A method for determining homologous recombination defects based on DNA sequencing data

Abstract

The invention discloses a method for judging homologous recombination defects based on DNA sequencing data, which obtains characteristic attributes; extracts effective data; Attribute processing efficiency, choosing three different base classifiers H 1 , H 2 , H 3 ; for H 1 , H 2 , H 3 Iterative training is performed to obtain an expanded training set, thereby updating the model and completing the training process; using the trained model to label the unlabeled sample set U, and completing the HRD status determination according to the labeling result. The invention solves the limitation of using a single or a small amount of local features such as genomic instability state to determine the HRD state, overcomes the difficulty that the number of samples with known HRD states is very small in clinical practice, and realizes multi-feature attributes under the existing sample data. It can improve the performance of HRD judgment method.

Description

technical field [0001] The invention belongs to the technical field of data science with precision medicine as the application background, and particularly relates to a method for determining homologous recombination defects based on DNA sequencing data. Background technique [0002] Homologous recombination (English name: Homologous Recombination, English abbreviation: HR) refers to the recombination that occurs between non-sister chromatids or DNA molecules containing homologous sequences on the same chromosome or within molecules, and its significance is to repair genes. damage, such as figure 1 shown. If a gene involved in homologous recombination is mutated, it may theoretically affect the homologous recombination process of DNA, and then homologous recombination deficiency (English name: Homologous RecombinationDeficiency, English abbreviation: HRD), also known as HRD positive. In recent years, several studies have reported that HRD can not only be used for cancer di...

AI Technical Summary

Problems solved by technology

The second type of method is affected by factors such as the limitations of cancer types, the baseline of mutation characteristics, and the coverage of point mutation sets. It is still immature and is still in the stage of scientific research and exploration

[0007] Although the first method has been applied in clinical diagnosis, there are still some defects in the clinical practice in our country, the main problem is that the judgment threshold is difficult to determine and optimize

Foundation Medicine's FoundationFocus CDxBRCA LOH assay determines whether HRD is positive based on the LOH value of the tumor genome, but experiments have found that some ovarian cancer patients with low LOH are also HRD positive

MyChoice HRD assay from Myraid is based on high HRD score and BRCA mutation to judge patients as HRD positive, low HRD score and BRCA no mutation to judge patients as HRD negative, and if HRD score fails and BRCA wild type, HRD status cannot be determined

However, changes in LOH and copy number among the features of the HRD score may be caused by rearrangements of chromosomes between non-homologous recombination repairs

In summary, the two existing methods cannot perfectly solve the problem of using local features such as genome instability to determine the HRD status, and there are large errors, and the effect needs to be improved urgently

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