New in emedgene 2.29 (August 25 2022)

1. New Variant Types Supported

   1. SV Insertions

   2. STR Improvements

2. New Visualization Tracks

   1. Curated Data Tracks

   2. BigWig Track for CNV Visualization

   3. Additional

3. Emedgene Curate + CNVs

4. Additional new features

   1. Gene-related disease card update

   2. Edit interpretation summary

   3. Variant page sidecar redesign

   4. Enhancement to Analysis Table

   5. Lab Page Enhancement

   6. ACMG 78

   7. Expose input file errors

New Variant Types Supported

SV Insertions

Emedgene now supports calling and interpretation of SV insertions called by the DRAGEN Manta SV caller.

Calling:

The DRAGEN Manta SV caller detects simple insertion/deletion events , and detects both fully-assembled and partially-assembled (inferred) insertions. Minimum size of SV insertion is 50bp. Indels smaller than 50bp are called by the regular SNV caller and annotated as SNV.

Known caller limitations:

• The maximum fully-assembled insertion size should correspond to approximately twice the read-pair fragment size, but note that power to fully assemble the insertion should fall off to impractical levels before this size.

• Note that Manta does detect and report very large insertions when the breakend signature of such an event is found, even though the inserted sequence cannot be fully assembled.

• In the case of partial assembled insertions, the size of the variant displayed does not reflect its true size.

Note that for customers bringing their own DRAGEN pipeline into Emedgene, specific VCF headers in the SV file need to be added before sample ingestion. Contact support for more information.

Annotation:

SV insertions are annotated with gnomAD SV and ClinVar SV data, for population frequencies and known pathogenicity. Insertion annotation is performed on the basis of the insertion start position; the sequencing content is not considered.

Interpretation:

Variant page and analysis tools have been adapted to support SV insertions.

• Variant type will be clearly marked in the header

• New filters added for filtering SV insertions, quality filtering for both length and bin count can be applied (see remark above regarding the INS size).

STR Improvements

• New pathogenicity filter

• Allele frequency is now viewable in the proprietary STR visualization

Summary Table of Variant Types Supported by Test Type and Version

Variant Type	WGS	WES	Panel	Emedgene DRAGEN	Bring your own DRAGEN	Platform Version
SNV	Yes	Yes	Yes	All	All	All
Indel	Yes	Yes	Yes	All	All	All
CNV	Yes	Yes	Yes	All Need PON - exome/panel	5.24+ Need PON - exome/panel	2.22+
mtDNA	Yes	Yes	Yes	All	5.26+	2.25+
SV del/dup	Yes	Yes	Yes	Yes	5.28+ Needs adjustment	2.28+
SV insertion	Yes	Yes	Yes	Yes	5.29+ Needs adjustment	2.29
STR	Yes	No	No	Yes	5.29+ Needs adjustment	2.28+

New Visualization Tracks

Curated Data Tracks

You can now add ClinVar and ClinVar SV tracks to the in-platform visualization. Pathogenicity corresponds to the ClinVar color scheme, with black denoting a conflict.

BigWig Track for CNV Visualization

BigWig visualization is now available for WGS cases, specifically the tangent normalized signal points view. This visualization helps interpret CNVs by clearly showing the bins and breakpoints.

For customers bringing their own DRAGEN output, a VCF and BigWig data can be shared via the API and batch upload tool.

These new tracks are available in both simple and advanced modes, allowing you to configure the visualization tab as needed.

Additional

A known mtDNA visualization discrepancy on GRCh37 was fixed in this version.

As always, we support synchronization with IGV desktop, and all settings in the platform can be mirrored to the IGV desktop environment which continuously displays the current selected variant data.

Emedgene Curate + CNVs

CNVs are now supported in Emedgene Curate! Including streamlined annotation and analysis flow integration, all the way through to auto-populating report template fields.

• Add a CNV variant directly to Emedgene Curate, or import during your case analysis;

• Search for a CNV by range, type or gene;

• Variant header, info card and gene’s related disease components have been adapted for CNVs;

• Select a disease for a curated CNV variant;

• Explore the related cases table - filter by % annotation overlap.

• In your Curate navigation, you will notice a new column denoting Variant Type. For labs with enabled private networks, the icon will denote pathogenicity by color, with a hover showing more details.

Additionally:

• Once you have curated a CNV variant, all future cases including in your private network if enabled, will be annotated with your data.

• Once a variant is reviewed, curated data can be imported and used to automatically populate a report template field.

Additional new features

Gene-related disease card update

The gene-related disease has always shown a numeric summary of phenotypic match, for patient phenotypes found in the disease out of all patient phenotypes.

This card now shows a numerical match between patient phenotypes and disease phenotypes. The full list of disease phenotypes is displayed, with the phenotypic match strength for each. A link to the full list of patient phenotypes will open the side car for an easy view and comparison.*

Edit interpretation summary

Edit the interpretation summary at the top of the page, in addition to the edit capability in the evidence tab.*

*Note that both of these new capabilities are only available for variants tagged by the AI Shortlist or users as most likely or candidates.

Variant page sidecar redesign

The variant page sidecar has been redesigned.

• Includes a default view:

  • Sample names of proband and family members.

  • Proband phenotypes, and family if available

• Allows you to configure your desktop IGV and Alamut connections, including the new Alamut API.

• The sidecar can be collapsed and expanded, and does not cover active window

Enhancement to Analysis Table

In the analysis tools, the known variant column colors had previously ignored VUS (variants of unknown significance) classifications if appearing in conjunction with P/LP or B/LB.

This has now been updated and if a variant has both P/LP and VUS classifications or B/LB and VUS classification, the appropriate mixed colors will appear.

If a variant has conflicting classifications it will appear in black.

Lab Page Enhancement

For labs using the Emedgene DRAGEN pipeline, QC metrics are now available for download.

ACMG 78

Updated filters to support full ACMG 78 gene list.

This update follows the latest recommendation from ACMG for reporting secondary findings: https://www.acmg.net/PDFLibrary/Secondary-Findings-v3.1.pdf.

Expose input file errors

The majority of case pipeline failures are due to errors in customer input files. We now expose explicit and detailed input file errors on the cases page.