Nick Downey on IDT's NGS product development process
Prior to his role as senior product manager for NGS, Nick served as IDT’s applications scientist and a scientific applications specialist, where he executed experimental designs and in-house training, and performed escalated troubleshooting for customers. Downey was previously an assistant professor teaching biology and genetics before joining IDT. Downey has a Bsc. from the University of Salford and a PhD in molecular biology from the University of Iowa. He recently talked about IDT, its products, and his role at the company.
On products designed by real bench scientists:
Well, I mean it's essential, right? It's completely worthless dreaming up some product that you think is wonderful and does all this cool stuff if no one actually cares. Having people who are experts in the field help develop the product–along with insight from customers–allows us to stay grounded in what the real issues are for real scientists, not product managers who sit in an office all day.
How did bench scientists help inform development of Exome v2?
Early on, we had discussions with bioinformaticians and the lab teams over the content of our xGen Exome Research Panel v2 and trying to figure out what the best content was for people. It seems obvious what an exome is, but actually it can be quite a complicated discussion as to what you include or–more importantly, perhaps–don't include in an exome. Getting that perspective on the kinds of questions that would be asked and the kinds of gene types that would be of interest was very important. We ended up putting in a couple of non-coding RNA genes, which is the antithesis of what an exome should be, but so many of our customers are interested in those that we decided that, rather than custom spiking every time, we should put them into the exome. We also put in the TERT promoter, which is important in a lot of cancer studies. We get so many requests for it, it just made sense to put it in up front.
On challenging aspects of the Exome v2 development process:
An exome is huge. There are a lot of dynamics within that. When you have so many things working at the same time, you are trying to control them and sometimes isolate them, so that you can key in and optimize. This can be extremely challenging and what you end up seeing on a gross scale is that as you improve some metrics and other metrics fall by the wayside. It's quite a complicated balancing act to make sure that you get the optimal overall performance.
On rewarding aspects of Exome v2 development process:
Launching the product. (Laughs). You know, it was a year-long effort, with multiple phases facing various challenges. Getting to the end was extremely rewarding but I think also seeing the performance develop as we went through the process was really exciting. We started with our initial design and our initial probe production, and reviewing that and looking for ways to make it better and just seeing it get better was very rewarding, indeed.
Can you talk a little bit about what the process looks like and why it takes a year to work on something like this?
Well, it’s complicated, that's why it takes a long time. We have bioinformaticians, synthesis and formulation scientists, lab scientists, and commercial marketing managers, all working together and sort of dividing and conquering this process. We start with a lot of work on the computer to come up with that design, come up with the list, and compare it to our v1. It's always important to make sure that you're improving – not ruining – something. We had been developing a brand new design tool that was intended to make more even coverage and more efficient sequencing. We were sort of testing it and it took a while. We were trying different design times and we had to make some panels different ways and test those up front to see which was the best way to even do the design.
How do you measure that?
We use the different metrics that are important to scientists: evenness, number of unique molecules in there, efficiency of capture; things like that. You look at those, and again, you might win in one place but lose in another, so you have to make decisions on which is overall the best methodology to move forward. Then you make the initial panel and you test it and you try it in different conditions to make sure that it's not fragile. You look to see if you missed something and then you kind of iterate again to improve on that and then try it in new conditions to stress the system. You do a few cycles of that to make sure that what you're going to launch is going to be robust, then you have to validate that through a V+V – verification and validation – crew and do experiments that can show the power of the product. Then you launch it and everything is fine.
“I think quality matters if the science matters, and the science always matters...”
On when quality matters:
I think quality matters if the science matters, and the science always matters, so quality always matters, it's just that simple. Now, with a stocked item the level to which you can control that quality goes up. We like to turn that dial up as high as we can to ensure the quality is always there because then whoever is on the bench doesn't have to worry about it. They can just pick up that tube or kit and it will work because we've made sure it does.
What do you think those who don’t know much about IDT’s NGS offerings should know?
We're not just an oligo company. We have a lot of innovative ideas and products which are going to help them throughout their workflow, starting with their sample and getting it right before sequencing. We can help in a lot of different ways.
What is it about IDT’s development and manufacturing process that makes our quality superior?
IDT was founded by scientists and it's run by scientists. Science is a core value of the company. I think we were the first company to use ESI-MS – electron-spray ionization mass spectrometry – to make sure that all of our oligos were tested before shipping. Before us, no one tested oligos. They made them and shipped them. We take those standards of quality and we apply them to these more complicated, multi-oligo products like Exome v2 or other capture panels. It infuses us to the point that, now that we're making enzymes and prep kits, it's an assumption that if IDT makes it, quality is going to be present throughout the product.