11. Making a Project TemplateΒΆ

The original fitlers we applied to this project were designed to provide us with good example variants to evaluate. Let’s update the filter chain to simply provide a list of high quality variants that have some evidence of being Pathogenic based on the ACMG Sample Classifier auto-scoring algorithm.

First, we will right click on the last two filters in our filter chain (based on the All MAF and ClinVar Classification fields) and click Delete. The ACMG Sample Classifier will contain much more advanced criteria based on population frequency and ClinVar than these filters provide.

Next, let create a filter based on the auto-scoring classification and our classification from previous sample’s interpretations. To do this, scroll the table to the ACMG Sample Classifier output, then right-click on the column header, Classification, and selecting, Add to Filter Chain.

ACMG classification results

Figure 11-1: The ACMG Classification results close-up.

Now we will select every Classification that has some Pathogenic criteria of interest and no overwhelming Benign criteria. This includes of course Pathogenic and Likely Pathogenic categories, but also should include Variants of Uncertain Significance (VUS). The ACMG Samples Classifier algorithm helpfully partitions all VUS variants into three groups:

  • VUS/Weak Pathogenic: Only Pathogenic criteria scored, but not enough to make Likely Pathogenic
  • VUS/Conflicting: Some Pathogenic, but also some Benign criteria scored
  • VUS/Benign: Only Benign criteria scored, but not enough to make Likely Benign

As a hard filter, we can be select all categories other than those that meet the criteria for Benign, Likely Benign or most likely VUS/Benign without ever dismissing clinically actionable variants. In this project, we now have only 9 variants as candidates after this filtering.

ACMG classification results

Figure 11-2: The Filter Chain with the ACMG Algorithm Classification filter

Finally, if we want to repeat all of these steps with data from a new set of samples, VarSeq supports saving any project as a Project Template that allows you to recreate the exact same project with a new set of input VCFs.

Simply go to File > Save Project as Template... and provide a new for the template and optionally some documentation for users who will see it in the New Project dialog.