Science Digest: Sequencing Technology is Evolving

Here’s What The Evolution Means For Your Lab

Sequencing is no longer just faster, it’s becoming smarter. Team KC Laboratory Informatics Consultant Haley Gallagher covers the latest innovations in sequencing technologies.

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Across the life sciences, researchers are embracing a new generation of sequencing technologies that don’t just deliver more data, but offer greater precision, clarity, and context. These innovations are already shifting what’s possible in diagnostics, translational research, and personalized medicine.

Take long-read sequencing, for example. Technologies like PacBio HiFi are helping scientists to assemble complete microbial genomes and resolve repetitive or complex regions that short reads often miss. PacBio HiFi is a sequencing technology that reads long pieces of DNA with very high accuracy by reading the same strand multiple times and averaging the results. The unique combination of long reads and high accuracy makes it ideal for complex regions compared to NGS sequencers.

What is Long-Read Sequencing?

According to the NHS, "Long-read sequencing is a form of next-generation sequencing (NGS) that can sequence long strands of DNA or RNA in one go, without breaking it up into smaller fragments."

PacBio HiFi technology has quickly gained market share and a reputation for reliability over traditional NGS sequencers. For example, Target ALS chose PacBio HiFi for one of the largest genetic ALS studies conducted to date, analyzing thousands of genomes to uncover complex mutations. Its long, accurate reads can detect structural variants and repeat expansions that standard NGS often misses, making it ideal for ALS research.

In oncology, new ultra-sensitive approaches, like PhasED-seq, are pushing the limits of circulating tumor DNA (ctDNA) detection in liquid biopsies. Unlike standard methods that look for single mutations, PhasED-seq tracks groups of linked mutations (phased variants) that are unique to each patient’s tumor, making detection more sensitive and specific. This allows for more accurate monitoring of minimal residual disease (MRD). For patients, this means a simple blood test can indicate if cancer is still present or coming back and make early detection more accessible. 

Hybrid strategies, such as combining optical genome mapping with next-gen sequencing, are surfacing complex mutations traditional tools often miss. Optical Genome Mapping (OGM) is a technology that uses fluorescent labels to visualize and map extremely long DNA molecules, allowing detection of large structural variations and copy number changes across the genome. It provides a detailed, genome-wide view of DNA alterations and is increasingly used in both research and clinical settings, especially for cancer diagnosis. OGM is a prime example of adapting established technologies to meet the evolving needs of the industry. As personalized medicine continues to advance, the demand for personalized diagnostics will naturally follow. By repurposing trusted tools in innovative ways, researchers are effectively addressing these emerging requirements.  

What’s even more exciting is the emergence of entirely new platforms, like Roche’s Sequencing by Expansion SBX, which rethinks how DNA is read by expanding molecules for easier, high-speed imaging. Instead of improving instrument capabilities, SBX technology essentially “stretches” DNA into longer molecules called Xpandomers, making it easier to read accurately and quickly. It offers very high accuracy, fast processing (sequencing multiple genomes per hour), and flexible read lengths. Initially, Roche will focus on diagnosing genetic disorders in critically ill newborns and their parents, with the goal of integrating it into routine clinical care.

Across our clients and network, we’re noticing that organizations leveraging these new technologies have a growing need for informatics systems that can keep up.  One of our consultants, Xandria Amash, weighed in on the trend–”These new technologies have brought variations in metadata, flow cell arrangements, sample sheet formatting, and more. We’re thinking critically about how to not only capture this new information, but future-proof it for what comes after it.” 

As sequencing becomes more powerful and nuanced, the demand for scalable, flexible data solutions in the lab is only going to grow. It’s an exciting time to be working at the intersection of biology and data and here at Karchem Consulting we are helping labs stay ahead of the curve: whether that means evaluating new platforms, optimizing data workflow, or implementing informatics systems built to support the next generation of scientific discovery.

To learn more, get in touch with us!