In genomics, every lab is chasing the same trio of workflow priorities: working toward results that are accurate, flexible in application, and efficient in practice. For labs focused on targeted sequencing, the stakes are even higher. The right approach delivers trusted results, supports a broad range of applications, and fits how labs actually work.
With long read lengths and 99.9% single-read accuracy, HiFi long-read sequencing is uniquely well-suited for targeted sequencing projects of all scales, spanning amplicon panels, repeat expansion analysis, and hybrid capture workflows.
Access expert resources on long-range PCR amplicon sequencing, CRISPR-Cas9 PCR-free enrichment with PureTarget, and hybrid capture to find the targeted resequencing strategy that fits your lab.
Why complex genomic regions matter for sequencing
Many of the loci most worth targeting in a sequencing experiment are also the most structurally difficult to sequence. Tandem repeat expansions underlie dozens of neurological and neuromuscular conditions, among them Huntington’s disease, fragile X syndrome, myotonic dystrophy, and multiple spinocerebellar ataxias. The causal variants are expansions of short sequence motifs, sometimes repeated hundreds or thousands of times, forming structures far longer than a short read can span. Detecting and accurately sizing them requires reads long enough to cover the full repeat tract in a single pass.
Relatedly, segmental duplications, which account for roughly 7% of the human genome, are stretches of nearly identical sequence that appear in multiple genomic locations. Short reads mapping to these regions frequently fail to align uniquely, creating coverage gaps and false negatives that persist even at high sequencing depth. Structural variants, including inversions, translocations, duplications, and deletions larger than 50 base pairs, are similarly undercalled, as their boundaries often exceed what a single short read can span.
The case for targeted sequencing with long reads
When reads are shorter than the genomic feature being queried, alignment becomes ambiguous, coverage drops unevenly, and variants can go undetected. Repetitive regions, high-GC loci, tandem repeat expansions, and complex structural variants all present this challenge, and they are common in precisely the loci most relevant to disease biology and pharmacogenomics.
Benefits of targeted sequencing
HiFi sequencing produces read lengths that routinely span 10 to 20 kb alongside greater than 99% single-read accuracy, delivering the ability to resolve difficult regions with a confidence other sequencing approaches cannot reliably match. And because native DNA methylation including 5mC, 5hmC, and 6mA is captured in every run without additional library prep, you get epigenomic context alongside your variant calls at no extra cost.
Benchtop access to HiFi targeted sequencing with Vega
For labs looking to apply this resolution to their own targeted sequencing projects, the Vega system is PacBio’s first low- to medium-throughput benchtop HiFi sequencing platform. It delivers the proven accuracy of the Revio system in a compact instrument designed for individual labs, addressing one of the top customer requests for HiFi sequencing, offering comparable performance at a lower capital and physical footprint.
HiFi technology on Vega is optimized for targeted sequencing, and powers amplicon, hybrid capture, and PureTarget panels.
Three targeted approaches and when to choose
Designed for individual labs, it matches the variant calling accuracy of the Revio system, a technology backed by 1,350+ peer-reviewed publications in 2025, in a compact footprint with push-button run setup, on-instrument primary analysis, and only two consumables.
A single Vega SMRT Cell supports a wide range of targeted sequencing workflows in a single run:
- >1,000 amplicons per run
- 96 PureTarget repeat expansion and carrier panels per run
SPRQ-Nx chemistry coming soon to Vega
SPRQ-Nx chemistry is already available on the Revio system, and is coming soon to Vega. This update will significantly expand what the platform can do, bringing meaningful improvements across yield, input requirements, turnaround, and multiomics detection:
- Higher yield: 80–90 Gb per SMRT Cell at 15–20 kb read lengths, a ~50% increase over Vega v1 chemistry
- Lower DNA input: 500 ng vs. 2 µg—a fourfold reduction, opening access to precious or limited samples
- Faster turnaround: 2- and 4-hour movie times for short amplicons, enabling same-day results and single-shift workflows
- Expanded multiomics (PureTarget and WGS): added 5hmC detection and optimized 5mC and 6mA performance—native methylation calling in every run, no extra library prep required
- Support for 21 CFR Part 11 compliance: audit tracking and instrument login controls to support regulated workflows, with PacBio platform commitment through 2032
One platform, consolidated workflows
One of the most practical advantages of HiFi sequencing on Vega is the ability to consolidate what previously required multiple assays into a single, streamlined workflow. Rather than running separate experiments for variant detection, repeat expansion analysis, and epigenetic profiling, HiFi captures all of that information in a single sequencing run.
For labs managing multiple project types, this consolidation reduces reagent overhead, shortens time to results, and simplifies validation, particularly important for teams working toward clinical or regulated applications.
Ready to explore targeted sequencing with HiFi?
For labs ready to bring high-accuracy targeted sequencing in-house, the Vega system is available now as a cost-effective, low-footprint platform, and with SPRQ-Nx chemistry set to expand what your sequencing can accomplish.
Access expert resources on long-range PCR amplicon sequencing, PureTarget PCR-free enrichment, and hybrid capture, and find the right approach for getting more comprehensive answers from a single assay.