Making High-Performance Sequencing More Accessible

Discover how flexible, high-quality workflows can help labs scale next-generation sequencing with greater efficiency

InterviewingBellal MoghisBrought to you byRoche and Lab Manager
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Bellal Moghis, director of US marketing for sequencing and life sciences at Roche

CREDIT: Roche

Bellal Moghis is the director of US marketing for sequencing and life sciences at Roche, where he leads commercialization strategy for next-generation sequencing solutions. With more than 15 years of experience spanning product management, strategic marketing, and genomics R&D, he has led the launch and growth of innovative technologies across oncology, clinical diagnostics, and life science research. Prior to Roche, Bellal held leadership roles at Agilent Technologies and Illumina. He holds a Master of Science in biological sciences and an MBA with a concentration in marketing and finance.

Q: What are the biggest hurdles laboratories face in sequencing today?

A: Many of the challenges laboratories face today are practical, operational ones. Throughput is certainly one of them. Labs need to scale sequencing without creating bottlenecks or dramatically increasing costs. The challenge is that some of the best sequencing economics are tied to the highest-throughput systems, which often require very large batches to reach their advertised cost per genome. Mid-throughput laboratories, growing sequencing centers, and many research institutions, however, need a more flexible approach. They want to achieve similar cost efficiencies while working with smaller batches and maintaining the ability to scale as demand increases.

Speed is another challenge. For some research projects, waiting an extra day or two may not matter, but in other cases, turnaround time becomes much more important. The ability to move from sample to sequencing results within hours instead of days can fundamentally change how laboratories approach those workflows.

Finally, laboratories increasingly need support beyond the instrument itself. As sequencing technologies become more sophisticated, many researchers want complete workflow solutions that help them integrate new technologies into existing applications rather than having to build everything from scratch.

Q: How does sequencing by expansion (SBX) technology address these challenges?

A: SBX approaches sequencing differently from conventional technologies. Most sequencing platforms determine the DNA sequence by adding bases one at a time and taking repeated optical measurements throughout the process. SBX takes a different approach by using nanopores, but instead of passing native DNA through the pore, it sequences a surrogate molecule called an Xpandomer.

That distinction is important because DNA itself is a very small molecule. When it passes through a nanopore, the signal can be difficult to resolve with high precision. The surrogate molecule used in SBX is approximately 50 times larger than the DNA molecule it represents, producing a much stronger signal and a higher signal-to-noise ratio.

The goal is to avoid the trade-offs that laboratories have traditionally faced. By combining nanopore sequencing with the larger surrogate molecule, SBX is designed to deliver speed without compromising data quality. It enables sequencing in as little as four hours while maintaining data quality that is comparable to or better than that of existing sequencing platforms.

Q: How can laboratories adapt to different sequencing workloads and throughput requirements?

A: That often comes down to having enough flexibility to match sequencing capacity to the work at hand. With AXELIOS 1, a laboratory performing routine whole-genome sequencing can batch 16 samples and achieve attractive sequencing economics without waiting to accumulate much larger sample numbers. At the same time, laboratories that eventually need to process 64 genomes can simply queue multiple runs without additional intervention.

There are also situations where cost is not the primary consideration. If a laboratory needs rapid turnaround—for example, to perform trio-based family genomic studies—it may not be practical to wait until additional samples arrive. In those cases, laboratories can use ultra-rapid applications, such as SBX-Fast, to move from sample to sequencing data within a single work shift.

Importantly, these different workflows use the same instrument and the same reagents, allowing laboratories to switch between routine, high-efficiency sequencing and rapid- response workflows without adopting separate platforms.

Q: How should lab managers evaluate the performance requirements of their sequencing applications?

A: Different sequencing applications can have very different performance requirements, so lab managers should start by considering which characteristics matter most for the application. Whole-genome sequencing, for example, places a high value on sequencing accuracy, while quantitative applications such as RNA sequencing may prioritize read counts and throughput.

The AXELIOS 1 system has two run modes designed around those different requirements: duplex for high-accuracy sequencing and simplex for quantitative applications. Duplex sequencing typically provides quality scores of Q38, which is more than enough for high-accuracy applications. Simplex workflows offer high throughput and longer read lengths for counting applications where 99.3 percent accuracy is sufficient, roughly equating to Q22.

Q: Which applications or customer types do you think will benefit most from the flexibility of the AXELIOS 1 platform?

A: Whole-genome sequencing is naturally one of the primary applications because many laboratories immediately recognize the advantages of reducing turnaround time.

But beyond whole-genome sequencing, some of the strongest interest has come from quantitative applications, particularly single-cell sequencing. Researchers performing single-cell studies generate enormous numbers of sequencing reads, and sequencing cost can quickly become a limiting factor. By substantially reducing the cost per million reads through the SBX-Simplex workflow, laboratories can expand the scale of these experiments and process more samples than was previously practical. For many service laboratories, that changes the economics of their business. They’re able to increase capacity and offer applications that may not have been financially feasible before.

Q: What should laboratories consider when deciding whether to adopt a new sequencing technology?

A: Adopting new technology can be challenging, but in a rapidly evolving field, it can also be risky to let advantages pass you by. Engaging early with a new sequencing technology gives laboratories the opportunity to leverage those advantages sooner. That could mean publishing sooner or with more insights, enabling commercial laboratories to compete more effectively, or bringing greater capabilities to local researchers.

Importantly, customers are often the ones who identify applications that weren’t initially envisioned. Once they have the technology in their hands, they can determine how its capabilities might address their own specific challenges. As the technology matures and becomes more widely adopted, we will also continue to consider potential clinical research and eventually diagnostic applications.

Q: What does the future look like for AXELIOS 1?

A: At Roche, we have decades of experience supporting laboratories worldwide, and we plan to continue building around the AXELIOS 1 system. That includes developing the broader ecosystem around the platform so laboratories can integrate sequencing into workflows that address their specific needs.

Ultimately, investing early in technology can put laboratories in a better position to realize benefits now and in the future. The goal is to give researchers the flexibility to explore new applications while continuing to build the capabilities and solutions that will support the sequencing community as its needs evolve.

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  • Image of Bellal Moghis

    Bellal Moghis is the director of US marketing for sequencing and life sciences at Roche, where he leads commercialization strategy for next-generation sequencing solutions. With more than 15 years of experience spanning product management, strategic marketing, and genomics R&D, he has led the launch and growth of innovative technologies across oncology, clinical diagnostics, and life science research. Prior to Roche, Bellal held leadership roles at Agilent Technologies and Illumina. He holds a Master of Science in biological sciences and an MBA with a concentration in marketing and finance.

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