DNA sequencing


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.

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.

The Snyderome

Podcast brought to you by: Ingenuity Variant Analysis - Identify causal variants from human sequencing data in just hours. With Variant Analysis, you can interrogate your variants from multiple biological perspectives, explore different biological hypotheses, and identify the most promising variants for follow up.

Guest:

Mike Snyder, PhD, Director, Stanford Center for Genomics and Personalized Medicine Bio and Contact Info

Chapters: (Advance the marker)

0:42 An update on iPOP

9:02 A model for the clinic?

15:39 How has the project impacted your personal life?

20:46 What is your definition for 'health?'

27:55 Power to the patient

30:11 BONUS: Thoughts on the George Church media flap about cloning Neanderthals

When Mike Snyder gets a cold, the world knows. Hundreds if not thousands of data points change in his body. Snyder, Professor of Genetics at Stanford Medical School, is perhaps the most biologically tracked person on the planet. In our last interview, Mike shared the results of a study that he's calling iPOP, or integrated personal omics profiling. The study achieved recognition around the world for predicting that he had Type 2 Diabetes. At the time he was showing no symptoms. This would not have been caught by any doctor. It was found by tracking his 'omes.' When he went into the clinic to check, his blood glucose level was indeed in disease range, and he immediately went on a strict diet and exercise regime.

In this interview, we follow up with Snyder a year later. He is still tracking his biology, collecting 40,000 data points 20 times in the last 14 months. And he has kept to his strict diet and increased exercise plan. Mike talks about what the study could mean looking forward to using this kind of data in the clinic and also how the study has impacted his personal life. For Mike, health has become a set of data points watched over time. The study has now increased to looking at his microbiome, and ten new subjects are being enrolled for similar tracking. Will the 'Synderome' become the model for omics in the clinic?

Lee Hood: Salesman for Science, Part II

Podcast brought to you by the upcoming Personalized Medicine World Conference taking place in Mountain View, CA, January 28-29. Over 100 speakers in three tracks will discuss how best to navigate the changing landscape of personalized medicine.

Guest:

Dr. Lee Hood, Founder, Institute for Systems Biology Bio and Contact Info

Listen (11:04) Pharma's core problem - good at making drugs, poor at finding drug targets

Listen (2:11) Are scientists the world's new rulers?

Listen (2:35) The Montana Factor

Listen (3:38) NIH funds Small Science

Today's interview covers some very broad topics and comes in two parts. It could only be done with an industry Titan, a scientist, an entrepreneur, a visionary, and a great salesman. Our guest is Lee Hood, founder of the Institute for Systems Biology.

I've been looking forward to having Dr. Hood to the program since we started, and delighted that it worked out now. During the interview, you'll hear Lee's take on some of our common topics here at Mendelspod. First, I explore Lee's foresight in bringing together biology and engineering. This has proved a beautiful marriage and led to Lee's direct involvement in the design of the automated DNA sequencer. This discussion has further implications for Dr. Hood, as this was the first of several paradigm shifts he's been part of. In fact, paradigm shifts have been a study of his and a theme throughout his career. He says an early mentor at Caltech urged him to "be on the cutting edge."

It's not easy being at the cutting edge, breaking paradigms. Dr. Hood had to leave the university system to found his dream environment for research and education, the Institute for Systems Biology. Dr. Hood talks about that step as a defining moment for him and his ideas. He explains the core ideas on which the Institute is founded and relates them to the broader picture of healthcare. Rather than healthcare, he predicts we'll call it the wellness industry.

Another favorite topic at Mendelspod is the role of the scientist in society. More and more,scientific discoveries and technology dictate the course of human life. When asked whether scientists are the world's new rulers, Dr. Hood tells the anecdote of his brief flirtation with the idea of running for senator in Montana.

It's obvious that Lee's home state played an important role in his life. He attributes his confidence to the independence he felt at the behest of his mother and the opportunity to hike and experience the wilderness. He was exposed to an academic setting in highschool and recalls that often academic pursuits were combined with trips into the wild.

Finally I ask Dr. Hood a question that came from the audience about whether tax dollars should fund bad science. His answer is nuanced and thoughtful. He warns of being to cynical of 'bad science' or non-reproducable research. He goes on to make the point that there is Big Science and Small Science. He calls the NIH a funder of small science.

Dr. Hood's experience is vast. He's a great thinker. He's an innovator, concerned with a big vision. He's also been able to sell his vision, achieving remarkable success. We've split the interview into two because I just couldn't bring myself to stop Dr. Hood after 30 minutes. A listen through to both shows brings one very close to understanding what our industry is all about.

(Editor's Note: On 12/21/12, Dr. Hood was awarded a National Medal of Science.)

Lee Hood: Salesman for Science, Part I

Podcast brought to you by the upcoming Personalized Medicine World Conference taking place in Mountain View, CA, January 28-29. Over 100 speakers in three tracks will discuss how best to navigate the changing landscape of personalized medicine.

Guest:

Dr. Lee Hood, Founder, Institute for Systems Biology Bio and Contact Info

Listen (2:08) Where did you learn to be such a great salesman for science?

Listen (11:45) What led you to be at the confluence of disparate disciplines?

Listen (4:15) Emancipation from the university system

Listen (8:40) At the end of 2012 how far along are we on the journey to P4 Medicine?

Today's interview covers some very broad topics and comes in two parts. It could only be done with an industry Titan, a scientist, an entrepreneur, a visionary, and a great salesman. Our guest is Lee Hood, founder of the Institute for Systems Biology.

I've been looking forward to having Dr. Hood to the program since we started, and delighted that it worked out now. During the interview, you'll hear Lee's take on some of our common topics here at Mendelspod. First, I explore Lee's foresight in bringing together biology and engineering. This has proved a beautiful marriage and led to Lee's direct involvement in the design of the automated DNA sequencer. This discussion has further implications for Dr. Hood, as this was the first of several paradigm shifts he's been part of. In fact, paradigm shifts have been a study of his and a theme throughout his career. He says an early mentor at Caltech urged him to "be on the cutting edge."

It's not easy being at the cutting edge, breaking paradigms. Dr. Hood had to leave the university system to found his dream environment for research and education, the Institute for Systems Biology. Dr. Hood talks about that step as a defining moment for him and his ideas. He explains the core ideas on which the Institute is founded and relates them to the broader picture of healthcare. Rather than healthcare, he predicts we'll call it the wellness industry.

Another favorite topic at Mendelspod is the role of the scientist in society. More and more,scientific discoveries and technology dictate the course of human life. When asked whether scientists are the world's new rulers, Dr. Hood tells the anecdote of his brief flirtation with the idea of running for senator in Montana.

It's obvious that Lee's home state played an important role in his life. He attributes his confidence to the independence he felt at the behest of his mother and the opportunity to hike and experience the wilderness. He was exposed to an academic setting in highschool and recalls that often academic pursuits were combined with trips into the wild.

Finally I ask Dr. Hood a question that came from the audience about whether tax dollars should fund bad science. His answer is nuanced and thoughtful. He warns of being to cynical of 'bad science' or non-reproducable research. He goes on to make the point that there is Big Science and Small Science. He calls the NIH a funder of small science.

Dr. Hood's experience is vast. He's a great thinker. He's an innovator, concerned with a big vision. He's also been able to sell his vision, achieving remarkable success. We've split the interview into two because I just couldn't bring myself to stop Dr. Hood after 30 minutes. A listen through to both shows brings one very close to understanding what our industry is all about.

(Editor's Note: On 12/21/12, Dr. Hood was awarded a National Medal of Science.)

The Cinderella of Genomics with Peter Leigh, Microsonic Systems

Podcast brought to you by: Genia Technologies - Makers of integrated circuits for "Last Gen" DNA sequencing. Biology . . . meet the integrated circuit.

Guests:

Peter Leigh, CEO, Microsonic Systems Bio and contact Info

Vibhu Vivek, Co-Founder, Microsonic Systems Bio and contact Info

Chapters: (Advance the marker)

0:47 Sample Prep - the Cinderella of Genomics

10:10 The big market for genomics will be the clinic

12:00 A linguist learns the language of genomics

17:11 High tech and bio just learning to talk to each other

22:47 Healthcare - the macro picture

BONUS:

30:50 An accidental invention

This week at ASHG 2012 in San Francisco, Microsonic Systems is launching their first product, a high-throughput sample prep system for NGS. We talked with CEO, Peter Leigh, about the system which makes use of an accidental discovery made by co-founder, Vibhu Vivek, when he was a grad student at the University of Hawaii (see bonus section at the end). Peter is an illustrative speaker who has had a long career in the life sciences. He talks of the coming revolution of genomic medicine, saying that the new technologies such as whole genome sequencing are going to do for the 21st century what antibiotics did for the 20th century. His company's focus is sample prep, a laborious process that must be carried out before sequencing, but which doesn't get much attention. In one study, Peter says, they reduced the time it takes to prepare NGS libraries from 10 days down to 1 and 1/2 days. He calls sample prep the Cinderella of Genomics.

Speeding Data Transfer with Dawei Lin, UC Davis

Podcast Sponsor: Ingenuity - iReport, the fastest and most accurate way to get biological meaning from your expression data. www.ingenuity.com/get iReport/

Guest:

Dawei Lin, PhD, Director of the Bioinformatics Core at UC Davis Genome Center Bio and Contact Info

Chapters: (Advance the marker)

0:50 Set up first bioinformatics server in China

3:15 From 26 hrs to 30 seconds: a new high speed connection with China

11:52 Training the next generation of bioinformaticians

25:47 Empowering the masses to understand their own biological data

30:02 BGI and genomics in China

35:15 Know thyself

37:43 EXTRA: Molecular modeling with legos

Dawei Lin set up the first bioinformatics server in China back in 1995. And things have come full circle this past summer, as he was involved in setting up a new high speed connection between China and the Genome Center at UC Davis where he is Director of the Bioinformatics Core. Dawei worked with BGI to set up the connection. We ask him about the company and about genomics in China.

It's Dawei's passion to know himself that brought him to working with biological data.

Google Invests in Bioinformatics: Andreas Sundquist, DNAnexus

Podcast Sponsor: Appistry- Delivering the most cost-effective and the highest quality analytics for your NGS data. Jumpstart your analysis with runs beginning at just $99. Appistry, complex analytics made simple. Guest: Andreas Sundquist, CEO, DNAnexus Bio and Contact Info Listen (9:28) An instant online genomics data center Listen (2:31) Moving bioinformaticians to more interesting work Listen (3:49) From exomes to whole genomes Listen (5:38) Using the cloud Listen (4:35) Mirror of SRA Listen (6:00) Google's investment and the future of bioinformatics Listen (6:12) Is there something in the water at Stanford that creates entrepreneurs? Listen (2:50) Recruiting engineers in Silicon Valley Listen (1:31) Are you the next Sergey Brin? Andreas Sundquist is here to talk about his exciting new company. He’s the CEO and co-founder of DNAnexus, a company receiving a fair amount of buzz since catching a chunk of cash from Google Ventures and TPG Biotech. The company offers cloud based storage and analysis of next-gen sequencing data. Receiving his Ph D in computer science from Stanford, Andreas has published methods for whole-genome mammalian assembly, metagenomics, and population genetics. Andreas talks about his company platform and looks to a time when everyone will have their genome sequenced.




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