A detection method and quality control system for homologous recombination defects based on ngs platform

Abstract

The invention provides a method for correcting tumor purity in the process of bioinformatics analysis and a method for detecting homologous recombination defects based on an NGS platform. The method of the invention compares the sequencing depth and single nucleotide polymorphism of clinical samples and negative samples in the target region The differences in the allele frequencies of sex loci can be effectively corrected for tumor purity and ploidy, and HRD assessment can be realized.

Description

A detection method and quality control system for homologous recombination defects based on NGS platform technical field The invention belongs to the field of bioinformatics analysis, be specifically related to a kind of homologous recombination defect detection method based on NGS platform (HRDkit) and quality control system. Background technique Homologous recombination deficiency (Homologous Recombination Deficiency, HRD) refers to by BRCA1 / 2 gene Defects in the homologous recombination pathway for repairing DNA double-strand breaks caused by mutation, promoter methylation, and genetic variation. Symptomatic instability is a physical manifestation of HRD. HRD can lead to genomic scarring, including loss of heterozygosity (Loss of Heterozygosity (LOH), Telomere Allelic Imbalance (TAI), and tracts Segment Migration (Large‑scale State Transition, LST). Myriad’s myChoice HRD Test Approved Comprehensive LOH, TAI, and LST scores were measured, and HRD positive was...

AI Technical Summary

Problems solved by technology

[0005] HRD measures the genomic instability in tumor cells, and tumor clinical samples usually contain some normal cells (i.e., tumor purity <100%). If the LOH, TAI, and LST scores are not corrected for tumor purity, the final HRD score is tumor The HRD score of cells and mixed cells cannot truly reflect the HRD status of tumor cells

When the tumor purity gradually decreases, the low copy number CNV (Copy Number Variation, CNV) in tumor cells will be affected by the dilution of normal cells, making the copy number gradually approach the normal state of 2 copies, reducing the HRD score of the sample, Thus affecting the accuracy of HRD test results of clinical samples

At present, the tumor purity assessment of tumor tissue usually uses the histopathological assessment method, which involves cumbersome and complicated experimental procedures and is highly subjective. In addition, for some tumor tissues, the pathological assessment method cannot be routinely used for tumor purity assessment, which will cause Affect the reliability of HRD detection

On the other hand, the current mainstream software for tumor purity detection based on the NGS platform is PureCN and ABSOLUTE, but these bioinformatics algorithm software have limitations in accuracy and application

[0006] In the actual clinical sample detection process, many sample quality factors and experimental processes will affect the accuracy and reliability of HRD detection. source pollution) and affect the accuracy of HRD detection; 2) Similar to the detection of single nucleotide variation / small fragment indel by NGS platform, HRD score will also be affected by sequencing depth, and the decrease of sequencing depth will affect the stability of HRD detection results

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