TruPath Genome solution

Sequencing, reimagined

The most accurate genome with expanded insights and unmatched simplicity

Introducing TruPath Genome

Illumina TruPath Genome transforms whole-genome sequencing (WGS) by combining the accuracy and accessibility of short-read sequencing with long-range insights traditionally limited to long-read platforms. TruPath Genome delivers an ultra-simple workflow, unlocking challenging genomic regions, structural variants, and phased variant calls across the human genome.

Key features and benefits

Accuracy

TruPath Genome represents a step‑change in genome accuracy, not just incremental improvement. TruPath Genome raises the accuracy bar for whole‑genome sequencing across all genomic variants.1

Simplicity

TruPath Genome vastly simplifies WGS implementation and reduces hands-on time to ~10 minutes. Trusted Illumina transposase chemistry eliminates traditional library prep steps.

Expanded insights

TruPath Genome provides long-range genomic insights with ultra-long phasing and structural variant (SV) visualization. The solution reveals haplotype-resolved genomes and complex rearrangements.

Scalability

TruPath Genome provides a scalable, comprehensive genome from a few to thousands of samples per year. TruPath Genome delivers up to four times more genomes per run and cuts end‑to‑end turnaround time nearly in half compared to current long‑read approaches.2

Product data highlightsa-b

Video

The path to genome innovation

Steve Barnard, PhD, CTO and Head of Research & Product Development at Illumina, introduces TruPath Genome at AGBT 2026 and discusses how this transformative solution delivers an ultra-simple workflow—with ~10 minutes hands-on time—unlocking challenging genomic regions, structural variants, and phased variant calls across the human genome.

Workflow highlights

Up to 16 genomes per run

~10 min hands-on time

>4,000 genomes per year (>30× coverage)

A faster, more scalable solution for long-range genomic insights: Comparable workflow for clinical translational research assumes no flow cell reuse and >30x coverage. 
    Calculations based on internal estimates. Based on “Clinical long-read genome sequencing for rare disease diagnostics”, de Bitter et al​.

A faster, more scalable solution for long-range genomic insightsc

Compared to current long‑read approaches, TruPath Genome delivers up to four times more genomes per run and cuts end‑to‑end turnaround time nearly in half.

By nearly eliminating hands-on sample prep, accelerating sequencing, and dramatically reducing turnaround time without compromising data quality, TruPath Genome enables generation of up to 4,000 genomes per year (with greater than 30× coverage) on a single NovaSeq X Plus System. ​

TruPath Genome sequencing workflow

Powered by proximity mapped read technology, TruPath Genome enables human germline whole-genome sequencing with improved coverage, higher accuracy variant detection, and unprecedented simplicity. On-flow-cell library prep eliminates standard library prep prior to sequencing.

Step 1

Prep

Female scientist inserting a 8 flow cell lane library tube strip into into sequencing reagent cartridge on lab bench with other consumables, single pipettes, and library tubes in the foreground.

Step 2

Sequence​

Close up image of a scientist loading a second 25B flow cell cartridge into the NovaSeq X drawer.

Step 3

Analyze​

Two female scientists are working together, looking down at a monitor on a laptop in a lab setting.

How TruPath Genome works

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Illumina TruPath Genome transforms whole-genome sequencing (WGS) by combining the accuracy and accessibility of short-read sequencing with long-range insights traditionally limited to long-read platforms. TruPath Genome delivers an ultra-simple workflow, unlocking challenging genomic regions, structural variants, and phased variant calls across the human genome.

Hear from experts

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Mapping the future of WGS

Joseph Devaney, PhD, Director of Laboratory Innovation Team at GeneDx, compares data and shares his perspectives on the potential impact of proximity mapped read (formerly constellation) technology.

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Perspective: Experience with TruPath Genome

Marcel Nelen, PhD, Head of Genome Diagnostics at UMC Utrecht, discusses the types of studies that may benefit from mapped read technology.

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Deeper insight into complex genomic regions

Steve Barnard PhD, CTO and Head of Research & Product Development at Illumina, outlines the research challenges Illumina TruPath Genome is designed to address.

Speak to a specialist

Learn how TruPath Genome can help you unlock long-distance genomic insights.

References

  1. Benchmark: Genome in a Bottle NIST T2T-Q100 HG002 SV v1.1 truth set.
  2. Calculations based on internal Illumina estimates and “Clinical long-read genome sequencing for rare disease diagnostics” publication by de Bitter et al.

Supporting data footnotes

  1. The most accurate genome
    Illumina SBS Novaseq 1.4: IDPF libraries sequenced on 1.4SW NovaSeq X 10B Sequenced, analysed with DRAGEN analysis 4.5.1
    TruPath Genome SMW: Standard extracted DNA sequenced with TruPath Genome, analysed with DRAGEN analysis 4.5.1, XX63 technical replicates.
    TruPath Genome HMW: HMW extraction sequenced with TruPath Genome, analysed with DRAGEN analysis 4.5.1, XX64 technical replicates.
    Low MapQ defined as MapQ<10
    UG100 source: https://cdn.sanity.io/files/l7780ks7/production-2024/0a1b6a62a6da3e3fcafb81cad4c8ff2ffe85dd41.pdf
    PacBio SPRQ: downloaded from https://downloads.pacbcloud.com/public/revio/2024Q4/WGS/GIAB_trio/HG002_rep1/
    https://downloads.pacbcloud.com/public/revio/2024Q4/WGS/GIAB_trio/HG002_rep1/analysis/v3.0.2/
    Element Biosciences 1kb: https://www.biorxiv.org/content/10.1101/2025.06.05.657102v1, supplementary table 5, stratification set to ‘All’, ‘Type’ set to ‘All’, Variant_Caller set to ‘deepvariant_vg_pangenome_aware’

  2. Expanded genetic content unlocks new insights
    Pacbio SPRQ: downloaded from https://downloads.pacbcloud.com/public/revio/2024Q4/WGS/GIAB_trio/HG002_rep1/
    https://downloads.pacbcloud.com/public/revio/2024Q4/WGS/GIAB_trio/HG002_rep1/analysis/v3.0.2/
    https://epi2me.nanoporetech.com/giab-2025.01/

  3. A faster, more scalable solution for long-range genomic insights
    Comparable workflow for clinical translational research assumes no flow cell reuse and >30x coverage.
    Calculations based on internal estimates. Based on “Clinical long-read genome sequencing for rare disease Diagnostics”, de Bitter et al​.