The Multi-Platform Approach to Clinical Sequencing with Bobby Sebra, Icahn School

Before Bobby Sebra became the Director of Technology Development at the Icahn School of Medicine at Mt Sinai in New York he worked at Pacific Biosciences, helping to develop their single molecule, long read (SMRT) sequencing technology.

In today's interview Bobby says he left PacBio to be free to use all of the available sequencing platforms to develop clinical solutions. At the Icahn School, he has been scaling up the facilities to include Illumina, Ion Torrent, PacBio and BioNano Genomics sequencers, as wells as researching some of the newer platforms such as 10X Genomics, and Oxford Nanopore Technologies. Bobby’s work includes matching these various platforms with the right project, often going back and forth between short read and long read technologies to get an adequate result.

Building on his familiarity with the PacBio system, one of Bobby's primary projects at Icahn is to take PacBio’s new long read technology and develop new clinical applications, such as looking at more polymorphic domains in the human genome at high throughput.

What are his big challenges? Bobby says that a single cell approach is the next important step for clinical sequencing, and he looks forward to a platform which integrates single cell analysis into one workflow. He is also pushing sequencing tool providers to be able to work with lower input, or smaller initial samples.

What clinical projects has Bobby excited, and what is his reaction to recent skepticism about the clinical potential for the study of genomics? Join us for a wide ranging discussion on the latest in clinical sequencing.


The 9 Billion People Problem: Rod Wing on Plant Genomics

By 2050, there will be 9 billion people on the planet. What will they eat?

This is the question that led Rod Wing, Director of the Arizona Genomics Institute, into the field of plant genomics. What has been accomplished so far in the mission to come up with some super green crops?  And how does Rod see anti-GMO sentiment and the recent trend toward gluten free diets factoring in? 

After answering these questions, he dives into a discussion on which sequencing instruments he has used for plant work. Unsurprisingly, Rod prefers the PacBio long reads even though the cost is much higher than with short read technology. Rod refers to most of the genomes done on Illumina sequencers as GAS genomes, or Gene Assembled Space.

“I call them GAS genomes because they’re full of hot hair. They’re not complete genomes,” he says.

Finishing out the show, Rod tells about a new partnership with the Chinese, $9 Billion for 9 Billion People.

Improving the Backbone of Clinical Genomics : Valerie Schneider, NCBI

When President Bill Clinton stood with Francis Collins and Craig Venter in 2001 to announce the sequencing of the genome, the genome wasn’t really done.

So is it done now? And if not, when will it be done? What does ‘done’ even mean? That first human genome sequence that represented the work of Venter and Collins improved each year and became what geneticists refer to as the reference genome. In 2009 the Genome Reference Consortium, a group of various institutions, was set up for the purpose of finishing this reference genome. And every few years a new version is published. The latest goes by the sexy name of GRCh38.

Valerie Schneider, a scientist at the National Center for Biotechnology Information (NCBI), is the leader of the team working on the reference genome. In today’s interview, she tells us about the ongoing work to improve the reference genome, and why it’s important to science and medicine.

Affymetrix CEO, Frank Witney, on Arrays in the Age of Sequencing

Go about anywhere in the life science industry, and you’ll run into someone who once worked at Affymetrix. Since the founding of Affymetrix and the development of what’s come to be known simply as the Affy chip, the company’s history has been intertwined with that of biotech and the genomics revolution. But what has become of the company today?

In the present heyday of DNA sequencing, some have predicted the death of Affy’s chip or microarray, a platform celebrated in it’s time for the ability to see thousands of genes in one assay. But a recent deal with the prenatal diagnostics company, Ariosa, signals that the array is anything but dead.

Today we talk with Affymetrix CEO, Frank Witney, who has engineered a certain comeback for the company. In the Fall of 2013, Affy's stock hit a low point of $3.01 per share. They had just purchased eBioscience for their flow cytometry technology in an effort to diversify. But Affymetrix was dangerously low on cash. Since then, though, the stock price has quadrupled and quarterly earnings are consistently beating analysts' expectations.

What happened? What is the future of arrays? Will they actually come behind sequencing and be the main workhorse for translating genomics into the clinic?

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.

Sponsored by Big3Bio - sign up for  Big3Bio’s free newsletters for daily coverage of the news, events, jobs, and developments in the life science industry.


Cancer Researcher at Mayo Says Illumina Platform Maxing Out, Looks to BGI/Complete

Today we bring you a story which you probably wouldn’t have heard at last week’s AGBT conference at Marcos Island. While PacBio and 10X Genomics were getting most of the buzz at the annual show on all things sequencing, it could be the new BGI/Complete Genomics platform that steals the show later this year, says David Smith, a cancer researcher at the Mayo Clinic.

In his research, David uses sequencing to analyze the connection between the human papillomavirus (HPV) with oropharyngeall cancer.

“A couple decades ago, the incidence of HPV in oropharyngeal cancer was less than 20%. And now at the Mayo Clinic, 80-90% of these cancers are HPV positive,” he says.

Why? A change in sexual practices, David says.

To find out just how HPV causes cancer and integrates into the genome, David is using ‘long read, mate pair’ sequencing. This is a new technology that essentially converts short reads got from such platforms as Illumina’s into long reads. David acknowledges the nice long reads coming from the PacBio machines, but says the cost is still prohibitive. He’s looking for a price that scales into the clinic, and for this, he's most excited about a product that BGI is rolling out later this year, i.e., an already assembled human genome sequencing for $1,000.

We finish the interview with a discussion about how well clinical genomics is being adopted into practice at Mayo.

Myriad Settlements Mark End of an Era: Antoinette Konski on Gene Patents

This past month one of the most successful genetic testing companies, Myriad Genetics, has been settling one gene patent case after another. Also, the FDA has been attempting to regulate some very complicated lab testing. So we figured we better talk to a lawyer about the devil in the details. We’ve chosen Antoinette Konski of the law firm, Foley and Lardner.

Antoinette agrees that the Myriad settlements indicate the end of an era with gene patents. So how is she advising her life science clients in securing IP?

Antoinette is also interested in the regulation of diagnostics. What does she have to say of the FDA’s recent move on LDTs, particularly with regard to next-gen sequencing tests?

David Schwartz on the Future of Sequencing

David Schwartz was focused on long read sequencing and the structural variations of the genome—the big picture—long before the current trend. His lab at the University of Wisconsin at Madison developed optical mapping and posted the first optical map of the human genome several years ago. And last year, they published the first optical map of a cancer genome.

David is the first guest in our second series to focus on long read sequencing. He was interested in structural variation even before the first human genome was published, an endeavor which he says changed the way we do biology.

How does he see sequencing developing?

“Sequencing will be electronic,” he says. “Ultimately we’ll use synthetic pores. Some sort of non-biomolecule based approach will reign supreme.”

With his illustrative history in genetics, we can’t help but ask David a couple of our favorite questions here at Mendelspod--such as, how much wet lab vs. dry lab for the new biologist?

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.

After a Decade on the Sidelines, Gene Myers Back into Sequencing, Excited about Long Reads


Gene Myers , Founding Director, Systems Biology Center, Max Planck Institute Bio and Contact Info

Listen (6:10) What have you been up to since the Celera days?

Listen (4:08) Last decade more about technology than science

Listen (3:53) Wanting to do science not medicine

Listen (4:10) Not many saying it, but short reads have given crappy results

Listen (4:43) Near perfect assemblies now possible

Listen (3:19) Future of sequencing

Gene Myers is an algorithmicist best known for his time at Celera where he developed BLAST, perhaps the most widely used bioinformatics tool ever.

But then Gene got bored with sequencing projects.

“There was this focus on trying to make sequencing the human genome cheaper,” Gene says in today’s interview. "And we knew that eventually technology would win that one. You didn’t have to be much of a visionary to see that.”

Gene argues that it’s been simply a matter of “turning the crank” over the past decade since the first human genome was sequenced. Scientists have been going from organism to organism, and staring at the human genome for genotype-phenotype correlations. Yes, sequencing has gotten much cheaper, and that is important for medicine. But Gene wasn't interested in medicine. He wanted to move on to new science.

So what has Gene been up to? And why is he getting back into sequencing after a decade on the outside?

The answer has to do with long reads.

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

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