SeqOne Platform Update - v1.42

SeqOne Platform - v1.42

Dear SeqOne users,

We’re excited to share a range of new features and enhancements in this month’s release, designed to improve your workflow and provide deeper insights into your data. From the ability to combine multiple filter presets using OR operations, to enhanced inheritance pattern filtering for germline analysis, these updates bring new flexibility and precision to your work. We’ve also made significant strides in somatic analysis with the introduction of SomaHemato for clonality assessment in CLL, SomaLBx for enhanced Liquid Biopsy analysis, and expanded support for VCF files in SomaVar Tertiary. 

Read on to explore how these updates will help you unlock more value from your genomic data!

🧩 Combine filter presets: the OR option is here!

We're especially excited to announce a significant enhancement to our filtering system: Preset Combos. This new feature allows users to combine multiple filter presets using OR operations—for example, you can now display variants that match either a quality-linked filtering profile or ClinVar criteria; or combine manually curated criteria while retaining top AI variants.

The new "Combo" tab in the filter drawer makes creating combinations simple—just select two or more saved presets to display variants matching any of your chosen criteria.

The "Basic" filter tab remains unchanged in functionality but features a slight visual refresh to match the new "Combo" tab design. These combos work seamlessly with both private and public profiles (combos featuring a private profile will be private), and automatically update whenever their constituent presets are modified.

This enhancement provides greater workflow flexibility and reduces false negatives by enabling simultaneous application of multiple control presets. We'd love to hear how it improves your workflows!

🧮 Enhanced Variant Effects Filter: New Intuitive Category System

Still on the filtering topic, we are also introducing improvements to our variant effects filter box. The new grouping system organizes the numerous predicted effects into intuitive categories like "Loss of Function", "Coding", "Splicing region", and more. Users can now seamlessly add or remove entire categories with a single click, while maintaining complete flexibility to select specific effects. All effect categories remain visible, regardless of whether they match any variants. 

This streamlined filtering process improves workflow efficiency while preserving all existing filter presets.

👩‍👩‍👧‍👧 Improved compound heterozygous and other Transmission Pattern Filters!

We're pleased to share a significant update to our germline variant filtering capabilities, with improved transmission pattern filters for both family and solo analyses. The options include compound heterozygous variants (either suspected or, in trio analyses, verified), recessive homozygous, and de novo variants—all easily accessible through the filter menu presets. In the variant viewer's "transmission" column, we've added color-coded pictograms showing the matching pattern(s). 

Powered by DiagAI's inheritance compatibility scoring, this update simplifies variant interpretation and removes previous filtering limitations. Only variants with a suspected pathogenicity based on UP2 score are retrieved, thus improving the accuracy of those filters.

🧬 GermVar 3.3: CNV & Family analysis for WGS

Building on last month’s release, we are also sharing significant improvements to our Whole Genome Analysis capabilities in GermVar 3.3. This update introduces whole-genome CNV calling, which is now seamlessly integrated into the GermVar WGS workflow. Additionally, we've added comprehensive support for Family analyses, enabling more sophisticated genetic investigations - like our other Germline worksets, GermVar WGS supports duos, trios, and up to 7 family members.

GermVar 3.3 now also includes our AluMEI tool for Alu-insertion calling, with all of its exciting updates described below!

These enhancements represent our ongoing commitment to providing cutting-edge genomic analysis tools. More exciting features are in development - stay tuned for future updates!

🔬 New insights into Alu insertions with exciting AluMEI updates

We are excited to introduce several updates to AluMEI, our in-house caller for ALU insertions, making your ALU interpretation workflow more powerful and easier to use.

• Allelic Frequency (VAF) and Quality are now available for AluMEI: While continuing to use our soft-clip approach for Alu insertion calling, we now also utilize reads to compute coverage and matching Allelic Frequency for each detected event. All measurements are recalibrated for precise estimates. A new QUAL score is calculated from reads containing the Alu insertion and extrapolated across coverage.
• AluMEI annotation now includes non-coding sequences! Previously, non-exonic regions were excluded during annotation. Now, we properly annotate and retain intronic and UTR regions, ensuring you don't miss important splice regions. While this update may only add a few variants, it represents a significant improvement in functionality.

🩸Assess clonality in CLL with our brand-new SomaHemato workset!

We're thrilled to introduce SomaHemato, an exciting expansion of our Somatic analysis suite that brings powerful, specialized hematological analysis tools.

This innovative workset features an IGHV mutational status report for clonality assessment in CLL (Chronic Lymphocytic Leukemia), and comes packed with our already available hematology-specific modules for FLT3-ITDs detection, KMT2A-PTD, gene fusions, and TP53 IARC annotation. The solution is fully compatible with Illumina 2x150bp and 2x250bp sequencing length, powered by our sophisticated algorithms for optimal region reconstruction even from short reads!

Please reach out to us if you are interested in being an early adopter!

🚀 Unlock the power of our tertiary analysis for somatic VCFs

We are excited to announce the release of SomaVar Tertiary, featuring expanded support for variant data from Thermo Fisher, AmoyDx, and Pillar Bioscience platforms.

This workset enables processing of VCF files for combinations of:

• SNV (Single Nucleotide Variants)
• CNV (Copy Number Variations)
• Gene Fusions

Make the most of your VCF files with the full power of our comprehensive suite of visualization and interpretation tools - including variant viewer, DNA fusion viewer, CNV viewer with their functionalities for annotation, sorting, filtering, and intuitive data exploration!

🌟 Join Our SomaLBx Early Access Program!

Using Agilent panels for liquid biopsy? Need a powerful analytics solution? Be among the first to test-drive our cutting-edge pipeline, share your feedback, and shape the future of liquid biopsy analysis. 

This month, be among the first to test-drive an early release of SomaLBx, a powerful alternative to SomaVar LF that promises enhanced performance for liquid biopsy analysis. Powered by Sentieon, this new solution will offer accelerated secondary analysis, improved SNV and CNV detection as well as comprehensive fusion calling.

The initial release is fully compatible with AVIDA Expanded and Discovery panels, but more to come - stay tuned! Spots are limited—contact your local representative to set up the test.

We have made several enhancements to improve your daily workflow:

• 🔗 Enhanced aCGH Analysis Integration: Links to NGS in tertiary aCGH analysis are now properly maintained and don’t have to be re-selected every time the analysis is opened.
• 🧬 Improved Mitochondrial Phenotypic Analysis: Added mitochondrial variants to Phenogenius, enhancing ranking and shortlisting capabilities.
• 📝 Enhanced HPO Filter Usability: the recently released HPO filter included viewable gene lists and a TSV export with IDs and scores. It now also has a quick access button to copy-paste comma-separated gene lists.
• 📊 Refined CNVCapture status rules: Updated logic to flag genes with CNV even if some exons failed the calling, for a more comprehensive display of the results.
• 🔐 Strengthened Analysis Security: Improved locked analysis protection - the VKB comments and the user assignments can only be modified after unlocking the analysis.
• 🖥️ Streamlined Column Management in the Variant Viewer: Removed redundant columns which had been merged with other columns a while ago ("impact" and "HGVSp"), and introduced group management features, allowing toggle control for entire groups like GnomAD. The export format of the variant table is unchanged.

We have addressed several issues to improve platform stability and performance:

• Fixed a bug where the “properly covered” genes could not be displayed in GeneCov. You can now visualize all of your genes, and integrate them to your clinical reports!
• Fixed a bug where the wrong VAF could sometimes be displayed in the “occurrences” tab for GermlineVar Family analyses.
• Fixed a bug where, after reprocessing an analysis with new HPO, sometimes Phenogenius and associated HPO scoring wrongly appeared as disabled in the Variant Details and DiagAI explainability tab.
• Fixed a visual glitch where the column headers of the Variant Viewer would sometimes be misaligned when displaying prediction scores.
• Fixed a bug that prevented clinical reports from being generated for some GermVar Tertiary analyses.

Please note that our databases and resources have been updated to their latest versions to ensure you have access to the most current information for your analyses.

• OMIM - version March 05 2025
• ClinVar - version March 2025
• JaxCKB - version March 2025

The manual sections have been reorganized as Instructions for Use to better align with the workflow of SeqOne platform users. The manual has also been updated to include this month's improvements. As usual, you can view or download the manual in your preferred language from the “About” section in the user settings.

The following sections have been added or updated:

• • Intended use of the platform
  • Admin management - interface presentation
  • Managing the user settings - definitions
  • Description of the operational steps
  • Secondary analysis files
  • Choosing the analysis workset 
  • Small Variants
  • CNV in Exomes and Genomes
  • Databases