Illumina launches DRAGEN v4.5, unlocking deep biological signals in complex regions and challenging sample types for rare disease, oncology research

New pangenome representation, default personalization, and machine learning features boost analytical capabilities across applications  

SAN DIEGO , April 16, 2026 /PRNewswire/ -- Illumina Inc. (NASDAQ: ILMN) today announced the launch of DRAGEN™ version 4.5 software (v4.5), one of the most substantial expansions of the software's capabilities to date. As genomic researchers contend with complex regions of the genome, degraded samples, and multiomic data types, DRAGEN v4.5 delivers new ways to reduce noise, improve accuracy, and extract biological signals, giving researchers greater discovery power to fuel findings in rare disease and oncology.

This release enhances DRAGEN's strong germline foundation with expanded pangenome representation and personalization, further improving variant calling accuracy and performance in challenging genomic regions. v4.5 provides analytical support for Illumina TruPath™ Genome, resolving challenging-to-map regions of the genome.

"These advances expand the scope of biological questions researchers can address across germline, oncology, and multiomic applications—while maintaining the speed, scale, and operational consistency expected from DRAGEN," said Rami Mehio, senior vice president and general manager of BioInsight at Illumina. "BioInsight is all about making bioinformatics accessible, reliable, and scalable, whether you are a researcher seeking insights into rare disease or a pharma partner pursuing drug discovery from datasets."

DRAGEN v4.5 key updates

• Significantly expands multiomic analysis, with structural variant calling and improved small variant accuracy for Illumina's 5-base solution, enabling more integrated genetic and epigenetic insight
• Introduces machine-learning-driven somatic analysis and expands oncology insights with new capabilities like oncovirus detection
• Strengthens the scalable multiomic pipelines that support ambitious projects, like the recently announced Billion Cell Atlas

David Spencer, a researcher at Washington University School of Medicine in St. Louis, applied v4.5 to his trial of Illumina's 5-base assay on acute myeloid leukemia, or AML, samples. Genetic mutations detected at diagnosis are important predictors of clinical outcomes in AML. Persistent mutations in remission are also predictive of relapse. Spencer is exploring whether epigenetic changes can be used as biomarkers to further improve predictions of relapse. His team found that 5-base provided highly accurate methylation information and detected abnormal epigenetic patterns in samples with clonal disease in remission, highlighting the potential of integrated genetic and epigenetic analysis to improve disease characterization and monitoring.

"Illumina 5-base and DRAGEN v4.5 combine variant detection and methylation with added structural-variant calling capabilities, expanding the set of genomic changes that can be explored as potential biomarkers in AML samples," said Spencer.

Personalization, machine learning are among new features of DRAGEN v4.5

Advances in v4.5 enhance secondary analysis in genomic and multiomic workflows.  

• New algorithms support Illumina TruPath™ Genome: v4.5 introduces analytical support for TruPath, leveraging algorithmic advances to resolve 15 highly homologous, medically-relevant genes for rare disease research.
• Personalization improves germline variant calling: Personalization by default further reduces germline small variant errors, delivering approximately a 20% reduction in false positives and false negatives compared to v4.4.
• Pangenome better reflects global genomic diversity and reduces ancestry-related bias: The addition of Middle Eastern reference genomes expands the DRAGEN pangenome to better represent global population diversity, improving mapping and variant calling across underrepresented ancestries. In parallel, targeted improvements to the SMN1 variant caller enable detection of silent carriers, addressing a known source of underdiagnosis in certain populations.
• Machine learning expands Illumina's 5-base solution: The release introduces structural variant calling for both germline and somatic applications of 5-base, alongside improved germline small variant accuracy and personalization enabled by data specificity and machine learning. Illumina Connected Annotation further supports these analyses by highlighting genomic regions of interest informed by methylation data, simplifying interpretation of complex multiomic datasets.

Oncology features bring bioinformatics power to complex cancer questions

Formalin fixed paraffin embedded (FFPE) samples present substantial technical noise that can make it difficult to identify relevant variants. v4.5's machine-learning-driven somatic small variant calling reduces FFPE-associated false positives by over 90% for single nucleotide variants and over 87% for indels—improving sensitivity without increasing runtime or computational burden. Opt-in machine learning separates true variants and background artifacts, improving sensitivity at low tumor purity. This enables more reliable detection of biologically relevant variants in challenging samples.

Additionally, v4.5 debuts robust oncovirus detection. Certain viruses, such as human papillomavirus (HPV), can drive cancer development by disrupting normal cellular control mechanisms, sometimes through integration of viral DNA into the host genome. In internal tests, v4.5 detected 100% of expected oncoviruses and identified 18 additional oncoviruses, showcasing the software's sensitivity for high-risk strains of HPV and Epstein-Barr Virus. Researchers can use this information to develop new tests and targets for oncovirus-driven cancers.

The software is available via on-premises servers and in the cloud. Register today for our April 30 technical webinar to see DRAGEN v4.5 in action and read the technical blog to learn more.

Use of forward-looking statements

This release may contain forward-looking statements that involve risks and uncertainties. Among the important factors to which our business is subject that could cause actual results to differ materially from those in any forward-looking statements are: (i) challenges inherent in developing, manufacturing, and launching new products and services; (ii) customer uptake of, and satisfaction with, new products and services; and (iii) legislative, regulatory and economic developments, together with other factors detailed in our filings with the Securities and Exchange Commission, including our most recent filings on Forms 10-K and 10-Q, or in information disclosed in public conference calls, the date and time of which are released beforehand. We undertake no obligation, and do not intend, to update these forward-looking statements, to review or confirm analysts' expectations, or to provide interim reports or updates on the progress of the current quarter.

About Illumina
Illumina is improving human health by unlocking the power of the genome. Our focus on innovation has established us as a global leader in DNA sequencing and array-based technologies, serving customers in the research, clinical, and applied markets. Our products are used for applications in the life sciences, oncology, reproductive health, agriculture, and other emerging segments. To learn more, visit illumina.com and connect with us on X, Facebook, LinkedIn, Instagram, TikTok, and YouTube.

Contacts

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SOURCE Illumina, Inc.