Homologous recombination defect gene analysis method

Abstract

The invention discloses a homologous recombination defective gene analysis method, which comprises the following steps of: 1, performing quality control and filtering on low-depth whole genome (sWGS) sequencing data by adopting fastp software, comparing the data to a human reference genome by adopting bwa software, sequencing the data according to a chromosome sequence by adopting gatk software, simultaneously marking and removing a repetitive sequence, and comparing the repetitive sequence with the human reference genome; qdnaseq software is adopted to analyze the copy number change in the genome, and shallowHRD software is adopted to evaluate HRD based on the copy number change of the genome and give a score. By accurately evaluating the instability of the genome, the positive detection rate of the homologous recombination defect can be effectively increased, and the detection cost is reduced; meanwhile, the method has the advantages of low time consumption, capability of being used for single sample analysis and the like, and is combined with BRCA1 / 2 gene variation; meanwhile, the depth requirements of gene variation and instability evaluation are met, so that the homologous recombination defect state of a patient is accurately judged, the detection cost is reduced, and the detection economic benefit is improved.

Description

technical field [0001] The invention relates to the technical field of gene analysis, in particular to a homologous recombination defect gene analysis method. Background technique [0002] Homologous recombination deficiency (HRD) is a kind of cancer cell that causes the loss of homologous recombination repair gene function due to various reasons, resulting in the loss of the ability of cells to repair DNA double-strand breaks through homologous recombination (HR), and finally the formation of genome abnormalities. stable state. The BRCA1 / 2 gene is an important gene in the DNA damage repair pathway. Mutations in this gene can inhibit the repair ability of cells after DNA damage and cause homologous recombination deficiency (HRR). In addition to the BRCA1 / 2 gene, other HRR-related genes, such as PALB2, Mutations in CDK12, RAD51, CHEK2, ATM, etc. will cause homologous recombination deficiency (HRD). [0003] More and more patients with ovarian cancer and breast cancer benefi...

AI Technical Summary

Problems solved by technology

However, ovarian cancer patients with BRCA1 / 2 gene mutations only account for about 20%-30%, and adding HRD status assessment on this basis can increase the proportion of homologous recombination-positive patients to 50%, which will greatly increase PARP The potential benefit population of inhibitors, but there are still great difficulties in the evaluation of HRD status. At present, whole genome sequencing (WGS) technology is usually used to evaluate HRD status based on genomic instability for the entire genome. The detection content includes heterozygosity Loss (LOH), Telomere Allelic Imbalance (TAI), and Large Segment Shift (LST)

These methods are technically complex, time-consuming and data-intensive, often require matched normal samples and are costly

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