As one of China’s most prominent clinical genomics companies, Berry Genomics has a sharp focus on the prevention of genetic birth defects. Their team is constantly on the search for new ways to do more, faster. They recently added a new tool to help achieve their goals: the Vega system. Their Vega systems now join Berry’s fleet of HiFi platforms, which have already sequenced more than 300,000 Thalassemia samples and helped to contribute a 3–5% increase in diagnosis rate compared to traditional assays.
We sat down with Dr. Aiping Mao, Vice Director of R&D at Berry Genomics, to talk about how the need for exceptional accuracy in clinical applications drove their adoption of HiFi sequencing and how this new wave of long reads is having an impact on clinical genomics and public health.
Q: What can you tell us about Berry Genomics and your role within the company?
Dr. Aiping Mao: Berry Genomics is dedicated to the large-scale clinical application for high-throughput technologies by providing a one-stop solution for the screening and diagnosis of human genetic diseases.
Berry has been one of the pioneering companies to apply short-read sequencing based noninvasive prenatal testing (NIPT) for prenatal screening, CNV-Seq for prenatal diagnosis, whole exome sequencing, whole genome sequencing. And now with PacBio technology, long-read sequencing for complex single gene disorders. We serve over 2000 hospitals and institutions with our work on perinatal screening and diagnosis, with 8 million NIPT, 500,000 CNV-Seq, 200,000 whole exome sequencing trio tests, and now 400,000 target HiFi long-read sequencing tests for single-gene disorders in total.
I lead the R&D team at Berry, which includes assay designs, experimental procedures, and bioinformatics pipelines. I also lead the clinical research team, which designs and performs clinical studies in collaboration with experts in the field.
Q: What is a perspective Berry has that you think contributes to its success?
I would say there are two main perspectives for Berry’s success: clinical demand-driven and technology-driven. For the clinical demand, we focus on finding a solution for the unresolved issues for human genomics like complicated single-gene disorders, as well as localization, which helps the hospitals to run the whole workflow within the hospital and generate a localized database. For the technology aspect, Berry adopts the most advanced technologies like HiFi long-read sequencing to help with precision human clinical genomics. We have also developed and launched GENOisi, an AI-empowered system for clinical database based on 15 years of sequencing data, laboratory managing application from sample to report, as well as various tools for AI interactions.
Q: Since Berry Genomics began specializing in short-read sequencing and later moved to long reads, what motivated that technology shift for you?
As a leading company in clinical genomics, Berry Genomics always focuses on the clinical demand first, and then we make our best efforts solve the clinical problems with state-of-the-art technologies. There are about 400 single-gene disorders that are challenging for short-read sequencing because of their complex genetic architecture. As a prominent example, the inherited blood disorder Thalassemia is a large threat for human health in South China, where the carrier rate can reach as high as 10~25%. In the beginning, Berry had tried seeking a solution to Thalassemia and other complex single-gene disorders with short-read sequencing, but found the results were not satisfactory for these challenging disorders. This was what initially prompted us to move to PacBio long-read sequencing. The successful application of long-read Thalassemia assays for over 500 centers and over 300,000 clinical samples, with much positive feedback from our customers, has affirmed our choice of adopting PacBio HiFi long-read sequencing platforms.
Q: How do you see this long read-based Thalassemia assay impacting public health?
Right now, PCR-based methods are still very widely used in China. After we developed our long-read Thalassemia assay, we performed a series of clinical studies and initiated the Thalassemia Gene Atlas (TiGA) project to fully investigate the spectrum of Thalassemia variations. Through the TiGA project, we have tested over 5000 samples from 43 hospitals with HiFi sequencing that were not completely resolved by traditional assays like PCR, Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA).
With HiFi long-read sequencing, we found at least 20 novel large deletions or structural variations in the Thalassemia genes that have helped contribute to a 3–5% increase in diagnosis rate compared to traditional assays.
This is very important because Thalassemia’s high carrier rate translates to additional tests for many people and has changed how people in the field think about the molecular genetics of Thalassemia.
Q: What were your first reactions to hearing about the PacBio launch of Vega, the first benchtop HiFi system?
Initially I was skeptical as to how you can compact the functionality of a large sequencing instrument to a benchtop system without compromising the sequencing quality, but as soon as we started getting data, I quickly understood I shouldn’t have worried – the data is of very high quality and throughput and it is a valuable addition to our existing PacBio systems.
We currently have five Vega systems in the lab with an additional five planned this year. These Vega systems are a great fit for us because the smaller benchtop footprint and throughput is ideal for our targeted single-gene assays and our expansion into panels and whole-genome sequencing as well.
Overall, I think Vega is a perfect and promising benchtop sequencer for clinical genomics with its long HiFi reads, efficient turn-around-time, and easy operation.
Vega has also particularly accelerated our R&D process, because its ease of use no longer requires a specialized team to manage the sequencing, and with the faster run times, we can accomplish so much more in the same amount of time.
Q: What are your plans for the Vega system in the future?
We are currently working on transferring our assays that have been developed on Sequel II system to Vega, and this process has been going very smoothly so far because of the excellent performance of Vega. We are also expanding single-gene disorders into panels for many different applications. We are looking to long-read whole genome sequencing as a good solution to this as the cost continues to decrease and the compute power increases. Importantly, Berry Genomics will take Vega through the National Medical Products Administration (NMPA) regulatory review process in China with plans to support broad clinical applications.
Q: What is one thing you wish more people understood about HiFi sequencing in clinical genomics applications?
Accurate long-read sequencing is the most critical aspect for precision human clinical genomics, because it can resolve missed discoveries caused by the insufficient precision of earlier sequencing technologies.
We chose HiFi sequencing for its exceptional accuracy, which is essential for working with human samples and ensuring reliable results for whole genome sequencing, especially for clinical applications.
For Berry Genomics, the Vega system is a true catalyst for transformation. It is reshaping their ability to develop complex single-gene assays, speed up R&D, and impact public health.
As Berry expands from single-gene tests into broader panels, they are once again setting the pace for clinical genomics in China. With the help of Vega, Berry is making accurate, high-quality genomic insights more accessible and redefining what’s possible in the diagnosis and prevention of genetic disease.
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