long read sequencing


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?

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

Guest:

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.

Guest:

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.

RS Sequencer with Hugh Martin, PacBio

Podcast Sponsor: Singulex- Watch our cardiovascular monitoring programs explained on YouTube

Guest:

Hugh Martin, former CEO, Pacific Biosciences Bio and Contact Info

Listen (1:45) Key events for 2011

Listen (9:05) RS Sequencer and its advantages

Listen (9:04) Disadvantages

Listen (:54) What happened to the stock?

Listen (2:30) Mike Hunkapiller joins team

Listen (6:16) What makes a good CEO?

Listen (2:17) How do you keep good people?

Listen (5:54) Fighting cancer personally

Listen (2:42) Clinical sequencing

Listen (3:50) Company direction

Listen (3:27) CSO Eric Schadt moves to NY

As part of our series, Sequencing and Genomic Medicine, I interviewed Hugh Martin of PacBio at the end of 2011. Personally, Hugh made headlines in 09 when he went public with his diagnosis of multiple myeloma. Previously, he served as CEO of ONI Systems—a high-speed optical telecommunications company he founded in 1998 and took public in 2000 and sold to Ciena in 2002 for $1 billion. Mr Martin led PacBio through an IPO and the commercial launch of their much anticipated RS Sequencer. On Jan 6 of 2012 it was announced that Mike Hunkapiller would step in as the new CEO. We hope to bring Mike to the program soon.




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