Single nucleotide variants (SNVs) are very common in human genome and pose a significant effect on cellular proliferation and tumorigenesis in various cancers. Somatic variant and germline variant are the two forms of SNVs. They are the major drivers of inherited diseases and acquired tumors respectively. A reasonable analysis of the next generation sequencing data profiles from cancer genomes could provide crucial information for cancer diagnosis and treatment. Accurate detection of SNVs and distinguishing the two forms are still considered challenging tasks in cancer analysis. Herein, we propose a new approach, LDSSNV, to detect somatic SNVs without matched normal samples. LDSSNV predicts SNVs by training the XGboost classifier on a concise combination of features and distinguishes the two forms based on linkage disequilibrium which is a trait between germline mutations. LDSSNV provides two modes to distinguish the somatic variants from germline variants, the single-mode and multiple-mode by respectively using a single tumor sample and multiple tumor samples. The performance of the proposed method is assessed on both simulation data and real sequencing datasets. The analysis shows that the LDSSNV method outperforms competing methods and can become a robust and reliable tool for analyzing tumor genome variation.

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.

Copy number variation (CNV) detection based on second-generation sequencing technology is the basis of much gene research, but the read depth is affected by mapping errors, repeated reads, and GC bias. The existing methods have low sensitivity to variation regions with a short length and small variation range. Therefore, it is necessary to improve the sensitivity of algorithms to short-variation fragments. This study proposes a new CNV-detection method named WAVECNV to solve this issue. The algorithm uses wavelet clustering to process the read depth and determine the normal cluster and abnormal cluster according to the size of the cluster. Then, according to the distance between genome bins and normal clusters, the outlier of each genome bin is evaluated. Finally, a statistical model is established, and the p-value test is used for calling CNVs. Through this method, the information of the short variation region is retained. WAVECNV was tested and compared with peer methods in terms of simulated data and real cancer-sequencing data. The results show that the sensitivity of WAVECNV is better than the existing methods. It also has high precision in data with low purity and coverage. In real data experiments, WAVECNV can detect more cancer genes than existing methods. Therefore, this method can be regarded as a conventional method in the field of genomic mutation analysis of cancer samples.