Golden Helix is excited to spread the word about our partnership with Genomenon, a genomic intelligence giant! We recently presented a joint webcast featuring Dr. Nathan Fortier, Director of Research, Dr. Rana Smalling (Field Application Scientist), members of the Golden Helix team, and Denice Belandres (Senior Manager of Customer Success) from the Genomenon team. This webcast demonstrated how VarSeq integrates Genomenon Mastermind and Genomenon Cancer Knowledgebase (CKB), enhancing germline and somatic variant analysis and clinical reporting.
Denice Belandres introduced the Genomenon genomic intelligence platform for clinical diagnostics and precision therapeutic development. She reviewed the key statistics highlighting the breadth of genomic information curated or indexed in Genomenon Mastermind and CKB. She also gave insights into how each resource was curated and how users can explore the data through the Genomenon web user interface (UI).
Dr. Nathan Fortier discussed how Golden Helix has implemented Genomenon Mastermind Curated Variants and Indexed Variants annotations, and how the data from the Curated Variants track, which includes expert-curated ACMG classifications, can be seamlessly incorporated into VSClinical ACMG as an additional source of variant classifications for inclusion in clinical reports.
Dr. Rana Smalling then reviewed how VarSeq now incorporates Genomenon CKB Variant Evidence (for small variants), Region Evidence (for copy number variants), and Fusion Evidence tracks (for fusions or breakends) and how users can easily pull this information into VSClinical AMP to provide current insights on targeted therapies with FDA approval or based on professional guidelines.
We wanted to follow up on several questions that were asked by our attendees that we did not get the chance to address in detail during the live broadcast:
Question: If a variant is not curated or known in Genomenon CKB, does VarSeq pull out a second category variant or the best match? For example, a BRCA2 missense variant, a BRCA2 activating mutation, etc.
When searching clinical evidence, VSClinical always incorporates the more general variant categories covered by the CKB Region tracks (such as BRCA2 missense) alongside evidence directly associated with the specific variant being evaluated.
Question: How can I see the literature that supports fusion evidence in VarSeq?
Within the VSClinical AMP guidelines tool, citations can be viewed on an individual biomarker basis in the Variants>SVDetails section for the primary or secondary gene of a gene fusion. In-line references for drug sensitivity interpretations can also be viewed in the Clinical Evidence tab. Each of these references listed can be expanded to view the publication abstract and access links to the full text on PubMed.
Question: Does Genomenon Mastermind have CNVs and fusions as well?
You can search for CNVs and fusions in the Genomenon Mastermind UI. These are not yet manually curated, but the literature is available in the Mastermind database, and a user can access and view this data, including article sentence fragments on the Genomenon web interface. This would require a separate license, as the focus of the curated data available in VarSeq is single-nucleotide variants.
Question: What if I only want to see Genomenon CKB Tier 1 evidence in VSClinical AMP?
The Add Interpretation from Genomenon CKB evaluation script, which is used to pull in evidence from the Variant Evidence, Region Evidence, and Fusion Evidence tracks, pulls data from Tiers I and II by default. However, the user can easily modify the script to only pull in Tier I level evidence by adjusting the lines of code that stipulate what tier levels to import.
Question: How many variants are there in the Mastermind Curated Variants? Does every variant in the Mastermind database with literature evidence also have a classification? How frequently are the Mastermind and CKB databases updated through VarSeq? Do you have any estimation about the percentage of VUS that can be reclassified as LP/P or LB/B with the help of Mastermind data?
The Genomenon Mastermind curation process is ongoing, and updates occur rapidly. Please contact us at support@goldenhelix.com for specific comments on these statistics.
Question: Is there a difference in the license for Mastermind through VarSeq or a separate license for the Mastermind platform regarding the content that can be accessed?
There are two parts to Genomenon Mastermind data – indexed variants and manually curated evidence, which are included in VarSeq. One additional use case of the indexed variants track that was not mentioned in the webcast is for automating the negatives. This refers to using a missing or zero article count to deprioritize a variant. These features are available in VarSeq through the Golden Helix licensing system. Certain additional features are available only on the Genomenon Mastermind web user interface, for example, access to more article details, such as color-coded sentence fragments from the full text, supplemental variant matching, visualizations like variant diagrams, filtering, and adding phenotypes. These features would require a separate license through Genomenon.
Please email info@goldenhelix.com to learn more about using Genomenon genomic intelligence in your NGS analyses in VarSeq!
Denice provides technical support and training to Mastermind users at all levels. With a background in germline variant analysis and preimplantation genetics in clinical NGS labs, she turns feedback into function, enabling implementation of Mastermind for a variety of clinical use-cases.
We help provide insights into key genetic drivers of diseases and relevant biomarkers. By working together to understand this data, we enable scientists and researchers to make more informed decisions on programs of interest. To learn more about how we can partner together to find your genomic variant solutions, we invite you to click on the link below.
