A method to improve the detection effect of large CNV in small panel data

Abstract

The invention discloses a method for improving the detection effect of large-scale CNV in small panel data. By introducing several control genes (such as common housekeeping genes) that are irrelevant to the clinical phenotype of the gene to be detected and have stable copy numbers when designing the small panel, The ratio of the CNV interval expected to appear after adding the control gene to the total design length of the Panel becomes smaller, preferably less than 20% of the total design length of the Panel, thereby reducing the impact of large CNVs on the detection of CNV signals by the CNV detection software based on the coverage distribution of sequencing data, This enables large CNVs to be detected normally.

Description

technical field [0001] The invention relates to the technical field of genome variation detection in biology and precision medicine, in particular to a method for improving the detection effect of large CNV in small PANEL data. Background technique [0002] Gene detection panel refers to biological detection kits and corresponding analysis methods used to detect gene mutations in genes or genomic regions associated with a specific disease. High-throughput sequencing technology (High-throughput sequencing), also known as "next-generation" sequencing technology (NGS), can sequence and sequence hundreds of thousands to millions of DNA molecules in parallel at one time. Generally, the read length is shorter and so on as a sign. In recent years, with the rapid development of high-throughput sequencing technology and the reduction of sequencing costs, more and more medical fields are designing panel kits based on NGS sequencing platforms to detect specific genes to detect or scre...

AI Technical Summary

Problems solved by technology

[0009] 3) The existence of large-scale copy number variation will lead to significant changes in the distribution of sequencing data in the small Panel design area, destroying the coverage correlation between the target sample with copy number variation and the reference sample without copy number variation, thus affecting Detection of Copy Number Variations Causes Difficulties

[0010] 4) In an extreme case, if the genes designed in the small panel are deleted as a whole, the signal of copy number variation in the data will disappear, and the copy number variation detection method based on coverage difference will be completely invalid

However, when a large indel occurs, such as figure 1 The DEL that appeared on the TSC2 gene, because the CNV region is too large, breaks the balance of the reads distribution, and the CNV detection software mistakenly regards the reads coverage of 5000X as a normal copy number, while some regions of the TSC1 gene and TSC2 gene are due to the coverage. Above 5000X, the CNV detection software mistakenly thinks that there is a false positive of DUP

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