SeqOne Platform Update - v1.44

SeqOne Platform - v1.44

Dear SeqOne Users,

Welcome to version 1.44 of the SeqOne Platform! We're excited to introduce powerful new AI capabilities, major analytical upgrades, and a host of user experience enhancements.

This release is headlined by the pre-access launch of "DiagAI Autofill", an intelligent assistant designed to accelerate variant interpretation. We're also rolling out significant improvements to our core pipelines, including SomaRNA 3.0 with full hg38 support, and a new rescue caller to improve detection in critical hereditary cancer genes.

To streamline your daily workflow, you'll also discover visual tags for complex genomic regions, and a fresh, cohesive look for all your worksets icons.

🤖✨ DiagAI can now Auto-Fill Your Comments!

We are happy to present our new feature: automatically generate your interpretation comments with DiagAI! When interpreting variants, simply click the "AutoFill with DiagAI" button to instantly generate a draft comment tailored to the displayed pathology.

This intelligent assistant exclusively uses existing information, including SeqOne variant annotations (like pathogenicity scores), relevant disease information from OMIM (prioritizing matches with any HPO terms you've entered), and concise summaries of the latest research from LitVar, ensuring comments are data-driven and grounded. You always remain in control, with language settings available and the ability to easily cancel suggestions and revert to your initial comment.

Curious to see how this new feature accelerates variant interpretation? Explore the methods in our poster, freshly presented at ESHG 2025!

This feature is currently in pre-access; please contact us to arrange a personalized demo with our experts and test drive this exciting new capability!

🏷️ Complex Regions: New Visual Tags for At-a-Glance Variant Context

We are happy to release a feature that brings deeper context directly into your analysis workflow. The variant page has been enhanced with new visual tags that instantly flag when a variant falls within a challenging region. You’ll find these clear, informative tags—such as AAA for homopolymers, DUP for segmental duplications, and PAR for pseudo-autosomal regions—in both the HGVS column in the Variant Table, and the header of the Variant Details page.

This user-friendly update ensures you can see and act on the data from our improved annotation, giving you immediate insight for a more comprehensive review.

🎨 A Fresh Look for Your Worksets

We are very happy this month to introduce a visual refresh for all workset logos across the platform! In this update, existing icons will be replaced with new, distinctive pictures. This change brings the workset visuals in line with our recent platform-wide design updates, ensuring a more unified and cohesive interface.

Here’s a first look at some of the new logos!

🎯 Enhanced Variant Detection in Lynch Syndrome and Critical Hereditary Cancer Genes

We're targeting difficult-to-call variants with a powerful new update to our GermlineVar and GermVar pipelines. To boost detection in challenging homopolymer regions, we've introduced a specialized rescue caller that intelligently re-analyzes base counts to find and report variants that standard haplotype variant callers might otherwise miss.

You will see immediate improvements in sensitivity for key hereditary cancer genes in GermlineVar (versions 2 and above) and GermVar (v3 and above), including:

• Lynch syndrome: MLH1, MSH2, MSH6, PMS2, EPCAM
• Other key genes: APC, BRCA1, BRCA2

Good news for somatic analysis—this feature is planned for those worksets next. Stay tuned!

🚀 Meet SomaRNA 3.0: A Leap Forward for Your RNA Analysis

SomaRNA 3.0 is here, and it’s packed with features you’ve been asking for. First and foremost, you can now run all your analyses on the hg38 reference genome.

This major version also focuses on performance and deeper insights:

• Enhanced Performance & Stability: We've upgraded the Arriba fusion caller and fixed previously reported crashes, making your analyses faster and more reliable.
• Increased Detection Sensitivity: SomaRNA now reports fusions called with low confidence, with the confidence level clearly displayed so you can explore more potential events without sacrificing clarity.
• Flexible UMI Handling: The "Disable UMI" mode gives you more control by letting you skip the deduplication and consensus step when needed for your specific workflow.

Continuous Improvements

We have made several enhancements to improve your daily workflow:

• Enhanced JSON Export and Selection Workflow: We have enhanced the JSON export functionality presented in last month’s release. Note that this feature is still brand-new, and will continue evolving and improving over the next releases! Here are this month’s additions:

• • The "Summary" page has been renamed to Dashboard, and selections made there are now fully synchronized with the Selection Drawer for perfect consistency (SomaCGP, SomaLBx, and SomaVar Tertiary).
  • You can now generate a report or a JSON export directly from the Selection Drawer, which features a new, more intuitive layout.
  • This improved workflow is retro-compatible, and the JSON export from the VKB annotated variants in the Selection drawer will now be available for all Somatic and Germline analyses that have a VKB option: SNVs in SomaVar, SomaVar LF, SomaHemato, SomaRNA, GermlineVar, Germline Family, GermVar, GermVar Family. Stay tuned in the next releases for increased export capabilities, with the progressive addition of Dashboards to these worksets too! 

• Expanded hg38 Compatibility:

• • We've broadened our support for the hg38 reference genome. SomaMSI is now fully hg38-compatible.
  • Furthermore, to create a more seamless workflow, you can now launch a SomaCNVcapture or SomaMSI analysis in hg38 if you have a matching SomaVar LF or SomaHemato analysis.

• Clearer Transmission Mode: In the variant table, the Transmission Mode is now highlighted with a distinct color when it is not supported by OMIM, making these cases easier to identify at a glance.

• Expanded Language Support: HRD and Clinical reports can now be generated in Italian. 

• Improved Data Export: To ensure data integrity, HGVSp nomenclature containing parentheses is now correctly formatted in all data exports.

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

• Fixed an issue where Alumei (our Alu-insertion caller) would crash on duplicate insertions with same breakpoints.
• Fixed an issue with GermVar Family (versions 3+ only, GermlineVar unaffected) where variant quality was not properly handled, affecting DiagAI scoring and ranking.
• Fixed an issue in the TSV export of the Variant Table, where the HGVSp column would have unrequested “%” characters (ex: “%3D” character instead of a “=”).

The Instructions for Use have also been updated to include this month's improvements. As usual, you can view or download them in your preferred language from the “About” section in the user settings.

The sections below have been updated:

• 7.1 Login
• 11.1.1 Choosing the analysis workset
• 11.1.2 Choosing the UMI processing mode
• 12.1.4 IGHV mutational status report
• 13.1.2 Overview of analysis results in the Dashboard tab
• 13.1.4 Small variants
• 13.1.5.1 CNV in gene panels
• 13.1.5.2 CNV in SomaCGP and SomaLBx analysis
• 13.1.11 HRD/HRP status