29 January 2015
Omicia Opal 4.6 is live! This release of Opal includes numerous functional and performance enhancements, with a focus on accelerating comprehensive clinical variant interpretation and report creation.
Opal Clinical provides an end-to-end solution for clinical NGS, combining Omicia’s industry-leading Opal annotation platform with structured interpretation workflows, full support for clinical report generation, and LIS integration -- all within a secure, HIPAA-compliant environment. Contact firstname.lastname@example.org if you’d like to try Opal Clinical.
- New Non-Syndromic Epilepsy Panel
- Interpret Variant Enhancements
- Review Report Summary Field
- Clinical Exome Workflow
1000 Genomes Project Subpopulation Frequencies
In addition to the ExAC and EVS6500 subpopulations, we now have frequencies for the 1000 Genomes Project subpopulations. These are accessible by clicking on the 1KG AF value in Opal Clinical or Variant Miner. The subpopulation frequencies are also available in the Opal Clinical Interpret Variants modal, Additional Annotations tab. If you have an existing sequence you want 1000 Genome Project subpopulation data for, it needs to be re-annotated with Opal Annotation Engine 4.1.1 or greater. Please contact email@example.com. Any newly uploaded sequences are automatically annotated using the latest version.
New Non-Syndromic Epilepsy Panel
Omicia develops Curated Panels to accelerate your panel creation effort. These panels have been curated based on strength of disease association and published guidelines. We just added a non-syndromic epilepsy panel. Included genes for the non-syndromic epilepsy panel, as well as information on our other panels is provided here. The Omicia Curated Panels are available in Panel Builder, under Public Panels. If you want to use any of these panels, click the Actions dropdown menu and select the “Clone Panel” option. Now, it will be available in your Workspace Panels, and can be edited and updated as needed. Note that a clinical report cannot be created off a public panel; you will need to clone the panel before you can use it. Variant Classification now uses "Pathogenic" instead of "Known Pathogenic", to harmonize with ClinVar nomenclature.
Interpret Variant Enhancements
We have simplified the interpretation workflow for panels and family tests, removing the Select Variants page so all interpretation work takes place in the Interpret Variant page. We have also added a number of capabilities to accelerate variant interpretation and write the variant description for a clinical report.
- Template Text in Variant Description. The Variant Description field is pre-populated with template text, which you can edit. The template text is structured as follows: "This patient is <genotype> for variant <variant HGVS notation> in the <gene> gene. <RefSeq gene description.>"
- Copy ClinVar evidence. ClinVar evidence and classifications are provided in the Interpret Variant modal, Variant Evidence tab. Using the "Copy Variant Interpretation and Description" button, you can copy the ClinVar classification, condition, citation, and related abstract into your variant interpretation. The abstract replaces any text in the Variant Description field.
- Previously Seen variants. If a variant was classified or reviewed in previous patient samples within your institution, it will show up in the Interpret Variant modal, Previously Seen tab. You can copy the classification and variant description from a previous report, or view the report itself to compare to the current case. If you Copy Interpretation from a previous report, it will replace the pre-populated template text in the Variant Description field.
Additional enhancements include: IGV Integration. We have integrated with the Integrative Genome Viewer (IGV) to view data from BAM files, allowing you to assess the quality of an alignment or a region. The IGV link launches the desktop version of IGV, and needs to be configured by your workspace admin. The IGV link is displayed in the Interpret Variant table. Omicia Score. We have added four colored squares underneath the Omicia score to denote the individual evaluations of the underlying component scores. The range is Red-Yellow-Green, with red deleterious and green benign. This provides insight into the concordance of the underlying scores. You can also click on the Omicia score for the individual scores and descriptions. Citations. Now, we support inclusion of citations from Panel Disease Associations, and designation of secondary citations. Previously, citations were associated with a variant when it was annotated in Opal Annotation Engine or the variant was curated in Panel Builder. Now, we also pull in citations from Panel Disease Associations. As before, you can also add citations manually by adding PMIDs. Citations can be designated as Primary or Secondary, though only one citation per variant can be Primary. Track number of reviewed Variants. The Interpret Variant modal displays the number of reviewed and total variants in the report, enabling you to track progress as you are interpreting variants. A variant with status of Reviewed, To Be Confirmed, Confirmed or Failed Confirmation will count as a reviewed variant. Condition. If conditions are provided in Variant Evidence or Panel Disease Associations, they will be presented in a Condition dropdown menu when the user starts typing in the field. Gene Viewer. The Gene Viewer has been enhanced with unzoom and arrow buttons allowing you to navigate the gene more easily. To zoom, click and drag the mouse right to highlight the section you want to zoom in on. In addition, when you click on a variant in the Gene Variants tab, the gene viewer recenters around that variant. The Gene Viewer can be accessed by clicking on a gene name in the Interpret Variant table.
Review Report Summary Field
There is now an Update button for the Summary field in the Review Report page. This Update button will replace the current Summary field information with the Variant Descriptions. This can be useful in cases where you decide to add another variant to your interpretation and want to pull in the variant description, or when you simply want to restart writing your summary.
Clinical Exome Workflow
The Exome Workflow in Clinical Reporter has been updated. Now, when you set up the Exome test, you do not specify a filter. Instead once the set up the test, you are presented with a clinical version of Variant Miner, which allows you to use Variant Miner's rich filtering capabilities to select variants for your clinical exome interpretation.
Workspace Administration and Navigation
We have added the workspace name to the navigation breadcrumb at the top of each, to clarify which workspace a user is working in. We have expanded the capabilities of the Workspace Admin, and centralized these in Admin Settings accessible from the Workspace dropdown menu. Now, a Workspace Admin can:
- Administer users on projects and their level of access
- Administer workspace members and their level of access
- Manage Payment Accounts
- Manage Workspace Info
- Configure IGV integration
We have also simplified project roles into Contributor and Viewer. Contributor has replaced Owner and Member roles, and has the same responsibilities as the two roles combined. In addition, the default sharing setting for Projects has been changed, so projects are not shared with everyone in the workspace by default. You need to add users to projects to provide access. To share a new project with all members of a workspace, you need to select the "Share project with everybody in the workspace" checkbox.
Synonymous variants are now notated in 3-letter protein HGVS nomenclature instead of 1-letter HGVS. The HGVS is annotated in the pipeline, so existing sequences needs to be re-annotated with Opal Annotation Engine 4.1.1 or greater. Any newly uploaded sequences are automatically annotated using the latest version.
Opal Annotation Engine - N Alleles
Alleles that are unspecified, showing up as an "N" in the VCF, are now annotated as three separate alt alleles.
Data Source Release Versions
- dbSNP release 142
- Exome Variant Server version 6500
- ExAC November release
- ENSEMBL version 75
- ClinVar (downloaded 1/2015)
- HGMD Public version 7.1
- OMIM (downloaded 11/13/2014)
- PharmGKB (downloaded 1/2010)
- 1000 Genomes phase 1 release (downloaded 12/2011)
- PhenCode (downloaded 05/2013)
- GWAS catalogue (downloaded 05/14/2014)
- dbNSFP version 2.5