] Table 5 lists the detection results of four different HLA molecular typing tools Seq2HLA, OptiType, arcasHLA and hla-genotyper, A*31:01, B*40:01, C*07:02 have high consistency Allele was used for tumor antigen affinity prediction for this sample. Taking the affinity lower than 500nM as the cutoff, a total of 1376 tumor antigens were screened, that is, the overall antigen load o...

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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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Application Information

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IPC IPC(8): G16B20/50G16B25/10G16B30/10G16B40/00
CPCY02A90/10
Inventor 叶浩李祥永韩子维黄建锋戴珩
Owner 上海鲸舟基因科技有限公司
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