Question: Recommendations for CNV calling algorithms/programs to benchmark
gravatar for seraphya
3.0 years ago by
seraphya0 wrote:

I want to benchmark the time/resource use and breakpoint accuracy of CNV callers on multiple individual NGS data at 30x-100x coverage at specific CNVs.

A few questions I have:

Is there a specific read mapper I should use to create the BAM file, or should I try a few for each SV/CNV caller?

Are there any specific algorithms/programs I should test? The only one I know I will test for sure is CNVnator as that is what has been used until now.

Anything else I should consider?

cnv assembly • 3.1k views
ADD COMMENTlink modified 3.0 years ago by Garan670 • written 3.0 years ago by seraphya0

Hi, I am doing very similar project - to compare algorithms to detect CNVs. For my best practice I am using BWA aligner. For detection CNV I have good results from - oncoCNV, CNVkit, Pindel.. I did not played with CNVnator - if you can share your experiences everybody would appreciate.

ADD REPLYlink written 3.0 years ago by Paul1.4k
gravatar for Garan
3.0 years ago by
United Kingdom
Garan670 wrote:

I'm guessing you're after germline CNV callers since you've mentioned CNVnator. I've included some suggestions below for read-depth based callers including ExomeDepth which is the one I've used the most (reasonably easy to use since it's an R package). I'd have a look at Ximmer if you're interested in comparing CNV callers since it provides a standardised framework for comparing callers out of the box.

I guess you could try Read-depth callers, callers that look for breakpoints, or split-read (although these are more for WGS than targeted / Exomes), callers that look for missing / moved mate-pairs, or read-pair. There's also assembly based callers and callers that use a combination of the above techniques. The approach you use will also depend on the library and the size of CNV you're looking for.

Generally I've only compared CNV callers after a pipeline that uses BWA for alignment and then GATK best practices, since a couple of the callers actually use parts of the GATK suite (like XHMM). Some CNV callers like CANVAS ( are optimised for their own workflow (in this case ISAAC).

Read-Depth based callers




XHMM XHMM used by ExAC to call their CNVs


ULYSSES Breakdancer




Ximmer Framework for running mulitple CNV callers together and calculating sensitivity etc. Comes with ExomeDepth, Xhmm, Cnmops and Conifer

GATK4 germline CNV caller Not sure if this is available yet but should be ready soon - ideal if you want a full GATK best practice pipeline

Mainly used ExomeDepth on Targeted panels and found it okay with some tweaks and heavy filtering for false positives.

ADD COMMENTlink modified 3.0 years ago • written 3.0 years ago by Garan670

Can Breakdancer be applied on Paired End Whole Exome sequencing data ?

ADD REPLYlink written 3.0 years ago by gsr9999140

GATK4 germlineCNVcaller is available now. It'd be great to see how it stacks up against some of the older methods out there.

ADD REPLYlink written 13 months ago by Matt Miossec350
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