long read sequencing

Test Driving Genomic Medicine: Thomas Quertermous, Stanford


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


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


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.


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


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


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.


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?

SEQUENCING: Hunkapiller Chips Away at PacBio's 'Perception Issue'

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


Mike Hunkapiller, PhD, CEO, Pacific Biosciences Bio and Contact Info

Chapters: (Advance the marker)

0:53 How does PacBio fit into the overall sequencing picture at the beginning of 2013?

5:45 Limitations of 2nd generation technology

14:18 What has been your goal as CEO?

20:11 Are there plans for a less expensive technology?

26:25 How would you characterize yourself?

30:31 Has PacBio already spent their reputation?

35:30 Thoughts on Ion Torrent, Oxford Nanopore, and Illumina

Is PacBio a solid company that has been victim of an over-hyped industry?

Sequencing has become a high stakes, treacherous business. No other technology in the life science industry has seen the same hype. For many years, including those when the human genome was first sequenced, Sanger type or first generation automated sequencing remained relatively unchanged. Applied BioSystems was the leader, providing their 3700 Automated Sequencer to both groups which worked on the first human genome. Then Illumina bought Solexa in 2006 and everything changed. This was next generation sequencing, and since then the pace of development has gone on a steep improvement curve that everyone is familiar with. Slides showing this curve sit in most industry leaders' slide decks.

Where is the technology in 2013? Last year began with the announcement from the two major players, Life Tech and Illumina, that they'd be sequencing a human genome in a day. But according to Shawn Baker, CSO at BlueSEQ and regular guest at Mendelspod, neither delivered. Baker maintains a neutral database on the various sequencing technologies over at www.blueseq.com.

"They haven't quite reached the 'genome in a day' goal. Illumina is closer with a 36 hour run from the HiSeq 2500 generating enough material. Life will have to wait until the PII chip, slated to launch sometime in the first half of 2013, is able to generate at least 50Gb per run," he said in an email. (Stay tuned for an upcoming overview with Shawn.)

At the beginning of 2012 Roche made a move on Illumina, showing how important the technology has become to drug development. In our 2012 series on sequencing, we featured some of the promising newcomers touting 3rd generation technology. PacBio had just launched their RS system. And we heard from some of the nanotechnology companies promising disruption soon, Genia and Nabsys.

Yet this year so far, we have heard none of the hype we have come to expect. Is the news this year that there is no news? Has the technology reached a more stable zone? To explore this question and find out what's happening in this exciting sub-industry, we'll be featuring another series on sequencing. And we launch it today with PacBio, and their new CEO, Mike Hunkapiller.

Mike has had an incredible view of the sequencing business. He was president of Applied Bio during their heyday with the 3700. He recruited Craig Venter and helped found Celera, the private enterprise which co-announced the sequencing of the human genome. He's been a partner at Alloy Ventures, the VC firm which funded Applied Bio and PacBio. He has seen and heard the hype that surrounded PacBio as they secured funding of $370 million, went public with a market valuation of $800 million and promised a 15 minute genome for $1,000 by 2013. And he saw them launch their system, burn through $500 million, and see their stock devalue quarter after quarter. So it's 2013 and where is the technology?

Mike's experience and steady, methodical approach shines through in this interview. He has a way of cutting through the hype as he talks about the limits of 2nd generation, or what he calls 'short read' technology and establishes an important place for PacBio and their success with long reads. I've heard several times this last year that PacBio had serious problems, among them accuracy. And this for a machine that cost more than any of the other technologies. Industry experts have wondered aloud if PacBio would suffer the fate of a meteor burning out.

I came away from the interview with much less skepticism. Hunkapiller says that PacBio has suffered from some "perception issues," and this year they've proved that their "accuracy is actually extremely good." His approach has been to focus on their existing customers and make sure they had success with the technology. The company has upgraded their software and their chemistry. Last month their stock shot up 46% on news that UC Davis would use the RS for the 100K Genome Project. What about Oxford Nanopore and their new technology? What about Illumina's recent investment in longer read technology? Hunkapiller answers these questions with great aplomb and is quite convincing that PacBio is certainly not out of the picture.

Note: The following correction has been made to this article. Originally it was stated that Illumina and Life Tech had both delivered on their claim to be able to sequence a human genome in one day, if not at the price they predicted. In fact, neither has delivered on the promise.

Positional Sequencing: Barrett Bready of NABsys

Podcast Sponsor: DNAnexus- Unlocking the potential of DNA-based medicine and biotechnology with a collaborative and scalable DNA data management and analysis technology platform.


Barett Bready, CEO, NABsys Bio and Contact Info

Listen (3:59) What brings you to DNA Sequencing?

Listen (3:33) Positional sequencing

Listen (4:13) Advantages

Listen (2:05) Is sequencing by hybridization sloppy?

Listen (4:20) How far along is the technology?

Listen (1:47) Market positioning?

Listen (4:25) Why Rhode Island?

Listen (4:00) What drives you personally?

Dr. Barret Bready is the CEO of NABsys, a company pursuing faster, higher quality sequencing technology for use in research and clinical care. The company is presenting their data for the first time at AGBT this year. Since joining NABsys, Barrett has been named one of the top "30 under 30" in New England by The Journal of New England Technology and 2011 Innovator of the Year in the state of Rhode Island.

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