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Establishment method of genome scar model

A technology for establishing methods and genomes, which can be used in genomics, medical simulation, proteomics, etc., and can solve the problems of repeated counting and expensive detection.

Active Publication Date: 2021-01-01
AMOY DIAGNOSTICS CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above methods have their own limitations. For example, the HRD score is just a simple sum of LoH, LST and TAI. In fact, TAI and LoH overlap in some cases, resulting in double counting. In addition, some CNV types also Not considered by HRD score
Although Davies' model is comprehensive, it requires whole-genome sequencing to count the patterns of various mutation types, resulting in extremely expensive detection costs

Method used

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  • Establishment method of genome scar model
  • Establishment method of genome scar model
  • Establishment method of genome scar model

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039]110 and 18 FFPE samples and control blood samples from ovarian cancer patients were collected as the training set and test set for constructing the genomic scar model. Afterwards, the homologous recombination deficiency (HRD) detection kit of Xiamen Aide Biomedical Technology Co., Ltd. was used for library construction and capture. This kit contains 35 HRR-related genes and 70,000 SNP sites as capture regions. The captured and enriched DNA was finally sequenced on an Illumina Novaseq sequencer.

[0040] The original off-machine data is compared to the human reference genome sequence (version number hg19) through BWA (Li H. and Durbin R.2009). Generate aligned BAM files as input files for mutations and copy number variations. Among them, the Varscan process (Koboldt, D.2012) was used for mutation detection, and the sequenza (FaveroF.2015) process was used for chain-specific copy number variation.

[0041] BRCAness sample confirmation. Select the most common BRCAness ev...

Embodiment 2

[0047] A total of 191 FFPE samples and control blood samples from ovarian cancer patients were collected. Finally, the homologous recombination defect (HRD) detection kit of Xiamen Aide Biomedical Technology Co., Ltd. was used for library construction and capture, and sequencing was performed on an Illumina Novaseq sequencer, and the genomic scar model trained in Example 1 was used Calculate the GSS of the sample to be tested.

[0048] Statistics on the relationship between GSS high grouping and HRR mutation population, as shown in the table below

[0049] No HRR related gene mutation group HRR-associated gene mutation group GSS low grouping 52 19 GSS high grouping 56 64

[0050] Through the hypergeometric distribution test, the high GSS group significantly enriched the patients with HRR-related gene mutations, P=0.0003. In addition, compared with HRR-related genes, the GSS of the genomic scar model obtained in Example 1 can enrich more patien...

Embodiment 3

[0052] The FFPE samples and control blood samples of 44 ovarian cancer patients were collected, and the first postoperative treatment regimen of these patients was platinum-based chemotherapy. Finally, the homologous recombination defect (HRD) detection kit of Xiamen Aide Biomedical Technology Co., Ltd. was used for library construction and capture, and sequencing was performed on an Illumina Novaseq sequencer, and the genomic scar model trained in Example 1 was used Calculate the GSS of the sample to be tested.

[0053] By comparing the progression-free survival (PFS) of patients with high GSS group and low GSS group, the role of GSS in enriching platinum-sensitive populations was evaluated. The result is as figure 1 shown. As shown in the figure, the GSS status, that is, the GSS high score (GSS+) and GSS low score (GSS-) groups, the progression-free survival of patients is significantly different, and the progression-free survival of patients in the high GSS group is signi...

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Abstract

The invention discloses an establishment method and application of a genome scar model, and the establishment method comprises the following steps: (1) collecting known positive samples and negative samples to form a training set; (2) analyzing the conditions of the CNVs in the training set, and determining the types of the CNVs and the corresponding number of the CNVs; (3) determining a BRCAccesspositive event and a BRCAccess negative event; and (4) training to obtain the weights of the different types of CNVs determined in the step (2) through a machine learning method according to a BRCAness positive event and a BRCAness negative event in the training set, and then accumulating the weights of the different types of CNVs to obtain a genome scar model for calculating the GSS. According to the invention, the BRCAness state of the sample to be detected can be accurately predicted, and an interpretation result can be directly given according to the genome scar score.

Description

technical field [0001] The invention belongs to the technical field of gene detection, and in particular relates to a method for establishing a genome scar model. Background technique [0002] Homologous Recombination Repair (HRR) is an important repair method for DNA double-strand damage, and it is common in cells to accurately repair harmful breaks on double-stranded DNA. HRR is a complex signaling pathway involving multiple steps, in which the breast cancer susceptibility gene (BRCA1 / 2) is an important homologous recombination function-related gene. If the BRCA gene mutation leads to the loss of function of BRCA1 and BRCA2 proteins, it will cause abnormal HRR function, which is often called homologous recombination deficiency (Homologous Recombination Deficiency, HRD). HRD, as a tumor driving event, widely exists in breast cancer and ovarian cancer , prostate and pancreatic cancers. Tumors with BRCA1 / 2 mutations or abnormal expression are usually sensitive to platinum-b...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G16B20/20G16H50/50
CPCG16B20/20G16H50/50G16B20/10G16B40/20G16H50/30
Inventor 杨爽董华陈学俊胡靖黄红伟郑方克郑立谋
Owner AMOY DIAGNOSTICS CO LTD
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