Diverse applications of long-read sequencing: stories from chemagic users.

Population-scale long read sequencing unveils novel pathogenic variants

One of the earliest and largest LRS population studies run to date is performed on 3622 Icelanders. Extraction on chemagic 360 instruments obtained an N50 of ~20 kb with some reads > 100 kb (especially in non-sheared samples). Coupled with downstream Oxford Nanopore sequencing on the PromethION system, > 99% of samples achieved ≥ 10x coverage threshold, proving that automated sample preparation was key to ensuring batch-to-batch consistency.¹

The study uncovered 133, 886 unique structural variants from 50 bp to >1 Mb in length. Some of these variants, which would otherwise have been missed by short-read sequencing, have helped uncover genes with direct links to diseases and physical traits.² Aside from structural variants, LRS better resolved highly complex repetitive regions and epigenetic modifications, expanding our understanding of the human genome.

This study was the first of its kind, boldly applying long-read sequencing at population scale and harnessing Iceland’s well-documented genealogy and relatively homogenous genetic background to enable powerful genotype-phenotype associations.

The study set in motion the drive towards personalized medicine and proactive health choices based on our genetic makeup. It signaled the start of further large-scale population studies, supported by and made technically and economically feasible with automated chemagic separation technology.^3,4,5

Rare disease research for childhood disorders

At the Children’s Mercy Hospital, chemagic extractions have supported long-read PacBio HiFi sequencing with > 1500 genomes sequenced, and 50+ clinical cases validated. Dr. Emily Farrow highlighted how chemagic technology has consistently delivered HMW DNA with N50 ~20 kb at yields of 40 µg from just 1 ml of blood for over 10 years.⁶ Compared to manual methods, the chemagic workflow offered a 75 % reduction in hands-on time, 6.4 x faster total processing (16 h vs. 2.5 h) and 2.4 x higher throughput. Importantly, long read sequencing demonstrated a 52 % diagnostic rate with a single assay, avoiding the costs, time, and blood draws needed for running multiple assays, e.g., karyotyping, microarrays, expansion testing, exome, and methylation analysis.

For childhood diseases, this is especially meaningful, helping families get answers faster with fewer tests and less stress.⁷

Genome-wide epigenetic signature detection in genetic diseases

Researchers at Radboud University Medical Center recently reported a methylation and genome-wide episignature robustly detectable in 83 samples (including 10 trios) using chemagic HMW DNA extraction with PacBio HiFi LRS.⁸ The workflow achieved 96 % success in imprinting disorder diagnosis and 91.7 % accuracy in episignature-based variant classification. Extraction was performed on archived blood samples and LRS enabled detection of 5mC methylation without the need for bisulfite treatment, which can degrade DNA and create artefacts.

Despite 12 sequencing batches, no batch effects were observed, and successful methylation calling was seen at 15 x and 30 x coverage indicating a consistent quality of sample processing.

The power of LRS to uncover novel CpG sites (5 % more than short read methods), is highly dependent on the ability of the extraction method to preserve methylation marks. With consistent HMW DNA quality, researchers could perform haplotype-resolved methylation analysis across complex genomic regions previously inaccessible to short-read methods.

Future proof your research

These stories by chemagic users paint a compelling story of where genomics is headed, toward greater scale, deeper resolution, and more clinically meaningful insights. But the quality of every discovery begins long before the sequencer runs - it begins at the extraction step.

The chemagic separation technology has been delivering consistent, reliable yields of high-integrity, ultrapure nucleic acids that laboratories at the forefront of genetic research trust and rely upon. Developed in Germany and a full value chain provider of both chemagic instrumentation and reagents, Revvity provides excellent support and automation expertise. All at a speed and cost that makes population-scale and clinically urgent work genuinely feasible.

Whether you are mapping the genetic architecture of a nation, solving a child's diagnostic odyssey, or decoding the epigenetic language of disease, the foundation of your research deserves the same ambition as your science. With chemagic technology, you are not just extracting DNA, you are increasing the chances of success for upcoming experiments and breakthroughs yet to come.