Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Tumor neoantigen detection method, device and storage medium based on next-generation sequencing

A technology for antigen detection and next-generation sequencing, which is applied in biochemical equipment and methods, microbial measurement/inspection, genomics, etc., and can solve problems such as false positives, false positives in high-quality neoantigen screening, and failure to consider mutant peptides , to achieve the effect of reducing false positives

Active Publication Date: 2022-04-08
深圳裕策生物科技有限公司
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, EpiToolKit does not consider the comparison between mutant peptides and normal peptides. High-quality neoantigens generally have a higher affinity for mutant peptides than normal peptides. EpiToolKit lacks such a comparison, which will also cause high-quality neoantigen screening. false positive
[0005] Epi-Seq only predicts tumor-specific antigens from tumor expression data, and predicts neoantigens from expression data, which will also cause false positives
On the one hand, it is easy to cause false positives due to the influence of RNA editing; on the other hand, because RNA sequencing is sequenced after reverse transcription from cDNA, this process will also introduce a large number of false positives; on the other hand, tumorcDNA VS Germline DNA will have a lot of false positives in the detection method
The above factors lead to more false positives in the neoantigens obtained by Epi-Seq
[0006] Therefore, there is currently no method and process for screening high-quality tumor neoantigens from multiple perspectives directly from the sequencing comparison results

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Tumor neoantigen detection method, device and storage medium based on next-generation sequencing
  • Tumor neoantigen detection method, device and storage medium based on next-generation sequencing
  • Tumor neoantigen detection method, device and storage medium based on next-generation sequencing

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] This example uses Yadav, Mahesh, et al. * # * Predicting Immunogenic Tumour Mutational and Exme Sequencing. * # * Nature 515.7528 (2014): 572. Data from Document (hereinafter referred to as Document 1): Mouse Model MC-38 tumor sample and normal sample exterior data, and transcript data; adoption of second-generation tumor new antigen detection method, the tumor new antigen detection, as follows:

[0096] (1) Variation test

[0097] Insertion and deleion, Indel are detected by Varscan and Mutectide, SINGLE NUCLETIDE VARIANT, SNV. In order to obtain high quality mutations, the intersection of two software is used as high quality candidate mutations. For the detection of the fusion gene, STAR-Fusion is applied to detect comparison RNA BAM format files.

[0098] (2) MHC molecular identification

[0099] In order to examine the type of MHC-I and MHC-II molecules, this example uses Polysolver to detect the HLA molecular type of normal samples and tumor samples. If the HLA molecul...

Embodiment 2

[0134] 利用发表数据ICC24(Sia D,Losic B,Moeini A,et al.Massive parallelsequencing uncovers actionable FGFR2-PPHLN1fusion and ARAF mutations inintrahepatic cholangiocarcinoma.[J].Nature Communications,2015,6:6087-6087.),采用实施例1 Tumor neovascular antigen detection method for new antigen detection. The results showed that 5 antigen peptides identified by HLA were detected, including the high frequency of the ICC, which can be identified by HLA-01, derived from the fusion gene FGFR2-pphln1 of hepatic cholangiocarcinoma. It can be seen that the new tumor new tumor neovascular antigen in cholangiocyte carcinoma is found using the tumor new antigen detection method of Example 1. There is no good treatment for advanced biliary cell carcinoma, the survival rate is low; the new antigen has been obtained by the method of Example 1, and the new type of treatment of biliary cell carcinoma is found, which provides a new solution for the treatment of biliary cell carcinoma. And the way.

Embodiment 3

[0136] Application This method is used for new antigen detection of 288 liver inner bile duct cancer (ICC) samples, 288 liver bile duct cancer samples from the following 4 documents:

[0137] Hiromi Nakamura, Yasuhito Arai1, Yasushi Totoki, et al.genomic spectraof biliary tract can, [j] .nature menetics, 2015, 47 (9): 1003.

[0138] .

[0139] Yuchen Jiao,Timothy M Pawlik,Robert A Anders,et al.Exome sequencingidentifies frequent inactivating mutations in BAP1,ARID1A and PBRM1 inintrahepatic cholangiocarcinomas.[J].Nature Genetics,2013,45(12):1470-U93.

[0140] Sikiş sikiş sikiş sikiş sikiş sikiş 05:

[0141] The analysis results of 18,813 non-synonymous mutations of 288 ICC samples show that each ICC sample can find 22.8 mutant antigen peptides recognized by high-frequency HLA genotypes in the population, with 62% of Clonalmutation. Note These samples can be treated in patients when there is no suitable targeted drug.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present application discloses a method, device and storage medium for detecting tumor neoantigens based on next-generation sequencing. The tumor neoantigen detection method of the present application includes a variation detection step, an MHC molecular identification step, a variation annotation step, a mutant peptide prediction step, a mutant peptide MHC / Type II affinity prediction step, an antigen expression abundance detection step, and clonality analysis step and the step of comprehensive scoring and sorting of candidate tumor neoantigens; wherein, the step of comprehensive scoring and sorting of neoantigens includes scoring and sorting the neoantigens according to Equation 1 according to MHC affinity, antigen expression abundance and clonality. The tumor neoantigen detection method of the present application directly detects mutations and MHC based on the comparison files of next-generation sequencing, and analyzes candidate tumor neoantigens from the three dimensions of MHC type I / II affinity, antigen expression abundance, and clonality Scoring is performed to screen out high-quality tumor neoantigens, which lays the foundation for immunotherapy based on tumor neoantigens.

Description

Technical field [0001] The present application relates to the field of tumor new antigen detection, and in particular, a tumor new antigen detection method, apparatus, and storage medium based on second-generation sequencing. Background technique [0002] Tumor-Specific Antigens (abbreviation TSAS) refers to an antigen (NeoantiGens) unique to tumor cells. The tumor-specific antigen is proposed in the first half of the last century, and then with molecular biology development and the in-depth understanding of the main tissue compatibility complex (Major Histompatibility Complex, abbreviation MHC) molecular function, Boon et al. First discovered in tumors. The specific peptide segment and MHC molecular complexes produced by tumors can be identified by CD8 + or CD4 +. Subsequent studies recognize that these antigens identified by T cells come from genomic variations of tumors to neo-epitopes, which are defined as new antigen (neoantiges). Unlike tumor-related antigen, tumor-specific...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6869C12Q1/6886G16B20/50G16B30/00
CPCC12Q1/6869C12Q1/6886C12Q2600/156C12Q2535/122
Inventor 王佳茜高志博陈龙昀李淼
Owner 深圳裕策生物科技有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com