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Long-Read Sequencing 

HiFi Long-Read
Whole Genome Sequencing (HiFi LR-WGS)

Increase Detection Yield for Rare Diseases

Over 7,000 rare diseases affect more than 300 million people worldwide, with about 80% having a genetic origin.¹ In recent years, NGS-based WES and WGS have played a crucial role in rare diseases. However, these methods provide answers in only about 30-40% of cases².

 

Short-read sequencing struggles to detect certain types of variants. This leads to missed diagnoses and requires additional, costly testing. In contrast, LRS overcomes these technical barriers. Studies show LRS can reduce missed variants by >93%³ and increase diagnostic yield by >10%⁴.

Comparison between LR-WGS with short-read and arrays

A New Standard of Rare Disease Genetics with LR-WGS

Berry Genomics advances clinical genetics with a high-accuracy HiFi long-read whole-genome sequencing (HiFi LR-WGS) solution designed for rare disease analysis. It helps clinicians and researchers uncover disease-causing variants that short-read NGS may miss. With high accuracy, genome-wide coverage, and improved resolution of complex regions, HiFi LR-WGS supports more confident analysis of rare and challenging cases.

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By reducing false calls and improving structural variant coverage compared with short-read WGS, HiFi LR-WGS supports more confident analysis for physicians and researchers to investigate the challenging cases.

Internal comparison data: WGS variant calling accuracy measured as false-positives (red) and false-negatives (blue) with reference HG002 (both 35x, benchmark NISTv0.6)

Key Capabilities of HiFi LR-WGS

Haplotype Phasing

Distinguish between maternal and paternal alleles without parental samples

  • Cis vs. Trans: Determine if two mutations are on the same or opposite chromosomes (critical for autosomal recessive conditions)

  • Pseudogenes: Accurately separate functional genes from homologous regions

Structural Variant (SV) Detection

Detects complex SVs often missed by short-read NGS, including large inversions and translocations

Repeat Expansion Analysis

Long reads (>15kb) span entire repetitive regions (from STRs to VNTRs)

  • Accurate Sizing: Counts repeat numbers precisely

  • Interruptions: Identifies sequence interruptions that may correlate with disease risk

Methylation Analysis

Directly detects DNA methylation patterns during sequencing, which is critical for imprinting disorders (e.g., Prader-Willi Syndrome) and some X-linked conditions

Send-out Testing

When considering our send-out sequencing services:

  1. Consultation: Contact our team for the most current test specifications.

  2. Sample Preparation: Check sample types and shipment requirements to ensure high-quality results. Please check your local export regulations and logistics partners.

  3. Submission: Contact Xcelom when placing an order. Include the completed Test Request and Consent Form, along with any required documents.

Sample Requirements

Peripheral Blood: 2 mL in EDTA tube

Long-fragment gDNA

Transport Conditions

2-8℃, arrive within 72 hours
Dry ice transportation, arrive within 5 calendar days

Deliverable

Raw Data

ACMG Reporting: ​Selected Variants Reported Associated with the Provided Phenotype*:

  • Single-nucleotide variants (SNVs)/ Insertions and deletions (InDels)

  • Copy number variations (CNVs)

  • Structural variations (SVs)

  • Absence of heterozygosity (AOH) / Uniparental disomy (UPD, for Trio only)

  • Mitochondrial mutations (SNVs/InDels)

  • Tandem repeats/Dynamic variants in 63 clinically relevant genes

  • Methylation abnormalities for 8 diseases

  • ACMG secondary findings

Turnaround Time (TAT)

34 working days

End-to-End Technology Transfer

Berry Genomics and Xcelom provide a dedicated service for the implementation of HiFi LR-WGS solutions. We deliver comprehensive support ranging from lab workflow setup to staff training.

We specialize in bioinformatics and analysis support, helping laboratories master the complexities of variant annotation and interpretation. Our tailored software solutions streamline the workflow and assist with ACMG classification by automatically integrating relevant public databases.

Resources

References:

1. Rare Genetic Diseases. National Institutes of Health. Accessed June, 2025. https://www.genome.gov/dna-day/15-ways/rare-genetic-diseases

2. Wright CF, FitzPatrick DR, Firth HV. Paediatric genomics: diagnosing rare disease in children. Nat Rev Genet. 2018;19(5):253-268. 

3. Höps W, Weiss MM, Derks R, et al. HiFi long-read genomes for difficult-to-detect, clinically relevant variants. Am J Hum Genet. 2025;112(2):450-456.

4. Farrow, Emily et al. O24: Unveiling the power of HiFi genome sequencing: One test to rule them all? Genetics in Medicine Open. Volume 2, 101471.

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