Features:

• Support for interpreting SV insertions, including compound heterozygous

• STR enhancements - new pathogenicity filter, allele frequency added to visualization

• New visualization tracks for ClinVar, ClinVar SV and BigWig

• Emedgene Curate supports CNVs

  • Selectable overlap in related cases

  • Export from Analyze to Curate

• Workflow improvements

  • Gene-related disease card improvement

  • Edit interpretation summary

  • Variant page sidecar redesign

• Analysis table enhancement - when variant has conflicting classifications it will be displayed in black

• DRAGEN QC metrics available for download on lab page

• Input sample file errors exposed in the cases page

• Support for ACMG 78 genes in filter

• Admins can add tags in management page

• Header design change to match Illumina software

Enhancement:

• Added organization setting activity log, viewable from dashboard page on all activity including by ILMN support teams on the backend

• Enable lossless compression on PDF reports (a support request)

• API | Ability to get detailed version information via API calls

• Analysis Tools | Preset Filters | Apply gene list on the fly - validate gene symbols with NCBI ID

Bug fixes:

• mtDNA visualization on GRCh37 bug fixes

• Lab Page | Warning when mtDNA were called on wrong reference and no data is presented

• Curate | SNV variants include alt validation

• Curate | Support Indels and mtDNA

• Var Page | Visualization | Instability issues fixed

• Var Page | Remove related disease for genes of unknown significance

• Var Page | Fix broken OMIM links for genes associated with multiple diseases

• Var Page | STR | Allow selection of existing interpretation paragraph

• Analysis Tools | Fix zygosity other family members

• Analyze | Export to Curate | Fix disease export field

Features:

• Support for Dragen 3.10 (support for Graph coming in 5.30)

• Support for SV insertions called from Manta

• Compound heterozygous filter supports SVs (in addition to CNV/SNV/indel)

• Compound heterozygous feature for duos (single parent and proband)

• Annotate cases with Emedgene Curate data

• Support for DRAGEN repeats with ExpansionHunter. For customers using their own pipeline, custom header needs to be added to file.

• Added STR annotation engine for 1K Genomes and gnomAD

• Support for DRAGEN SV caller. For customers using their own pipeline, custom header needs to be added to file.

• Retrieve and annotate with variant interpretation from Emedgene Curate

• Support for ingesting files from ICA2 storage

Enhancements:

• Improvement of de novo variant quality from DRAGEN

• Enhancement | Update revel generation script, change revel file path to fix GRCh38 bugs in revel data

Features

• Feature | New XAI for CNVs and compound heterozygous SNV-CNV variants

• Feature | New and more accurate phenotypic match model, Phenomeld

• Feature | Support for DRAGEN 4.0 with ML for customers running their own DRAGEN and through Emedgene

• Feature | Lab Page | Gene Coverage - Region coverage statistics will now be calculated based on the case’s kit associated BED file

• Feature | Default BED files for coding regions, clinical regions (used for exome) and genomes were updated with latest RefSeq Curated and Gencode versions.

• Feature | Re-including Polyphen annotation, and update to consider most severe value

• Feature | Support for DRAGEN Force Genotyping caller

Bug Fixes

• Bug Fix | Quality metrics for duplications when CN > 3

Features:

• Feature | ACMG SNV | Add note

• Feature | Add report service activity in dashboard

• Feature | Add template name change activity in dashboard

• Feature | Add template upload activity in dashboard

• Feature | Import Gene Interpretation from Curate

• Feature | Enable kit management in organization settings

• Feature | New Phenomeld filter added

• Feature | Presets | Gene list | Search for gene list name

• Feature | Var page | Add Genomenon linkout to clinical significance

• Feature | Display varcaller in varpage

• Feature | Varpage | Enrich related cases

• Feature | Gene list | add NCBI ID to genes in gene list in database

• Feature | Validation of variant retrieval. When system is degraded this will alert users not to work on cases with incomplete variant data.

Enhancement:

• Enhancement | Visualization - add tracks order

• Enhancement | Visualization | Change default locus zoom for BigWig

• Enhancement | Add more ethnicities

Bug fixes:

• Bug Fix | Display chr number for finalized cases in finalize tab

• Bug Fix | Add new case | Reactivate batch mode using HPO IDs

Features

• Pipeline version naming changed to match workbench version.

• Annotation | Ensembl Variant Effect Predictor (VEP) updated to version 108

  • Refseq transcripts updated to version 110

  • The following effect modifications are updated in Filters > Severity > Simple mode

    • New effect types: splice_donor_5th_base_variant, splice_donor_region_variant, splice_polypyrimidine_tract_variant, start_lost, start_retained_variant

    • Modified effect types:

      • nc_transcript_variant ==> non_coding_transcript_variant

      • nmd_transcript_variant ==> NMD_transcript_variant

      • non_coding_exon_variant ==> non_coding_transcript_exon_variant

    • High severity CNV duplication calculation was expanded to include splice_polypyrimidine_tract_variant_, coding_sequence_variant & intron_variant&_feature_elongation in the severity calculation

• Added support for DRAGEN Expansion Hunter's latest default catalog of 60 pathogenic STR loci (including 30 from gnomAD).

• Added support for DRAGEN 4.0 for VCF cases (with disabled Machine Learning pipeline).

• Labs running small panels can define gene list threshold below which case will deliver even without AI Shortlist results.

Bug Fixes

• AI Shortlist | In a previous version, the algorithm for defining compound heterozygous variants was broken for pedigrees with additional samples. There is now support for compound heterozygous variants in any pedigree in the Autosomal Recessive - Compound Heterozygotes Inheritance Filter and Auto Analysis User Filter.

• ACMG Automation | SNVs | Automatic PM5 ACMG tag calculation for SNVs is now more precise.

• Annotation | REVEL | Updated REVEL scores with GRCh38 positions.

• Annotation | mtDNA | APOGEE and MitoTIP mtDNA variant missense prediction scores are displayed again.

• Annotation | ClinGen | Consistent annotation for CNVs classified as Uncertain by ClinGen in GRCh38 cases.

• Variant Page | Format of dbSNP link is fixed.

• Population Statistics | Fixed the issue with CNV population data being displayed incorrectly in some cases.

Features

• User access policy allows organization to select whether invited Illumina support teams will have access to case data and meta data.

• New ordering role with access only to create a case on Emedgene.

Bug Fixes

• Visualization | Fixed bug of visualization failing when a large pedigree contains members with and without samples.

• Visualization | A display issue that affected some CNV/SV variants has been fixed.

• Variant Page | Related Cases | CNV overlap calculation logic has been updated to comply with Curate. The overlap percent is calculated by dividing the number of common base pairs between variants from different cases by the size of the variant under investigation

• Population Statistics | Fixed the issue with CNV population data being displayed incorrectly in some cases.

• If case is resolved and case status is changed, case resolution will not be updated

Features:

• Support for interpreting STRs - annotation with 1K genomes and gnomAD, custom visualization, related cases

• Support for interpreting SV deletions and duplications. ACMG automated classification tool applies to SV del/dups.

• Emedgene Curate supports gene curation - save and view gene interpretations, save preferred transcripts.

• Emedgene Curate - new private networking component for opted in laboratories

• ACMG classification improvements

• In analysis tools disease column, hover to view see all related diseases

• New Filter under Variant Effect, Advanced, Curate - select pathogenicity

• View allele frequency full decimal number

• Var Page | Quality Tab | Add tooltip for quality parameter threshold

• Var Page | Option to import variant interpretation summary from Curate

• Header update - added Illumina logo

Bug fixes:

• Export variant to Curate bug fix

• Organization Settings | Management | Fix broken create group and add users link

• Analysis Tools | Filters | Compound heterozygous filter now supports CNV del/SNV

• Analysis Tools | Filters | ACMG | VUS renamed Uncertain

• Reporting | View reports for past cases even if template has been archived

• API | Fixed error where case type wasn’t saved

For customers validating v34 pipeline, here is a list of updates vs v33.1

• Annotations | Add PrimateAI-3D annotation

• Annotations | Add gnomAD v4 for SNVs

• Variant Data | Make REVEL score available for filtering and export

• Variant Data | Make DRAGEN VCF FILTER field available for filtering

• Case Quality | Update fail & skip logic on case quality and push case quality data to Lab Tab

• Case Quality | Add contamination results from Peddy

• DRAGEN 4.2 | For customers using the Emedgene DRAGEN pipeline, no post-processing of SV and STR VCFs to add headers, as these are included starting in DRAGEN 4.2.

• Emedgene supports case ingestion from VCF for customer variant callers, as defined in customer’s implementation plans. Two new customer callers were added in this version.

• Fixed Issue | Add New Case | Check that BSSH files are fully uploaded before initiating case.

• Fixed Issue | Don’t fail a case if non-mandatory files are not present for some samples.

• Fixed Issue | Export | MiniVCF | VCF format field fixes for broader compatibility with downstream tools

• Fixed Issue | Export | MiniVCF excel file creation will no longer fail for some field types