Next Generation Sequencing Takes a Leap Forward in 2018

Next Generation Sequencing (NGS) has progressed rapidly in recent years, with vastly enhanced data processing capacities being paired to far quicker read times. The start of 2018 has seen the launch of Thermo Fisher Scientific’s new line of of bench top sequencers, the Ion GeneStudio S5 Series, which includes three new sequencers and a new chip, the Ion 550.

We talked with Andy Felton, VP Product Management of Clinical Next-Generation Sequencing and Oncology at Thermo Fisher to hear more about this powerful new technology. 

Ruairi Mackenzie (RM): Your latest Series of Next-Generation Sequencers, the Ion GeneStudio S5 Series, has been described as having “unmatched flexibility”. What innovations have you made in the platform to deliver this flexibility?

Andy Felton (AF): The major innovation comes with the enhanced compute capability in the Ion GeneStudio S5 Plus and Ion GeneStudio S5 Prime systems for further improvement in  speed of analysis time – enabling analysis to be completed in as little as 30 minutes after the 2.5-hour sequencing run. These platforms have the fastest turn-around time and scalability of output of any bench top system today.

Additional innovation comes from our newly launched, high-output Ion 550 Chip, which offers up to 260M reads and 50 gigabases of output per day. This, along with our other Ion semiconductor chips (510/520/530/540), allows a single platform to scale efficiently from 2M reads and 0.5 gigabases of output to the daily 260M read levels of the Ion 550 chip. This unmatched flexibility enables customers to choose the appropriate chip that is relevant to their experiment and throughput requirement to maximize cost efficiencies while avoiding the need to choose from a range of instruments or wait to batch samples.

RM: The GeneStudio series is powered by your new series of Ion S5 chips, which includes the Ion 550 chip. What are the features of these new chips and to what processes are they specialised?

AF: The Ion 550 Chip is a new generation semiconductor chip by Thermo Fisher that continues the scaling of output for the Ion Torrent platform. We’ve developed a 300M pixel/well architecture with new surface chemistry to enhance signal to noise and generate high-quality, highly accurate reads out to 200 base pairs. Our raw accuracy runs at 99 percent for the entire length of the read, allowing the user to be confident in their sequencing and variant calling performance across a wide variety of applications.

In particular, the Ion 550 is well-suited for larger liquid biopsy assays, where high depth of coverage and highly accurate reads are required to reach low limits of detection. It’s also ideal for larger solid tumor panels, like our newly introduced Oncomine Tumor Mutation Load Assay for immuno-oncology, large inherited disease panels, as well as exomes and transciptomes. All these applications will benefit from reduced cost per sample as a result of this innovation.

RM: The S5 series includes the S5, S5 Plus and S5 Prime systems. What are the differences between these systems and what role can each system fulfill for your clients? 

AF: The platforms are differentiated on three key parameters: The Ion chips each system is capable of running, the throughput per day, and the speed of analysis of the raw data. The entry-level Ion GeneStudio S5 System is primarily geared for those who are new to next-generation sequencing and is capable of running the Ion 510, 520, 530 and 540 chips. It can handle a single run and data analysis per day using one Ion 540 chip per day.

The mid-tier Ion GeneStudio S5 Plus System is for the more established NGS user who needs additional capabilities.  This platform can run and analyze two Ion 540 chips in a day or one Ion 550 chip.

The Ion GeneStudio S5 Prime System is for the power user who demands the most throughput and shortest time to result. It delivers high level of dynamic range for applications where read depth is important, read lengths of up to 600 base pairs. It is designed for applications requiring long reads to drive more powerful and cost-effective experiments. This system is capable of running two Ion 550 chips per day. 

RM:  You’ve also announced a newly expanded set of your Ion AmpliSeq On-Demand Panels, which users can optimise with the S5 series’ interchangeable chip system. What are these expansions and how will they benefit users?

AF: Ion AmpliSeq on Demand Panels are a customizable content format that has been newly expanded in 2018 with a selection of up to 5,000 genes that have been pre-designed, pre-synthesized and are inventoried by gene. The user can simply select the genes of interest for a particular disease area via Thermo Fisher’s novel Disease Gene Association Database. This is a highly curated set of gene lists that are relevant to particular phenotypes and helps the research save an incredible amount of time they otherwise would spend trawling many other databases and publications to find all genes that might be relevant. The diseases can also be subtyped into many categories with the relevant genes.

Users can then select up to 500 genes that we assemble from inventory very quickly to generate a panel for the researcher. These panels can be ordered in small numbers of reactions - 8, 24, or 96 - that can be quickly updated as genes of interest shift. This capability also dramatically lowers the upfront cost for these large panels, down to $1-3K - depending on format and size. With 5,000 genes in our AmpliSeq On Demand offering, we are now covering just about everything that is relevant today in the inherited disease space.

Andy Felton was speaking to Ruairi Mackenzie, Science Editor for Technology Networks