# Copy Number Variation: Methods and Clinical Applications
## 2 Methods of CNV Detection
### Techniques Possibly Affected by the Presence of Undetected CNVs
\begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline
**Tool** & **Description** & **Operating System** & **Availability** & **Reference** \\ \hline \multirow{4}{*}{Canvas SPW} & Canvas SPW & Canvas SPW (Small Pedigree Workflow) is a tool for CNV calling that serves to identify germline and de novo CNVs from pedigree sequencing data. In addition, it infers genome-wide parameters such as cancer ploidy, purity and heterogeneity. & MS Windows Linux & Free-software license & [60] \\ \hline \multirow{4}{*}{MFCNV} & A computational method that (i) considers the intrinsic correlations among adjacent positions in the genome, (ii) calculates read depth, GC-content bias, base quality, and correlation value for each genome bin, and (iii) trains a neural network algorithm to predict CNVs. & NA & Free-software license & [61] \\ \hline \multirow{4}{*}{VarScan 2} & Analysis tool for the detection of somatic mutations and CNVs in exome data from tumor-normal pairs. The algorithm reads data from both samples simultaneously; a heuristic and statistical algorithm detects sequence variants and classifies them by somatic status (germine, somatic, or LOH); while a comparison of UNIX & MS Windows Inc. & Free for non-commercial use & [62] \\ \hline \multirow{4}{*}{ADTEx} & ADTEx & ADTEx (Aberration Detection in Tumour Exome) is a method to infer somatic CNVs and genotypes using WES data from paired tumour/normal samples. The algorithm uses hidden Markov models to predict CNV counts, genotypes, polyploidy, aneuploidy, cell contamination, and baseline shifts. & Linux & Free-software license & [63] \\ \hline \multirow{4}{*}{ReadDepth} & An R package for inferring CNVs from short-read sequencing data. The algorithm uses a statistical model that accounts for overdispersed data and does not require reference sample data. It schemes are method for increasing the resolution from low-coverage experiments by utilizing breakpoint information from paired end sequencing to do positional refinement. For calling somatic CNVs from matched tumor/normal pairs, the authors of ReadDepth recommend a copyCat package that is loosely based on readDepth. & MS Windows Inc. & Free software licence & [64,65] \\ \hline \multirow{4}{*}{CONDEL} & CONDEL (CONsensus DELeteraiousness) is a method for detecting CNVs from single tumor samples using high-throughput sequence data. It utilizes a novel statistic in combination with a peel-off scheme to assess the statistical significance of genome bins, and adopts a Bayesian approach to infer copy number gains, losses, and deletion zygosity based on statistical mixture models. & MS Windows Inc. & \\ \hline \multirow{4}{*}{CNV\_IFTV} & A method that uses a novel isolation forest algorithm and variation-based detection of CNVs from short-read sequencing data. It is a reliable tool even for low-level coverage and tumor purity. & MS Windows Inc. & \\ \hline \multirow{4}{*}{Control-FREEC} & A tool for detection of copy-number changes and allelic imbalances (including LOH) using deep-sequencing data. Control-FREEC automatically computes, normalizes, and segments copy number and beta allele frequency profiles, then calls CNVs and LOH. The control sample is optional for WGS data but mandatory for WES or targeted sequencing data. & MS Windows Inc. & Free software licence & [68] \\ \hline \multirow{4}{*}{EXCAVATOR} & EXCAVATOR (EXome Copy number Alterations/Variations annotATOR) a tool for the detection of CNVs from WES data combines a three-step normalization procedure with a hidden Markov model algorithm and a calling method that classifies Linux & Mac OS X Linux & Freely available & [69,70] \\ \cline{1-1} \cline{2-5} EXCAVATOR2 & genomic regions into five copy number states. EXCAVATOR2 is an enhanced version of EXCAVATOR. It is a read count based tool that exploits all the reads produced by WES experiments to detect CNVs with a genome-wide resolution. & & \\ \hline \multirow{4}{*}{XCAVATOR} & A software package for the identification of genomic regions involved in CNVs from short and long reads in whole-genome sequencing experiments. & Mac Linux & Free-software license & [71] \\ \cline{1-1} \cline{2-5} NA, not available. If applicable, operating systems for individual tools were collected from [[https://bioinformatics.com](https://bioinformatics.com)]([https://bioinformatics.com](https://bioinformatics.com)). If applicable, availability/license information were collected from [[https://github.com](https://github.com)]([https://github.com](https://github.com)) or from the home page of individual tools. & & \\ \hline \hline \end{tabular}
\end{table}