long read sequencing


Knowing More about What We Don’t Know: John McPherson on Cancer Genomics

More than with any other major disease, the understanding and treatment of cancer is being transformed by genomics. And these are early days.

John McPherson has been involved in sequencing since the original Human Genome Project. He now directs the Genome Technologies Program at the Ontario Institute for Cancer Research. John chaired a panel on cancer genomics at the recent AGBT, or Advances in Genome Biology and Technology conference, and shares his thoughts on this year's meeting.

Like many others, John is excited about the new possibilities gained by long read sequencing, particularly in showing structural variations of various cancers.

We ask John which platforms he likes, and most importantly--in this day with increasing sequencing instrument options--how he decides how much to spend on sequencing to answer a specific question.

"Our goal is to be as accurate as we can," he says. "For single nucleotide variants (SNPs), we see about a 93-95% verification rate. And we’re pretty happy with that. The question becomes how many samples you do, and not what you do to a sample. Depending what question you’re asking, the number of samples affects your power overall.”

John works in Ontario. We ask him about the state of clinical genomics in Canada, a country with a single payer system.

Gene & Tonic: Disruption in Sequencing, Scientist Politicians, Some Cool Synbio

Join Theral for a quick wrap-up of the week's biotech news:

The biggest news this week has been the flow of stories coming from last week’s AGBT conference held in Florida. This is the annual all out party for the all out darling of our industry, the sequencing space. Like a debutante ball, it’s where anybody who’s anybody comes out and does their curtsy to society.

This year’s debut favorite was no doubt 10X Genomics. It turns out they can almost turn water into wine. Well, almost. What they do is turn short reads into long reads, piggybacking on Illumina’s technology. Have you been following our series on the rise of long read sequencing? It turns out that scientists just decided that they want to actually see the whole genome. Hence the use of long reads.

Illumina has reigned king in sequencing for several years, but their platform is based on short reads. We heard from one of our guests on the program this week that Illumina’s dominance is vulnerable. David Smith at the Mayo Clinic says their platform is about maxed out. Instead he looks for some big stuff from BGI.

Huh? BGI? Isn’t that just Illumina’s platform? Well no. He’s talking about Complete Genomics. Remember them? They were at one time a debut darling then got sold to BGI for a song and a dance. (Every debut is followed by a depression, isn’t it?) But we heard this week that Complete’s still got some juice. David Smith says they’ll be coming out with an assembled human genome for $1,000 come June. That’s an assembled genome.

But this is unofficial. BGI/Complete were not saying anything at AGBT. According to all accounts, the biggest presence at the conference was PacBio. They held this workshop with an incredible lineup of scientific superstars. Temporarily the IQ in the state of Florida rose to the national average.

Craig Venter was there. We heard PacBio flew him in on a private jet with a private security detail.

I mean. Wow. Treatment like the President of the United States.

In fact, I’m going to ask why doesn’t Venter just run for president in 2016? Right, why can’t we have a scientist president? Scientists and technologists are basically in control of the planet anyway. Why not get some on Capitol Hill and recognize them for who they already are.

We found out this week that Harold Varmus is stepping down from the NCI. Why doesn’t he run for a higher office? Why do scientists give up at that level?

Did you see the Science Magazine article this week about the one lone physicist in congress. Bill Foster of Illinois. The news was that he is joining the science committee in the House of Representatives. Wait--there is a scientist committee in congress? So who else is on it then? The lone physicist congressman was quoted in the article:

“There are good conversations to be had on both sides of the aisle. But it’s important that those be fact-based.”

D’ya think?

We asked George Church of Harvard why he doesn’t run for the senate. He looks very senatorial, right? He wrote back and said that if he wanted to hang out with a bunch of Neanderthals, he prefer they be of his own make.

No, he didn’t really say that. We made that up.

But speaking of synthetic biology projects, one of our guests this week is making color changing flowers. You can see it on video. These flowers literally change to another color while you’re watching them. Isn’t it just amazing what mankind can do when we get bored? Next thing you know, we’ll be bringing back smallpox, polio and the measles to the U.S. Because living in the age of vaccines just hasn’t been fun enough.

And that’s Gene & Tonic for Friday March 6th. Stay tuned next week when we’ll continue our conversation on long reads with a researcher from the Ontario Institute for Cancer Research. We’ll also be talking about arrays in this age of sequencing in an exclusive interview with the CEO of Affymetrix, Frank Witney.

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Test Driving Genomic Medicine: Thomas Quertermous, Stanford

Guest:

Thomas Quertermous, Director of Research, Division of Cardiovascular Medicine, Stanford University Bio and Contact Info

Listen (7:45) Close, but not quite there

Listen (5:34) How good are the commercial bioinformatics providers?

Listen (8:19) The challenge of education

Listen (5:12) Genetics and heart disease

Listen (2:55) Where do you put the price for whole genome interpretation?

Listen (2:32) Are long reads a big deal?

Thomas Quertermous co-chairs a pretty spectacular committee at Stanford. Called the Dean’s Panel on Clinical Genomic Testing, the committee makes the call on which genetic tests are ready for prime time in the clinic. Thomas joins us to launch our new series, Genomic Medicine Today: Where Are We?

The goal of this series is to find out just what practical progress we’ve made in commercializing whole genome sequencing. What are the success cases? How many are there really? What are the obstacles and keys to progress?

TQ, as he's known in the industry, recently co-authored a paper published in the Journal of the American Medical Association (JAMA) that provided a snapshot of just where we’re at today with genomic medicine. The conclusion? We’re close, but not quite there.

The key to clinical whole genome sequencing, he suggests, is to come to it with the question of "what you hope to learn from the adventure."

“I think it’s good if you start with a goal and try to stick to that goal rather than create an all encompassing analysis of the genome," he says in today’s interview.

As for challenges, TQ says that we need better healthcare informatics solutions, and always, better education at the provider level.

What are his thoughts on the leading commercial solutions for whole genome interpretation, and does it really cost $100,000? What does TQ think about the rise of long read sequencing led by PacBio this past year?

Join us as we begin a new series probing the front lines of clinical genomics.

Podcast brought to you by: Omicia - Offering end-to-end genome interpretation and reporting solutions to help diagnostic labs and research institutions unlock the potential of individualized medicine.

The Progress of Clinical Genomics in Sweden with Ulf Gyllensten

Guest:

Ulf Gyllensten, Professor, Department of Immunology, Genetics, and Pathology, Uppsala University, Sweden Bio and Contact Info

Listen (4:24) What are your goals at the National Genomics Infrastructure?

Listen (4:42) PacBio revolutionizing HLA typing

Listen (4:01) Getting the word about long reads out to clinicians

Listen (3:17) What would you like to see from sequencing companies in the future?

Listen (8:03) An update on clinical genomics in Sweden

Listen (5:02) The Road Show

For our final show in the series on long read sequencing, we move to Sweden and talk to Ulf Gyllensten, Co-Director of the National Genomics Infrastructure.

Ulf and his team use all the major sequencing platforms, and one of their jobs at the NGI is to compare the platforms. In today’s interview, he tells of the goals at the NGI and how new long read technology from PacBio is opening up new applications.

Some of these applications are clinical, and Ulf gives an update on clinical genomics in Sweden where regulation and privacy concerns are much more straight forward than they are here in the U.S.

Podcast brought to you by: Pacific Biosciences - providers of long read sequencing solutions based on their Single Molecule Real Time technology.

Test Driving Illumina's X Ten with Shawn Baker, AllSeq

Guest:

Shawn Baker, CSO, AllSeq Bio and Contact Info

Listen (5:27) Taking the X Ten for a test drive

Listen (6:56) What is the latest price for a whole human genome sequence through Allseq?

Listen (3:05) Illumina's bold move into clinical space

Listen (7:17) NGS story of the year: X Ten or long reads?

Listen (7:24) Latest from Oxford Nanopore and Genia

In January, Illumina made headlines by announcing that their new HiSeq X Ten sequencers now can deliver the $,1000 genome.

“Sort of “. . . says today’s guest, Shawn Baker, the co-founder and CSO of AllSeq. They are an online marketplace connecting providers and users of sequencing. AllSeq offers their users a way to get access to a close to $1,000 genome without having to shell out the big capital.

Recently AllSeq teamed up with one of their providers, the Garvan Institute, an early adopter of the X 10 system, along with the bioinformatics platform, DNAnexus, to do a test drive on the expensive but impressive new devices. They are offering a free look at the data here.

Having Shawn on the program is always a chance to get an overall perspective on the sequencing space. What are his thoughts on the emerging importance of PacBio's long reads? And what's the latest from Oxford Nanopore and Genia Technologies?

Podcast brought to you by: Chempetitive Group - "We love science. We love marketing. We love the idea of combining the two to make great things happen for your marketing communications."

Has the Race to the $1,000 Genome Proceeded at the Expense of Quality? New Series on The Rise of Long Read Sequencing

According to a 2010 article in Bio-IT World, the term $1,000 Genome has been around since 2001.  The University of Wisconsin’s David Schwartz claims to have coined the term at an NHGRI retreat during a breakout session.  Whatever its origin, the $1,000 Genome soon became the target for the rapid development of next-gen sequencing (NGS).

After Buyout, Cliff Reid, Complete Genomics Stay on Track

Podcast brought to you by: Ingenuity Variant Analysis - Identify causal variants from human sequencing data in just hours.

Guests:

Cliff Reid, PhD, CEO, Complete Genomics Bio and Contact Info

Listen (3:32) Audience questions about Long Fragment Read technology

Listen (3:53) From 200 to 5000 people

Listen (4:11) How do you respond to national security questions?

Listen (4:39) Genomic tests will be commodotized like computers

Listen (7:38) Thoughts on bioinformatics

Listen (2:44) Conversation of bioethics being changed by Facebook generation

Listen (2:51) Future role at the company

In March of 2006, Cliff Reid teamed up with Rade Drmanac and John Curson and founded a company to commercialize a new DNA sequencing platform. But rather than make another sequencing tool and sell it, the company, known as Complete Genomics, would use a different model. They would be devoted entirely to sequencing human genomes as a service. In February of 2009 the company announced its first human genome. By the end of '09, Complete had sequenced 50 human genomes. And in the 3rd quarter of 2010, they sequenced and analyzed 300 human genomes. In 2012, BGI, or Beijing Genomics Institute, offered to purchase Complete for $117 million, and after clearing regulatory hurdles in the US and China, on March 18th the acquisition of Complete was complete.

CEO, Cliff Reid, joins us today in one of his first interviews after the buyout sounding as enthusiastic and on track as he did in our earlier interview. He admits there's a joke in his family that "the fourth time is the charm," because he was involved with two other startups that were ahead of their time. Cliff will be staying on as CEO with the same vision of advancing clinical genome sequencing. He says the company will be commercializing their LFR or Long Fragment Read technology, and he answers questions from our audience about when and how. Acknowledging that the company didn't have the staying power to get to the clinical market and were squeezed out of the research market by an unforeseen preference for exome sequencing, Cliff is still bullish that the price of genome tests must continue to come down further to make a difference in healthcare around the world.

2013 'State of NGS' with Shawn Baker, BlueSEQ

Podcast brought to you by: Ingenuity Variant Analysis - Identify causal variants from human sequencing data in just hours.

. . . and by Biotix - makers of A BETTER TIP(TM) for Next Gen Sequencing

Guest:

Shawn Baker, CSO, BlueSEQ Bio and Contact Info

Listen (9:29) The year of steady boring progress

Listen (4:44) PacBio has made impressive improvements

Listen (3:47) Nabsys and the gospel of long reads

Listen (4:29) Moleculo technology still unknown

Listen (4:55) Has sequencing technology reached a more stable plateau?

Listen (2:13) Illumina has a history of bumping heads with their customers

Formerly with Illumina, Shawn Baker is now CSO of BlueSEQ and a consultant on matters to do with next gen sequencing. He joins us for the second time to give an overview of the NGS industry. We caught up with Shawn just after AGBT where the industry players announce their latest and greatest.

Baker calls 2013 "the year of steady boring progress." Noting that there were not any huge breakthroughs, he says in fact there were some big promises made last year which have not been delivered on. However there has been progress, most notably by the steady improvements made to the PacBio system, and by the emergence into the field of companies such as BioNano Genomics and Nabsys focused on long read technology. What is Shawn's take on the gospel of long reads? And what does he think of the new Illumina/Moleculo technology? Join us for the State of NGS 2013.

Nabsys Close to Product Launch: CEO, Barrett Bready

Podcast brought to you by: Ingenuity Variant Analysis - Identify causal variants from human sequencing data in just hours.

. . . and by Biotix - makers of A BETTER TIP(TM) for Next Gen Sequencing

Guest:

Barrett Bready , CEO, Nabsys Bio and Contact Info

Listen (5:44) Will Nabsys be the first to deliver a nanotech based sequencer?

Listen (7:11) Timeline for product release

Listen (2:13) Renewed focus on long reads

Listen (1:57) Thoughts on Moleculo

If there was a darling at this year's AGBT (and the genomics community has come to expect them), the spot would go to Nabsys, who presented their "positional" sequencer that employs nano detectors in a single-molecule approach. In today's interview, Nabsys CEO, Barrett Bready says he was surprised by the response to his new sequencer at the show and said many of those watching the machine work in real time expressed their desire to purchase the machine. Bready, who strikes me as quite modest even though he's sitting on what could be a game changer, says the company will be ready to commercially launch the product for around $50K in the second half of the year.

Bready talks about a major theme of last week's AGBT meeting and a theme we've been focusing on in this series: a renewed focus on long reads. "A relatively small number of us have been talking about the importance of structural variation and context and the ability to do de novo assembly for a while, and I think its now becoming mainstream in the genomics community. It's like real estate, location matters," he says in the interview.

Have We Been Missing the Big Picture in NGS? Erik Holmlin, CEO, BioNano Genomics

Podcast brought to you by: Ingenuity Variant Analysis - Identify causal variants from human sequencing data in just hours.

Guest:

Erik Holmlin, PhD, CEO, BioNano Genomics Bio and Contact Info

Listen (4:46) There is a lot of information lost with short read technology

Listen (5:06) What is an example of the practical impact of structural perspective?

Listen (8:49) Is it possible to have one platform that is good at short read and structural view?

Listen (11:28) From the clinic back to the tools space to persue the bottleneck

Listen (1:40) Thoughts on Moleculo

With all the advancement in next gen sequencing, have we actually been missing something important? Erik Holmlin thinks so. He's the CEO of BioNano Genomics, and he's left a career delivering diagnostics to the clinic to go back into the tools space and develop a new sequencing technology that would give a better structural view of the human genome. "I believe, broadly speaking, that the bottleneck in genomic medicine is unique and clinically significant genomic content. And the reason we don't have that is we don't have all the tools that scientists need. So I'm trying to develop those tools." That is a bold statement. In today's interview, I ask Holmlin if there is a new NGS Gospel to be spread?



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