Connected Insights v5.3: Advancing Precision with AI-Driven Accuracy and Tailored Reporting

The landscape of precision oncology is moving faster than ever. At Illumina, we strive to ensure our tools keep pace with the researchers who use them. Illumina Connected Insights version 5.3 represents the next evolution of our flagship oncology interpretation platform. 

Building on the foundation of our v5.2 release which introduced broad compatibility for non-Illumina datasets and faster times to report, version 5.3 focuses on deeper biological context and operational efficiency.

Release Highlights

• Oncogenicity Prediction Improvements: 96% accuracy in variant oncogenicity classification, leveraging latest refinements in Illumina’s proprietary AI algorithms
• Report Customization: Greater flexibility to tailor research reports to your lab’s specific needs without requiring manual data re-entry
• Advanced Variant Interpretation: Deeper insights through co-occurring biomarker evidence, in-frame fusion identification, and geographic-based clinical trial information 

Latest enhancements included in v5.3 are driven by our commitment to helping labs navigate the path from raw sequencing data to a finalized research report with greater ease and scientific clarity. Let’s take a closer look at what’s included in the latest version of Connected Insights. 

Refined AI for superior oncogenicity prediction

One of the most significant challenges in oncology research is the burden of VUS - the overwhelming number of variants of uncertain significance, lacking literature or evidence to properly classify actionability. Connected Insights offers automated, guidelines-based oncogenicity classification of variants, integrating proprietary Illumina PrimateAI-3D and SpliceAI algorithms to empower users to achieve greater variant classification accuracy and confidence in their insights. In version 5.3, we have further optimized our automated oncogenicity prediction functionality, reaching 96% accuracy. 

In a benchmark study using a 94-variant truth set based on ClinGen/CGC/VICC guidelines, Illumina Connected Insights demonstrated exceptional concordance, correctly predicting oncogenicity for 90 of the 94 variants. This high level of accuracy represents a significant advancement over existing industry benchmarks, which typically hover around 80%*. 

These refinements offer:

• Increased accuracy: Higher precision in identifying causal mutations versus benign variants
• Reduced manual review: By sharpening the prediction scores, v5.3 helps researchers automatically prioritize the most impactful variants and review reduced variant lists significantly faster
• Confidence in Insights: Advanced AI algorithms produced by Illumina BioInsight (Splice AI, PrimateAI-3D) ensures that rare or novel variants are interpreted with the latest evidence-backed genomic intelligence

*Illumina internal study, Jan 2026. 

Personalized reporting at scale

We understand that every lab has a unique research workflow and specific reporting requirements. Version 5.3 introduces advanced report customization, giving users full control over their final output. Reports can now be easily customized directly through the user interface, allowing users to select and organize report sections, adjust content, and tailor the presentation to specific needs.

Elevating interpretation with new biological context

The biological landscape of a tumor is rarely defined by a single mutation. To capture this complexity, version 5.3 enhances variant interpretation through the ability to create and view co-occurring biomarker evidence. This feature allows researchers to identify and consider the interplay between multiple biomarkers, providing a more holistic understanding of the tumor profile and potential therapy resistance.

Connected Insights v5.3 is bringing new interpretation capabilities for fusions, now automatically identifying fusions as inframe or frameshift to enable easy filtration based on fusion type for focused analysis.

Last but certainly not least, we are introducing reporting of location-based trial results, allowing users to automatically prioritize clinical trials based on the subject’s geographic location. By configuring results based on a subject’s location, users can significantly reduce their time spent manually vetting the feasibility of trial enrollment.

Learn More

We are proud to continue evolving alongside the oncology community. By prioritizing usability and precision, this latest update to Connected Insights empowers you to go further in your precision oncology research. To learn more about Connected Insights and our latest innovations, please access the following resources: 

• Visit the Connected Insights webpage to learn more about our technology
• Request a free trial of Connected Insights to gain access to latest v5.3 features
• Explore the Release Notes for a full list of technical updates and compatibility improvements

For Research Use Only. Not for use in diagnostic procedures.

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