Rapid and ultrahigh-sensitivity DNA fusion gene detection method

Abstract

According to the DNA fusion gene detection method provided by the invention, on the premise that high-sensitivity detection is not influenced, the operation time is short, high detection specificity is achieved, and meanwhile, fusion gene breakpoints, frequencies and splicing information in DNA sequencing data can be accurately represented.

Description

technical field [0001] The invention relates to the field of bioinformatics analysis, in particular to a bioinformatics analysis method for rapid and ultra-high sensitivity DNA fusion gene detection. Background technique [0002] Genome structure variation usually refers to changes in genome structure longer than 1kbp, mainly including large fragment deletion (Deletion), insertion (Insertion), inversion (Inversion) and translocation (Translocation) [1] . Sequence splicing between different genes caused by genome structure variation is usually called fusion gene. [0003] As an important biomarker, gene fusion provides important information in the diagnosis, prognosis and treatment of tumors. For example, ALK, ROS1, RET gene fusions are often independent oncogenic factors in non-small cell lung cancer and are targets for targeted drug action [2,3] . In the past, the detection of tumor biomarkers was mainly performed on tumor tissue samples. Liquid biopsy is a revolutiona...

AI Technical Summary

Problems solved by technology

[0005] However, the above fusion detection methods have their own advantages and disadvantages.

Based on the method of sequence assembly, the detection effect depends on the quality of the sequence assembly, and it is easy to generate more false positive information, and the method of sequence assembly has the problem of consuming a large amount of computing resources

The method based on the read pair needs to estimate the size of the inserted fragment of the sequencing data and the difference in the distance between it and the read pair, which is likely to cause the problem of false negative and excessive false positive information, and this method can only give the approximate area of ​​fusion

Using split reads to determine the fusion breakpoint is a more accurate method, but in the specific implementation process of different detection methods, there are also problems of insufficient sensitivity and high false positive detection

[0006] In addition, existing fusion discovery methods often perform well in simulated data, but overestimate breakpoints in real tumor genomes in clinical samples, almost all of which suffer from high false positive rates

At the same time, in the case of low proportion of tumor cells, the current detection method has defects in the detection sensitivity of low fusion frequency, and it is difficult to meet the sensitivity requirements of current clinical production, especially liquid biopsy.

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