We lately sat down with Dr. David Smith, Ph.D., one of many audio system on the upcoming Pageant of Genomics California right here in San Diego. Dr. Smith, a professor within the Division of Laboratory Drugs and Pathology, wears many hats on the Mayo Clinic, together with operating a lab the place he works on the characterization of the widespread fragile sites within the genome and on the position that human papillomaviruses play in the improvement of quite a lot of totally different cancers.
AllSeq: Amongst your many roles on the Mayo Clinic, you’re the Chairman of the Know-how Assessment Group for the Middle for Individualized Drugs. Are you able to share with us your perspective on how the genomics market has been changing?
Dr. Smith: For about ten years I was the chairman of the analysis Core Oversight Committee, which was a committee that oversaw the varied research cores at the Mayo Clinic. And it was that that time limit that I really turned knowledgeable not just about genomics but in addition about how the applied sciences themselves have improved. We do have loads of genomics amenities, but there’s additionally mass spectrometry, bioinformatics, circulate cytometry, and issues like that. However about eight or nine years ago I turned the chairman of the know-how evaluation group at a time limit once we truly acquired our Middle for Individualized Drugs up and operating. So the know-how that I’m most serious about, as a result of I feel the know-how that’s going to be probably the most transformative, needs to be genomics-based technologies. And it’s not just the subsequent era sequencing, however I feel a variety of them are centered round that because that’s a know-how that may exchange so many different things. We’re beginning to see that even issues like cytogenetics are going to be replaced by a sequencing-based know-how. Cytogenetics is definitely reworking from classical cytogenetics to array CGH and that seems to be the platform. But in a short time that’s going to rework to sequencing. So my position because the chairman of the know-how assessment group, and I’ve been doing this beautiful a lot since I feel the whole next era sequencing revolution started, is to see the varied producers that produce the platforms for sequencing. However it’s not just sequencing as a result of obviously you could isolate nucleic acids. You want increasingly more robotics for the preparation of the libraries and, very importantly, after you do the sequencing it’s essential to have the required infrastructure to take all that info, assemble it, make some sense out of it. Then you definitely want to be able to translate that again to the clinician, and the last element is you need the required know-how to take all that knowledge and retailer it. So all of that may be a huge a part of the entire element of what sequencing has develop into as we speak.
AllSeq: NGS is beginning to be adopted within the clinic, with NIPT, cancer and rare childhood illnesses being the first examples. The place do you assume we’ll begin seeing NGS adopted next?
Dr. Smith: Wellness. You keep seeing these things now the place, especially now that we have now the Olympics arising, the place they’re going to start out to consider how you need to use most of these applied sciences to raised inform our elite athletes what’s the most effective coaching program. That interprets down (to the overall population) – I’m an extended distance runner – I’ve run loads of marathons. In order that entire group of people definitely are going to need to have this info so you’ll be able to have your training packages centered around your genomics. And I feel that’s going to be an enormous space after which that’s going to translate to the overall inhabitants. We’re type of seeing it already with these exams you can take at house, like 23andMe and issues like that. It’s easy information about your heritage but ultimately it’s going to get to the point the place that info lets you determine what are the most effective coaching packages, what’s the greatest eating regimen, and issues like that. So I feel that may be a big area, however it’s an essential query that you simply ask because I can’t consider an space that gained’t be impacted by this revolution. Proper now we’re seeing – just as you stated – these things starting to be translated into the clinic, but the reality is it’s going to happen in all elements of medical apply. Cancer is an effective first place to start out as a result of it’s a low hanging fruit. We spend a lot money for most cancers remedies that more often than not don’t work. Take a look at the big financial savings we will have if we simply get a bit of intelligent about it. However the actuality is that heart problems, neurodegenerative illness, weight problems, diabetes – throughout the board – is going to be utterly reworked by these technologies over the subsequent couple of years.
AllSeq: How far along the adoption curve do you assume we are for medical next era sequencing?
Dr. Smith: Nicely it’s already being adopted, there’s absolutely no question about it. When you return 5 years in time there was absolutely no subsequent era sequencing as any element of medical apply. And at present, definitely within the Mayo Clinic, however in so many other locations as nicely, increasingly more checks are reworking medical follow. Five years ago I’d say all the molecular genetic checks have been PCR and Sanger sequencing based mostly. They’re beginning to understand how far more powerful subsequent era sequencing is. Why take a look at one gene and then go through that and take a look at another gene the whole diagnostic odyssey when you possibly can simply make a panel of genes, or what I’d advocate, which would be the exome, to take a look at all the things? So I feel it’s undoubtedly being adopted, but the query is, “where are you?” Because in the event you’re at the Mayo Clinic or you’re at any one in every of these very giant places, I feel it’s already occurring. For those who’re a small regional hospital and smaller locations than that, it’s about to be carried out however it hasn’t occurred yet.
AllSeq: What are the most important elements stopping NGS from being extra extensively adopted within the clinic?
Dr. Smith: Properly there are a selection of issues which might be really slowing this thing down. It’s exhausting to say what’s the primary, nevertheless it comes to the top of my record as this general situation about reimbursement. And we definitely really feel it right here, however plenty of places do as properly as a result of they’re doing these exams they usually’re questioning have they got codes for the varied things, or what sort of reimbursement can we get? However that’s just one of the issues. A real significant issue, and Mayo Clinic has it and a lot of different locations do as nicely, is that this know-how isn’t just the acquisition of a sequencing machine. It’s the building of an enormous infrastructure that has the required machines, that has the required experience to run the machines; more importantly, has the required experience to take the info from the machines and make some sense out of it. And eventually, you must have some approach to translate that sensibly with the intention to inform a clinician precisely what to do. You’ll be able to’t ship someone an encyclopedia of variants and say “you figure it out.”
AllSeq: Driving down the cost of sequencing has been the most important push for the NGS market up till now. Do you are feeling this is still the world that needs probably the most improvement, or are different elements turning into extra necessary?
Dr. Smith: There is a need, but there isn’t the out there know-how. Now individuals like Thermo Fisher don’t like to listen to this. Definitely individuals like Pac Bio and Oxford Nanopore don’t, however we stay in an Illumina sequencing world. Illumina utterly and completely dominates the sequencing area. I feel that’s an incredible disservice to the whole effort, because with the absence of competition Illumina is beneath no strain to improve something like output or customer care, and those are necessary issues. The output on these machines is unimaginable in comparison with the place we have been just some years in the past. However over the past yr to two years there hasn’t been any actual dramatic improve in output as a result of Illumina has absolutely no competition. They appear again they usually see no one behind them, they usually might make the false claim that folks don’t want extra sequencing or more output and that’s truly improper. Individuals truly do need extra sequencing. Everybody talks concerning the $1000 genome, and it does value lower than a thousand dollars on the most important Illumina machines to do a genome sequence, however that’s not the complete value of a genome sequence. A genome sequence is how a lot it prices to sequence, to assemble, to interpret, and to store. And should you put all of these issues together, proper now, we’re in all probability in the era of the $5,000 genome, not the $1,000 genome. So, in actuality, truly there’s a want for larger sequencing output. I personally assume the $100 genome is a greater target, and when you get to there, why can’t you could have a $10 genome, as a result of that may truly drive the complete market. And that may also completely rework the character of the sequencing that we do. The truth is, that with the notable exception of NICU (neonatal intensive care models), there’s relatively little entire genome sequencing, clinically. It’s simply an excessive amount of info, it’s too much to assemble, and there’s an excessive amount of problem in figuring out what it means. But if we might have the genome sequenced for less, then I feel the entire market of the small gene panels – the exomes – will absolutely disappear, and that may turn into the best way the genome is characterised.
But there are loads of things that undoubtedly have to be improved. Within the perfect world, in an absolute ultimate world, what can be implausible can be to have machine like what the Pac Bio machine was imagined to be. They claimed ten years ago that would give actually long reads, that it might give really high sequence accuracy, that had large output for a very low worth. But we’re miles away from virtually all of these targets. So what we’re left with is a world where you’re speaking about 100 to 300 base pair sequences, and from the Illumina platform. And what might have actually improved that is a few issues: larger sequence output in order that the precise sequencing prices less. However I feel that proper now the most important thing, and everyone talks about this, is the analytical bottleneck. How do you’re taking that info, how do you translate that info, and do one thing with it?
Partially 2 of our interview we’ll contact on further subjects, comparable to POC and DTC sequencing, focused vs exome vs entire genome, and more.
You’ll be able to catch Dr. Smith at the Pageant of Genomics California, which is being held in San Diego for the primary time. The Pageant can be held from September 19th – 21st and gives free registration for the primary periods. You’ll want to take a look at their BaseCamp for workshop alternatives.