Identify Causal Inherited Variants in Family of Four (WGS)

This workflow has been deprecated and will be retired in a future version of the software. It has been moved to the Legacy Workflows (Image legacy_wf_folder_closed_16_n_p) folder of the Toolbox, and its name has "(legacy)" appended to it. If you have concerns about the future retirement of this workflow, please contact QIAGEN Bioinformatics Support team at

As the name of the workflow implies, you can use the Identify Causal Inherited Variants in a Family of Four (WGS) (legacy) template workflow to identify inherited causal variants in a family of four. The family of four consists of an affected child, its parents, including one affected by the condition, and one additional affected family member where (sibling, grand parent, uncle or the like).

To run the Identify Causal Inherited Variants in a Family of Four (WGS) (legacy) workflow, go to:

        Toolbox | Template Workflows | Legacy Workflows (Image legacy_wf_folder_closed_16_n_p) | Identify Causal Inherited Variants in a Family of Four (WGS) (legacy) (Image causal_inherited_variant_four_wgs_legacy_16_n_p)

  1. Double-click on the Identify Causal Inherited Variants in a Family of Four (WGS) (legacy) workflow to start the analysis. If you are connected to a server, you will first be asked where you would like to run the analysis.

  2. The trimmed sequencing reads from the different family members are specified one at a time in successive dialogs (figure 26.15).

    Image reads_iciv4_wgs
    Figure 26.1: Specify the trimmed sequencing reads for the appropriate family member.

  3. Select which reference data set should be used to identify causal inherited variants (figure 26.16).

    Image identify_causalinherited_variants_wgs
    Figure 26.2: Choose the relevant reference Data Set to identify causal inherited variants.

  4. Specify the Hapmap populations that should be used for filtering out variants found in the Hapmap database (figure 26.17).

    Image removehapmap_icivwgs
    Figure 26.3: Select the relevant Hapmap population(s).

  5. Similarly, specify the parameters for the Fixed Ploidy Variant Detection tool for each family member successively (figure 26.18).

    The parameters used by the Fixed Ploidy Variant Detection tool can be adjusted. We have optimized the parameters to the individual analyses, but you may want to tweak some of the parameters to fit your particular sequencing data. A good starting point could be to run an analysis with the default settings.

    Image fp_settings_iciv4_wgs
    Figure 26.4: Specify the parameters for the Fixed Ploidy Variant Detection tool.

    The parameters that can be set are:

    • Required variant probability is the minimum probability value of the 'variant site' required for the variant to be called. Note that it is not the minimum value of the probability of the individual variant. For the Fixed Ploidy Variant detector, if a variant site - and not the variant itself - passes the variant probability threshold, then the variant with the highest probability at that site will be reported even if the probability of that particular variant might be less than the threshold. For example if the required variant probability is set to 0.9 then the individual probability of the variant called might be less than 0.9 as long as the probability of the entire variant site is greater than 0.9.
    • Ignore broken pairs: When ticked, reads from broken pairs are ignored. Broken pairs may arise for a number of reasons, one being erroneous mapping of the reads. In general, variants based on broken pair reads are likely to be less reliable, so ignoring them may reduce the number of spurious variants called. However, broken pairs may also arise for biological reasons (e.g. due to structural variants) and if they are ignored some true variants may go undetected. Please note that ignored broken pair reads will not be considered for any non-specific match filters.
    • Minimum coverage: Only variants in regions covered by at least this many reads are called.
    • Minimum count: Only variants that are present in at least this many reads are called.
    • Minimum frequency: Only variants that are present at least at the specified frequency (calculated as 'count'/'coverage') are called.

  6. In the last wizard step you can check the selected settings by clicking on the button labeled Preview All Parameters. In the Preview All Parameters wizard you can only check the settings, and if you wish to make changes you have to use the Previous button from the wizard to edit parameters in the relevant windows.

  7. Choose to Save your results and click on the button labeled Finish.

Output from the Identify Causal Inherited Variants in a Family of Four (WGS) (legacy) workflow

The following outputs are generated: