Genome Sequencing Clinical Applications: What Will it Take to Make NGS Standard of Care?

Kaitlyn Waters:
Hello everyone and welcome to this podcast from Cambridge Healthtech Institute for the Next Generation Diagnostics Summit, which runs August 15th to the 18th, 2017 in Washington DC. I'm Kaitlyn Waters associate conference producer. We have with us today one of our speakers from the Clinical NGS Assays: Technologies and Validation Conference Dr. Liz Worthey, facility investigator and director of the software development and informatics department at the HudsonAlpha Institute for Biotechnology. Dr. Worthey thank you for joining us today.

Liz Worthey:
Thank you for inviting me.

Kaitlyn Waters:
How has sequencing progressed from when you started in the field to now? What do you think have been some of the most important advances?

Liz Worthey:
I think there's a number of parts to this question, one is the technology to do the sequencing itself. When I started in the field it wasn't actually feasible to sequence persons genome was prohibitively expensive because I'm that old. During my training is when the human genome project came around and finally we were able to have the technological advancements to sequence a person, and also the put the sequencing reads together to get an indication of their genome. Now, of course, we can do what can do what back then took 10 years in a matter of days. The sequencing part, back in the day, it cost originally billions of dollars and then eventually back in maybe 2009 just a few million dollars, and now we can do it for just over $1,000. That's a huge advance in a relatively short period of time, so now we can sequence.

At the same time over that same period there were technological advances that allowed us to do the analysis of that sequencing data much cheaper and much faster. Again if you were talking, even back in 2010 to sequence a person's genome and put that sequence together using informatics would still have taken you many, many months, maybe more than a year. Now we can do much of that work in a matter of minutes, not even hours these days with some of the informatics advances and the computational advances that we've seen. All that together means that we can now sequence people's genomes, we can sequence lots of people's genomes and we can do it fast. We can do it cheaply enough that we can actually use it as a molecular diagnostic test, which is one of the things that we do here at HudsonAlpha.

Kaitlyn Waters:
In the session that you're speaking on, at the Next Generation Diagnostics Summit, is on standardizing NGS testing, what efforts are currently going on at HudsonAlpha in this regard?

Liz Worthey:
We currently offer molecular diagnostic whole genome sequencing, and we offer some other sorts of tests as well, for instance clinical Sanger confirmation. A lot of the work really has been to do the standardization of that process in the lab and that's been in place now for a number of years. We’re also working on standardization of how you deal with that. To sequence data when you transform it into clinical knowledge on the informatics side, and that's really the focus of my group.

Our goal is to not have it be bioinformatician running a bunch of scripts or pipelines in the lab, that is what generates the data that is reviewed by the clinicians to generate the final clinical report. We actually develop tools that standardize everything for you. Everything from the data QC to the language of the report is standardized, and then again the goal there is to make it more quicker, make it more efficient, make it cheaper, and make it less error prone. That's where we do a lot of work at HudsonAlpha in that area.

Kaitlyn Waters:
Definitive diagnosis is incredibly important especially in the cases where a family has been on diagnostic odyssey with little to no answers. Can you tell us more about your efforts in this space?

Liz Worthey:
We know that one in 10 people are affected by disease that's caused by a rare genetic underpinning. This is a huge segment of all societies, it cuts across lots of different specialties. There are rare diseases that affect every organ in your body, so this problem has a huge impact on our health care system. At the same time we know that most individual's who have one of these rare diseases have at least three or four misdiagnosis before they get a diagnosis. Currently very few of them get a diagnosis, if you do even exome testing you get at most a 30 or 35% diagnostic success rate. With genome you get probably a good 20% higher than that.

It often takes these individuals, I think it's on average about seven years, to get a diagnosis, and a third of these individuals die before the age of five. They die without ever having a diagnosis in many cases, so this is the crux of everything that we do at HudsonAlpha for clinical genomics. It's our goal to get as many of those people diagnosed as possible. That's one of the reasons that we do genomes rather than exomes. It's also our goal to not just stop at the diagnosis so in many cases they find out what's wrong with their family member but there isn't that information to say what that means for that individual family member.

On the research side we're spending a lot of time trying to identify things that can modify a person's disease, things that we can find in their genome. It's both the clinical, let's get everyone who has a rare disease diagnosed using genomes. Then it is also the next step beyond that, how can we make it truly a personalized treatment for that person based on their genomic blue print, which is their whole genome sequence.

Kaitlyn Waters:
Finally, what do you think it will take to make whole genome sequencing a standard clinical practice? Also, is this something that you think will come to play for more than just rare diseases?

Liz Worthey:
I think going back to that point, that there are many common diseases that are caused by rare variance. Things like inflammatory bowel disease is relatively common but there's lot's of different types of it, each one relating back to a different genetic underpinning. When we say, rare disease, some of them we would think of them as common diseases. On the question of what would it take to get whole genome sequencing to be standard? Well we know that now the cost structure is such that it is actually cheaper to have your rare disease patients go straight for a genome, than it is to do exomes or to do an exomes and then a reflex to a genome.

That is one of the points that I will be making in presentations that I give. It's not financial, a lot of it is really perception and this is something that a number of folks who do genomes and understand how much better they are for the patient and the clinician are actively working on. We need to get out there and tell people that it's not more difficult to do genome than an exome. You'll get many more, 25% more diagnosis from a genome than an exome and that we really need that information so that we can find new causes of disease that aren't in the protein coding part of genes. This is the task that we and other people have taken upon themselves, it's an education task, and it's also task of reaching out to the clinicians and making sure that they have everything that they need in order to be able to use genomic data for this purpose.

Kaitlyn Waters:
Thank you so much for your time and your insights Dr. Worthey.

Liz Worthey:
Thank you again for inviting me. It's a pleasure.

Kaitlyn Waters:
That was Dr. Liz Worthey from the HudsonAlpha Institute for Biotechnology. She will be speaking at the Clinical NGS Assays: Technologies and Validation Conference, part of the upcoming next Generation Diagnostic Summit, which runs August 15th to the 18th, 2017. I'm Kaitlyn Waters thank you for listening.