CNV visualization

CNV expected vs observed read coverage plots.

For CNV cohort analyses, VarSome Clinical provides a CNV plot, showing how the observed read depth in the area of the CNV differs from the expected. These plots are generated using a slightly modified version of the ExomeDepth tool.  The plot can be found on its own tab, under the Variant Table. The grey area indicates the 95% confidence interval and the red crosses are specific read depth values at those positions. The location of the  CNV is given by the vertical, dotted lines. Finally, any genes that overlap with the CNV are plotted under the graph. Since there can sometimes be very many genes, making it impossible to plot all of them, we only show the position of the canonical transcript for each gene. Therefore, if a gene has no canonical transcript (e.g. annotated pseudogene) or if its canonical transcript doesn't overlap with the CNV, you may see genes listed in the Variant Table that are not shown in the CNV plot since their canonical transcript isn't the one that overlaps with the CNV.

Observed/expected plot for CNV

In the example above, we can see a duplication, since the observed to expected read depth ratio in the region of the CNV is greater than 1 and above the 95% confidence interval (grey area). Conversely, a deletion would show a ratio smaller than 1 and below the confidence interval.

Quality Score

The quality score is for both WGS and non-WGS. What changes is that for WGS analyses, it is the score of the call as given by delly. For non-WGS analyses, VarSome Clinical implements ExomeDepth. Here, the score is the Bayes Factor, explained in the ExomeDepth documentation as:
It quantifies the statistical support for each CNV. It is in fact the log10 of the likelihood ratio of data for the CNV call divided by the null (normal copy number).
The higher that number, the more confident once can be about the presence of a CNV. While it is difficult to give an ideal threshold, and for short exons the
 Bayes Factor are bound to be unconvincing, the most obvious large calls should be easily flagged by ranking them according to this quantity.
So, while there is no specific threshold we can recommend, since the values will depend on the specific run, you can use the BF score to rank your results.

List of affected exons in CNV analysis

A list of all the affected transcript positions that overlap with each CNV is displayed on the right of the Variant Table, under the "Transcripts" tab.

Reads alignment visualization for CNVs

You can view the alignment of the reads in the regions of the detected CNVs, either on JBrowse or on IGV:


Since you have selected a variant on the Variant Table you can see the alignment of the reads by clicking on the Jbrowse or IGV icon on the top left of the screen.



Browsing through the samples of a CNV analysis

You can now search through the samples analyzed under the same CNV/SV analysis by visiting the results page of one and using the red arrows you can be directed to the next or previous sample: