What happens when one of the world’s top genomics service providers gets their hands on cutting-edge chemistry? Big things. At Signios Biosciences, innovation is the engine that drives powerful discoveries across clinical, pharmaceutical, and academic research worldwide. With a team of over 1,200 spanning the U.S. and India, they’re making high-quality genomic insights more accessible than ever.
In this interview, we caught up with Dr. Harsha Gowda, Director and Senior Principal Scientist of Research and Operations, to talk about what’s new, what’s next, and how SPRQ chemistry on the Revio system is changing what they’re able to achieve.
The key takeaway? More data per SMRT Cell, more samples sequenced, and more flexibility for customers around the world.
Q: What can you tell us about your role at Signios Biosciences?
Dr. Harsha Gowda: I am the Director and Senior Principal Scientist of Research and Operations at Signios Biosciences. As an end-to end service provider, Signios Biosciences handles everything from sample prep to sequencing and data analysis, and I oversee all the lab work here, both on the short-read and long-read front.
Q: What would you say makes Signios Biosciences special as a service provider?
We have a proven track record of offering genomic services for almost 10 years. I think what’s special about Signios Biosciences is the level of consultation and service that we offer, starting even from initial project discussions and experimental design. Some investigators may want to set up their experiment based on the possibilities downstream, so we work with them to configure the experiment so that they can leverage downstream technologies to get the best output possible. We also perform data analysis and interpretation, so if a customer wants to simply send us a sample, we can handle it end-to-end from extraction to data analysis and interpretation and walk them through the data.
We provide a broad suite of services, so we can accommodate projects that run the gamut of genomics. In addition to whole genome sequencing or RNA sequencing, we offer single-cell sequencing, spatial transcriptomic profiling, and amplicon sequencing, as well as custom designs to detect some of the genes that are not represented by standard off-the-shelf kits. So, if a customer wants to do multiomics from the same sample, we perform everything in-house so that they only have to work with one provider from one sample.
Although there are some other service providers who offer such services, the level of attention we provide is something special, I think. And based on the customer retention that we have seen over the years, most people who work with us largely stay with us for many of their projects.
Q: With such a variety of applications, are you seeing any trends emerging with the different sequencing technologies available?
I’ve been seeing the adoption of long reads increase for many applications as the cost barrier continues to be reduced. I’ve noticed this trend with PureTarget in particular, for customers who have these repeat regions associated with important medical conditions for which short reads are not best suited to address those questions. I think long reads will continue to rule that space more and more as we go forward.
Q: How has the addition of SPRQ chemistry to the Revio system changed your data output?
We were very excited to learn about SPRQ chemistry. Its ability to generate more data per SMRT Cell with less DNA input—without increasing costs—is a definite game-changer.
Switching over to the new chemistry was a smooth experience. We were blown away by the amount of data from our first run, and we’ve consistently seen great results.
| Revio v1 chemistry | SPRQ chemistry | |
|---|---|---|
| HiFi reads | 6.07 M | 7.35 M |
| HiFi read yield | 95.07 Gb | 139.Gb |
| HiFi read length (mean) | 15.67 kb | 18.98 kb |
| HiFi read length (median, bp) | 15,749 | 18,790 |
| Signios Biosciences sample whole genome sequencing data for runs on Revio v1 and SPRQ chemistry. | ||
We have now successfully sequenced whole genome libraries and Kinnex full-length RNA libraries with SPRQ. With high-quality whole genome samples, we’re achieving around 140 Gb per SMRT Cell, and for Kinnex full-length RNA libraries, we’re reaching 160–170 Gb per SMRT Cell. It’s truly fascinating to see such a significant boost in data output with SPRQ chemistry.
Q: What has this improvement meant for your customers?
Since it dramatically increases the data output per SMRT Cell, this naturally means a lower price per sample for many customers if they are multiplexing or are trying to get better depth for a given sample. Also with increased yield, 2 human genomes can now be sequenced at 20X on a single SMRT Cell, significantly reducing cost per sample.
We’re seeing this development help our customers overcome a sample input barrier, because in previous scenarios we’ve had to set lower expectations for customers when sample requirements were not met. That is no longer the case. SPRQ chemistry suddenly opens up the possibility for HiFi sequencing for customers with difficult samples.
We’re seeing SPRQ benefit customers with low tissue or biopsy material, but also for those working with organisms like plants or marine animals for which extracting high-molecular weight DNA can be difficult. This reduction in input requirement suddenly has enabled some of these samples to be sequenced with very low amounts of starting material.
Q: Looking ahead, where do you see the biggest potential for long-read sequencing?
I can think of several areas where I could see the most growth for long-read sequencing: First, I think long-read genome sequencing will expand to even the most complex genomes –– It’s a no brainer that at any given moment you’d always opt for long-read sequencing, now no matter the genome.
Second, gene therapy companies that are editing genomes want a holistic view of what is happening across the genome after the edit, so I think long-read sequencing will continue to offer a huge benefit there. I also see a lot more activity with long-read sequencing for isoforms, which previously were largely coming from short reads. Although you could gain some insight from short reads, it was not necessarily as accurate because of the nature of the technology. I think there will be more mapping of isoforms that are not well characterized and exploration of the transcriptome like never before, and these applications will benefit significantly from long-read sequencing.
Finally, we’re seeing growing interest in novel applications including Fiber-seq for chromatin architecture. I also see long-read applications increasing for targeted sequencing, especially with the availability of PureTarget, because these long repeats in the genome are best mapped using a long-read platform.
Signios Biosciences’s experience with SPRQ chemistry shows how influential HiFi sequencing is in real world scenarios. With higher data yields and lower sample input needs, they’re now able to take on all kinds of projects—from clinical research to tough genomes that used to be a challenge. And the best part? Researchers and clinicians are getting more of the genomic info they need, faster and with fewer roadblocks. That’s the kind of impact PacBio is here for: helping more labs, in more places, get the quality data they need to push discovery forward.
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