CIRCNV: Detection of CNVs Based on a Circular Profile of Read Depth from Sequencing Data

SIMPLE SUMMARY: In this study, we propose a copy number variation (CNV) detection method called CIRCNV, which is based on a circular profile of the read depth from sequencing data. The proposed method is an extended version of our previously developed method CNV-LOF. The main difference of CIRCNV from CNV-LOF lies in its two new features: (1) it transfers the read depth profile from a line shape to a circular shape via a polar coordinate transformation to generate a meaningful two-dimensional dataset for CNV analysis and promote fairness between the ends and middle part of the genome, and (2) it performs two rounds of CNV declaration via estimating tumor purity and recovering the truth circular RD profile. We test and evaluate the performance of CIRCNV via conducting simulation studies and real sequencing tumor sample applications. The experimental results show that CIRCNV outperforms peer methods with respect to sensitivity, precision, and the F1-score. The experiments prove that the proposed method is a reliable and effective tool in the field of variation analysis of tumor genomes. ABSTRACT: Copy number variation (CNV) is a common type of structural variation in the human genome. Accurate detection of CNVs from tumor genomes can provide crucial information for the study of tumor genesis and cancer precision diagnosis. However, the contamination of normal genomes in tumor genomes and the crude profiles of the read depth make such a task difficult. In this paper, we propose an alternative approach, called CIRCNV, for the detection of CNVs from sequencing data. CIRCNV is an extension of our previously developed method CNV-LOF, which uses local outlier factors to predict CNVs. Comparatively, CIRCNV can be performed on individual tumor samples and has the following two new features: (1) it transfers the read depth profile from a line shape to a circular shape via a polar coordinate transformation, in order to improve the efficiency of the read depth (RD) profile for the detection of CNVs; and (2) it performs a second round of CNV declaration based on the truth circular RD profile, which is recovered by estimating tumor purity. We test and validate the performance of CIRCNV based on simulation and real sequencing data and perform comparisons with several peer methods. The results demonstrate that CIRCNV can obtain superior performance in terms of sensitivity and precision. We expect that our proposed method will be a supplement to existing methods and become a routine tool in the field of variation analysis of tumor genomes.