The critical importance of high molecular weight DNA for long-read sequencing.

In the field of genomic research, whole genome sequencing (WGS) and especially long-read sequencing (LRS) are emerging as transformative technologies that promise to revolutionize our understanding of genetic information. As we stand at this technological crossroad, one crucial factor often overlooked is the quality of DNA extraction—specifically, the need for high molecular weight (HMW) DNA to fully leverage the power of long-read sequencing platforms.

A growing scientific movement

The numbers tell a compelling story: in 2017, approximately 802 scientific publications featured long-read sequencing with error rates ranging between 10 to 15%. By 2025, this number is projected to be over 4000 with error rates now at 0.01-0.1%. This rapid advancement has helped achieve clinical grade accuracy with sensitivities and specificities consistently exceeding 99%, even across structural variants, repeat expansions, methylation patterns and pseudogene-associated variants that challenge short-read methods (1, 2, 3). With a compound annual growth rate exceeding 20%, the long-read sequencing market represents one of the fastest-growing segments in genomic research.

This is not merely a passing trend but a fundamental shift in how we approach genomic analysis. The question is not whether long-read sequencing will become essential—it is whether your lab will be prepared when it does. Laboratories at the forefront of genetic analysis are already condensing the number of genetic tests offered from around 100 to only ~10 by using WGS and LRS(4).

The critical DNA quality factor

Imagine spending years collecting and storing biological samples, only to discover they are unsuitable for the most advanced analytical techniques when you need them. This scenario is playing out in laboratories worldwide as researchers attempt to use inadequately preserved DNA samples for long-read sequencing.

The chemagic technology offers a solution specifically designed for automated HMW DNA extraction at scalable throughputs—the exact requirements for successful long-read sequencing applications. HMW DNA is crucial as excessive fragmentation reduces the read length, disrupts variant regions for precise resolution, limits haplotype phasing and reduces the detection of epigenetic marks. The chemagic technology, when compared with an alternative automated extraction platform, demonstrated a ~1-2-fold greater extraction efficiency of HMW DNA fragments (> 50 kb) alongside higher overall yields, showing differences in extraction methods can impact HMW DNA extraction efficiency (7).

With regards to compatibility with downstream long-read sequencing platforms, the chemagic technology was employed in the largest long read sequencing population study done to date with Oxford Nanopore sequencing, providing the best combination of long read lengths and high data output (GB)(5). Similarly, the chemagic technology has been used successfully with SMRT sequencing (PacBio), with over 1500 HiFi genomes sequenced and growing on a weekly basis as part of the “Genomic Answers for Kids” research program at the Children’s Mercy Hospital (6). The chemagic automated nucleic acid purification system ensures that the DNA you extract today will be suitable for the analytical methods of tomorrow.

Real-world impact

The practical applications of this technology are already evident across multiple fields. In Iceland, researchers used chemagic technology-extracted DNA for long-read sequencing to analyze 3,622 individuals, providing unprecedented insights into structural variants linked to human diseases(5). In the field of rare disease and developmental disorders, the chemagic technology has been supporting pediatric research for over a decade and combined with long read sequencing has resulted in a diagnostic yield of over 50%(6). Cancer research has also benefited, with scientists using this approach to precisely characterize genomic duplications and complex insertion-deletion variants in cancer genetics—variants that would be difficult or impossible to identify with traditional sequencing methods(8, 9).

The everyday relevance

Consider this everyday parallel: Many people stored their precious family photos as low-resolution digital images in the early 2000s, thinking the quality was sufficient. Today, as high-definition displays become standard, those images appear pixelated and unsuitable for modern viewing. Similarly, DNA samples extracted using conventional methods may prove inadequate for tomorrow's analytical needs.

Just as professional photographers always capture in the highest resolution possible to "future-proof" their work, forward-thinking laboratories are adopting HMW DNA extraction methods to ensure their samples remain valuable assets for years to come.

Preparing for the future

The message is clear: if you are involved in any aspect of genetic research or diagnostics, the quality of your DNA extraction methodology is not just a technical detail—it is a strategic decision that will determine your ability to participate in the next generation of genomic discovery.

The chemagic solution offers scalable automation combined with superior DNA quality, ensuring that your laboratory remains at the forefront of genomic research. By implementing this technology today, you are not just improving current workflows; you are making an investment in your laboratory's future capabilities.

As the scientific community increasingly embraces long-read sequencing for its ability to resolve complex genomic regions and structural variants, the divide between laboratories equipped for this technology and those left behind will only widen. The question is: which side of this divide will your laboratory be on?

For research use only. Not for use in diagnostic procedures.