Version 96 Updates

We are happy to introduce several enhancements and new features in our latest update:

Franklin’s repeat expansion annotation catalog has been updated to support additional repeat expansions called by the short-read caller ExpansionHunter. As a part of this update, some previously supported repeat expansions will now be annotated using more recent curated publications and clinical evidence and will have a suggested classification based on updated classification thresholds.
Note: This update only affects repeat expansion annotation in new or re-analyzed cases, it does not affect calling. For more information on repeat expansion variants in Franklin, please visit the following Help Center article.

Germline cases now support VCFs emitted by PacBio long-read sequencing callers Sawfish (SV), TRGT (repeat expansions), and Mitorsaw (mitochondrial). These VCFs can be used for case creation alone or in conjunction with VCFs from additional callers, including other long-read callers such as Sniffles2. Repeat expansions from TRGT are annotated using Franklin’s repeat expansion annotation catalog, which now supports variants emitted by this caller; for more information on repeat expansion variants in Franklin, please visit the following Help Center article. To configure a long-read assay for your organization, please contact our support team ([email protected]).

In germline cases, the Additional Information section of the Workbench can now include the PMS2 biomarker, allowing you to view and report copy number abnormalities for PMS2 homologous region, i.e. exons 11–15:
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Using a dedicated Rainbow homology model, Franklin estimates the total copy number (CN) across PMS2 and PMS2CL pseudogene, and additionally splits it into separate PMS2 and PMS2CL values based on paralogous sequence variant (PSV) evidence. The PMS2 biomarker tile displays an overall status, and expands to a per-exon table showing the determined total CN, total CN confidence, individual PMS2/PMS2CL CN values, and supporting PSVs, with abnormal exons highlighted for quick review. Biomarkers can be added to or removed from the report, with the level of detail configurable for your organization. For more information on the PMS2 biomarker, please visit the following help center article.

The confidence widget can now display confidence information produced by targeted kit region Rainbow models. This information is available at the CNV level from the variant popup, as well as at the gene level from the Coverage Report (from “Gene confidence view”, available on the gene tile). The added support allows to view confidence information per kit region, displaying not only coding exons but also non-coding exons and non-exonic regions.

The genes track includes distinct visual representations and tooltips for coding exons, non-coding exons, exons split across kit regions, kit regions spanning multiple exons, and non-exonic regions. It also includes accurate information for coding and non-coding UTRs:

In the Predicted Copy Number track, regions with failed predictions are plotted on the baseline with a value of N/A and connected using a dashed line to clearly indicate this result:

Note: Regions outside the kit are not displayed by the widget (including off-target exons in genes partially covered by the kit). To enable the confidence widget in a kit region assay, please contact our support team ([email protected]).

CMA cases can now be created from VIA (NxClinical) v7.2 text file output, as was previously supported only for NxClinical v6.1. Cases can be created using sample sheet or the implicit (shell case) API.

Fusion variants search is now available on Franklin’s Search. Fusion search is possible when selecting the “Somatic” variant type:

Examples of the supported input format are provided in the “Fusion” popup. The search result is a fusion variant page, similar to the search page of other variant types.

In tumor (somatic) cases, fusion variant breakpoint location and region display have been improved. In fusion variants previously showing N/A for the 3’ gene exon/intron number, a value will now be displayed on the tile. Additionally, we improved the consistency of breakpoint locations and exon/intron number display across the variant tile, popup header, and fusion viewer. Finally, the fusion viewer now loads for more variants, and the breakpoint connector has been refined to visualize the fusion more accurately.

In Franklin API V1, the Create Case Explicit API request can now include tumor purity when creating tumor (somatic) cases. Similar to when specifying tumor purity in a sample sheet, the expected value is a number, e.g. “48.5” for a tumor purity of 48.5%, and the created case will display this value in Sample Details. For more information on Franklin API, please visit the Franklin API documentation (https://api-docs.genoox.com/).

Resolved an issue where the HBA biomarker’s “Not tested” status was not displayed when the biomarker was configured in the assay but was originally absent from the Dragen targeted caller output used as its input.