Workbench & Pipeline

1. AI shortlist (38.0+)

The AI Shortlist Module, located in the Workbench & Pipeline section of Organization Settings, allows you to refine variant prioritization based on analysis type.

1.1 Rare Diseases

The AI shortlist prioritizes genes of known and unknown significance within the shortlist, which will contain a fixed number (10 SNV, 5 SV) of variants.

• Discovery Mode: The AI shortlist will prioritize known and unknown genes, and will be limited to likely solving variants.

• Focused Mode: The AI shortlist will prioritize known genes and unknown genes separately, and will be limited to likely solving variants.

1.2 Carrier

The AI shortlist will prioritize variants reported as pathogenic or likely pathogenic in any known variant databases or variants with high severity.

• Known Pathogenic: The AI shortlist will prioritize variants reported as pathogenic or likely pathogenic in any known variant databases.

• High Severity: The AI shortlist will prioritize variants with high severity.

• Both: The AI shortlist will prioritize variants reported as pathogenic or likely pathogenic in any known variant databases or variants with high severity.

2. Pipeline versions

To set the versions for the secondary analysis pipeline, case pipeline, DRAGEN, and human reference. An user can also configure whether to include reference homozygous genotype calls in cases. Read more.

2.1. Sample

To set versions for the human reference, DRAGEN, and the secondary analysis pipeline to process individual samples in cases, including mapping alignment and variant calling.

2.2 Variant caller mapping (38.0+)

Manage the variant callers used for the secondary analysis pipeline.

Required role - 'Manage pipeline versions'. Without the role the user will not be able to select/unselect variant callers from the table.

Various variant callers along with the sequencing type, methodology and compatibile sample, dragen and case pipeline version information is shown in the table. Upon save, after selecting the specific varcallers, an user can expect the successive case runs to follow the user selections.

2.3. Sample pipeline arguments (38.0+)

To view your sample pipeline arguments for mapping and calling. If the arguments are not set, they will be displayed as ‘N/A’.

2.4. Case

To set case pipeline version.

3. Organization DB management (38.0+)

To manage your organization’s databases:

1. Go to Organization Settings

2. Select the Workbench & Pipeline tab

3. Scroll to the new section called Organization DB Management

3.1 Viewing Existing Databases

All users can view a table listing the current databases configured for their organization. If no DBs are present, a message will inform you that none are available.

Table Information Includes:

• DB Name

• DB Type (Historic, Noise, or Curated)

• DB File Name

• Human Reference (e.g., GRCh37, GRCh38)

• Variant Type (SNV or CNV)

• Fields:

  • Historic/Noise: AF, HET, HOM, HEM

  • Curated: Pathogenicity

• Overlap Details (for CNVs only):

  • C: Candidate Overlap

  • A: Annotation DB Overlap

  • Example: C: 70%; A: 70%

  • SNVs will show “N/A” in this column

• AI Shortlist: On/Off

• Active: On/Off

• Last Edited Date

Additional Features:

• Search: Use the search bar to filter the table by DB name

• Download: Click the download icon to export a DB as a VCF file

3.2 Adding a New Database

Users with the role Managing Organization DB can add/edit new databases.

Steps to Add a DB:

1. Click Add New in the Organization DB Management section.

2. Complete the form:

   • Active (On/Off)

   • DB Name

   • DB Type: Historic or Noise

   • Variant Type: SNV or CNV

   • Human Reference: GRCh37 or GRCh38

   • AI Shortlist: On/Off

   • Fields will be auto-populated and not editable

3. Upload the DB file using the file browser.

4. Click Save to finalize. A success message will confirm the addition.

Steps to Edit:

1. Click the Edit button next to the database you want to update.

2. Modify the available fields.

3. Click Save to apply the changes. A confirmation message will appear.

Note: Legacy databases cannot be edited. A notification will indicate if a DB is legacy.

3.3 Audit Logging

All changes (adding or editing a DB) are automatically recorded in the organization’s audit log for transparency and traceability.

4. SV annotation threshold (38.0+)

Present under Workbench & Pipeline in Organization Settings, this module enables configuration of annotation overlapping thresholds for structural variants with external and internal databases.

4.1 One Side Pathogenic

CommentShare feedback on the editorThe One Side Pathogenic setting allows to set a threshold for identifying structural variants classified as pathogenic, such as those in ClinGen Pathogenic, ClinVar Pathogenic, DDDSyndromes, and Curate Pathogenic databases. It starts at a default of 0.7, and accepts value between 0 and 1.CommentShare feedback on the editor

4.2 One Side Uncertain

CommentShare feedback on the editorThe One Side Uncertain setting allows to set a threshold for identifying structural variants classified as uncertain, such as those in ClinGen VUS, ClinVar VUS, and Curate VUS databases. It starts at a default of 0.7, and accepts value between 0 and 1.CommentShare feedback on the editor

4.3 Two Sided

CommentShare feedback on the editorThe Two Sided setting allows to set a threshold for identifying structural variants classified as benign, such as those in ClinGen Benign, ClinVar Benign, DECIPHER, DGV, gnomAD SV, 1000 genomes, and Curate Benign databases. It starts at a default of 0.7, and accepts value between 0 and 1.