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Hitting the Target With NGS Advances

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This year’s Advances in Genome Biology and Technology (AGBT) meeting showcased some of the most exciting developments in genomic technology. Twist Bioscience, who specialize in DNA synthesis, showcased their new target enrichment solutions at this year's conference. We caught up with Twist CEO Emily Leproust to discuss the importance of target enrichment in next generation sequencing (NGS) and the advancements in the field that caught her eye at AGBT.  

Ruairi Mackenzie (RM): Why is target enrichment important in NGS workflows?

Emily Leproust (EL): The goal of target enrichment is to make sequencing as efficient as possible. Target enrichment enables researchers to focus their research to specific genetic variants. Customers use target enrichment to streamline their laboratory workflows and data analysis. A key benefit of target enrichment is that it enables labs to process many more samples on a single sequencing instrument when compared to whole genome sequencing. Target enrichment is important in the detection of very low frequency variants using cell-free DNA samples.

We believe we are the only company to offer double-stranded DNA (dsDNA) probes within a comprehensive target enrichment kit used for exome and targeted sequencing. Using dsDNA as opposed to single-stranded DNA, or RNA, during next generation sequencing preparation may avoid the problem of deamination (removal of an amino group). Deamination interferes with the detection of infrequent gene mutations, and may hinder genetic results and clinical diagnosis, particularly in cancer.   

Molly Campbell (MC): How specifically does the NGS target enrichment product line accelerate hybridization? What technologies have enabled their development? 

EL: Twist’s NGS target enrichment workflows enable customers to move from sample to sequencer in a single day. Twist’s Fast Hybridization and Wash Kit is a new system which has been designed to both save time and improve performance. A highly optimized buffer system decreases hybridization time to as little as 15 minutes. The Fast hybridization workflow is ideal for all targeted sequencing applications, including whole exome and custom panels.


RM: How does Twist use data to drive its panel design process?

EL: At Twist, our foundation is to apply engineering principles to panel development and design. We take an iterative learning approach to optimize our target enrichment designs. Our silicon-based oligonucleotide production process provides us with the ability to rapidly generate many NGS panels. During our product development process, we applied this iterative approach to build and test multiple panel designs for a specific application or target region. Using this technique, we can accurately predict which target capture probes will perform well and which probes should not be included in the design.  We work closely with our R&D team and our customers to experimentally validate our designs, continue to deliver optimal performance, and enable new applications.


MC: In the development of novel NGS products, is there input from scientists in the field that will eventually use these products? 

EL: Input from the scientific community and our customers is an important consideration for product development at Twist. For example, our customers told us they wanted the ability to complete the entire Twist target enrichment workflow in a single workday. This is especially important to customers running large labs which process thousands of samples per year. This feedback helped further encourage our development and launch of the Twist Fast Hybridization and Wash Kit. Another key benefit of working closely with scientists in the field is to gather insight into the next big application in NGS. By working closely with customers, Twist can continue to make innovative contributions to leading edge scientific research.


RM: What applications and innovations in NGS have impressed you this year at AGBT? 

EL: AGBT provides a great showcase of the latest innovations in NGS. In 2019, there were several clear trends and areas of significant innovation. A major theme running throughout the conference is the need for high quality tools which can be applied towards clinical applications. NGS has moved quickly from the lab bench to the clinical researcher. That trend will continue to drive technological innovation. In terms of new technologies, the growth of high throughput sequencing instruments has enabled new of scientific questions to be addressed by NGS. Large scale single cell studies are growing in size and importance. Spatial genomics is a new emerging technology which is increasingly being used in immune-oncology applications.

Emily Leproust was speaking to Molly Campbell and Ruairi J Mackenzie, Science Writers for Technology Networks