3.7.5. Manage Gene List Dialog

The Manage Gene List Dialog allows you to define and edit custom virtual gene panels. These gene panels can then be used by the algorithms and filter chain in VarSeq as well as in VSClinical.

To create, update and manage gene lists (gene panels) go to Tools > Manage Gene Panels.

These gene panels are independent of any specific project and are stored in a customizable gene panel library. New panels can be easily added to this library using the gene lists supplied by PanelApp or through gene-phenotype associations in the HPO and MONDO ontologies.

Gene Panels

The Gene Panels section displays the current list of panels in the gene panel library. By default, this list will include multiple versions of the ACMG Secondary Findings panels.

Manage Gene Panels

To view the details associated with any panel in the library, simply click on the panel name in the list. Once a panel has been selected, we can view the details for each included gene by scrolling to the Gene Details section. This section includes a table containing information about each gene including the gene ids, preferred transcript, genomic coordinates, aliases, and detailed name.

Gene Details

To edit the genes in a gene list, click the edit button in the upper right corner of the edit section. This will allow you to enter a list of genes. When finished click the validate button, this will look up each of the entered genes in the latest gene track for the assembly of the project that is currently open. If a gene can not be found an error is displayed below the gene entry box. To save the changes to the gene list, the genes that were not found must be removed or corrected.

There are three ways to add a new gene list:

  1. New Gene List : This button will clear the current selection and allow you to create a new gene list by hand.

  2. From Panel App…: This button will allow you to import a gene list from the [PanelApp]( https://nhsgms-panelapp.genomicsengland.co.uk/panels) knowledge base.

  3. From Phenotypes: This button will allow you to lookup gene associations from a list of phenotypes.

New Gene List

A new panel can be created by clicking on the New Panel button. This will allow you to manually specify the panel information along with a comma separated list of gene names to be included in the panel. While this method works well when have an already established list of genes, you will often want to create panels targeting specific disorders or phenotypes.

From PanelApp

When dealing with disorders that have well-established gene associations, you will most likely want to use the From PanelApp tool. This tool can be used to search the PanelApp knowledge base for existing panels related to a specific disorder.

PanelApp is a publicly available knowledge base of gene panels related to human disorders. PanelApp contains gene lists for a wide variety of disorders and each panel is versioned and validated by experts in accordance with a strict curation process.

Each gene is classified into one of three status categories based on the level of available evidence:

  • Green: These genes are considered diagnostic-grade and require evidence from three or more unrelated families or from two families where there is strong additional functional data.

  • Amber: Genes with this status are associated with borderline evidence.

  • Red: These genes are associated with a low level of evidence.

You can search the PanelApp knowledge base by entering a disorder into the search bar at the top of this dialog or you can simply select one of the commonly used panels from the list provided. Once a panel has been selected, click the blue button in the right hand corner of the window to create a new panel with the selected genes.

From Panel App

After adding the genes associated with a specific disorder in PanelApp, we can customize the panel by editing the name, URL, description, or by adding and removing genes.

From Phenotypes

VarSeq also supports the creation of gene panels based on the gene-phenotype relationships in the HPO and MONDO ontologies. Clicking the From Phenotypes button will launch the Genes from Phenotypes panel creation window.

From Phenotypes

From this window, you can enter a list of HPO and MONDO phenotype/disorder terms and lookup genes associated with these terms, either directly or through association with more general upstream nodes in the ontology. The associated genes can then be used as a starting point for the creation of phenotype-specific gene panels.