How is CNV detection implemented in VarSome Clinical?

We currently offer two types of analyses for CNVs:

      1. For whole exome sequencing (WES) or targeted panel data: The inherent limitation of WES is that it produces reads only covering only the ~2% of the human genome that falls in exons. Therefore, the full spectrum of CNVs and breakpoints may not be completely characterized. In addition, many large CNVs and cross-chromosome events may not be detected. Nevertheless, CNV detection based on WES data may give a quick insight into CNV patterns for a specific disease or phenotype. For more details on the limitations of calling CNVs in such data, please see R. Tan et al., An Evaluation of Copy Number Variation Detection Tools from Whole-Exome Sequencing Data, Hum. Mut.,2014

For such analyses, five or more (ideally, around ten) non-WGS germline or tumor samples from the same sequencing run are required. These will be run as a cohort analysis. CNVs will then be called on each input sample by using the other samples as a control.  All samples will be analyzed together and results for each sample will be shown as a subanalysis of that sample. This type of input is analyzed using the ExomeDepth CNV caller.


      1. For whole genome sequencing (WGS) input: We use the  Delly structural variant caller, an integrated structural variant (SV) prediction tool that can detect both CNVs and other forms of Structural Variants (SV) at single-nucleotide resolution in short-read genomic sequencing data. It combines 3 different approaches (paired-ends, split-reads and read-depth) to discover extensive genomic rearrangements. Two types of SV calling can be implemented using this method:
        1. Germline SV calling: One or more whole genome (WGS) samples, each run as a separate analysis. 
        2. Somatic SV calling: One tumor sample and a matched control (one tumor and one germline) whole genome (WGS) samples, from the same assay, to be run as a Tumour/Normal analysis. 


A step-by-step example on how to run a CNV/SV analysis: 

Firstly, you go to “Launch analysis” drop-down menu at the main VarSome Clinical page and choose “CNV/SV analysis”.


If you go for CNV calling on exome (or targeted panel) data, you should select at least 5 already run analyses from such samples and click on “Start analysis”. 


Each sample’s results will appear as a subanalysis of the main analysis.


If you go for SV calling on genome data, you can choose either:

  1. One or more WGS ran germline sample(s) that will be analyzed separately.
  2. A Tumor/Normal comparison analysis of one tumor and one germline WGS samples