Method for detecting copy number variation of tumor single-cell genomes

Abstract

The invention discloses a method for detecting copy number variation of tumor single-cell genomes. The method comprises the steps of separately performing genome sequencing on tumor single cells and aplurality of normal tissue single cells, performing comparing with a reference genome, and dividing window and standard window data; and using a normal single-cell comparison as a standard for removing systematic deviation to obtain genome copy number in all tumor single-cell regions. The method disclosed by the invention eliminates some specific system deviation introduced by different single-cell amplifying techniques, so that the accuracy of copy number variation detection of the tumor single-cell genomes can be improved, and the method has important significance in detecting driving incidents relevant with copy number variation and reading tumor genome evolution information.

Description

Technical field [0001] The invention relates to the fields of single-cell genome sequencing, tumor genome analysis and bioinformatics, in particular to a method for detecting the copy number status of tumor single-cell genome based on second-generation sequencing technology. Background technique [0002] Genome sequencing technology has been widely used in basic research in life sciences and some corresponding translational science applications. At present, the second-generation short-sequence sequencing technology based on solexa sequencing technology has demonstrated its wide range of application and huge application prospects. Based on different purposes, we can directly sequence DNA to assemble new species or detect changes in the genome of species with existing reference sequences, such as single nucleotide polymorphism sites (SNPs, singlenucleotide polymorphism), short sequence insertions or deletions (INDEL, insertion and deletion), genome structural variation (SV, struct...

AI Technical Summary

Problems solved by technology

Regardless of the single-cell amplification technology, there will be a certain Allele DropOut (ADO) ratio, and the deviation of the allele amplification ratio and the regional amplification preference greatly limit the resolution of single-cell genome copy number analysis. and accuracy

[0005] Existing methods for analyzing genome-wide copy number changes in bulk cells are not well suited for single-cell studies

However, there are certain problems with single-cell genome copy number change analysis methods.

For example: the method of using dynamic interval window plus GC content correction cannot eliminate some specific biases introduced by different single-cell amplification technology methods; and the single-cell genome copy number analysis method of hidden Markov model often appears overfitting ( overfitting), or the case where the degree of fitting is not high

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