Will This New Nano Technology Be the Microarray of Genomic Structural Variation? Barrett Bready, Nabsys

Barrett Bready is back on the program. He’s the CEO of Nabsys, a company with some new technology for genome mapping.

Originally Nabsys had been working to develop nanopore sequencing, but after a recent reboot has become focused on scaling up scientists' ability to read structural genomic information. Barrett compares Nabsys’ new multiplex technology for genome mapping to the improvement of arrays over single nucleotide (SNP) detection.

"When we first started we were using solid state nanopores. And we realized that there were limitations to nanopores. Nanopores don’t multiplex well. If you have two nanopores very close to each other and a DNA molecule goes through nanopore number one, the signal in nanopore number two will be effected. So we developed our proprietary nano-detector that can be multiplexed at really high density.”

With long read sequencing now gone mainstream coupled with a growing interest among genome scientists in structural variation, Barrett says Nabsys has a chance to enter the marketplace competing on price and throughput and will have their instrument ready for beta testing early next year.

George Church on What Comes After CRISPR

George Church joins us today. He’s the Robert Winthrop Professor of . . . . well, he’s George Church. And he confirms that, yes, a movie called “Woolly" is being made about his lab. In the next breath, he reminds us (and himself?) that less than 1% of his press is about the woolly mammoth.

George was honored this year as one of Time Magazine's "Time 100 List", and we’re curious about what topics of conversation come up when he’s with non-scientists. What does he think of Trump (or what he calls “the new politics”)? Is he tempted to join the wave of scientists running for office?

“In China, about 80% of their top government officials have a degree in science or engineering, while in the United States it's closer to 1%,” he deadpans.

We cover some scientific ground today as well. George says CRISPR has been overhyped as the step between Zinc Fingers/Talens and the next gene editing tool. So what is the next CRISPR? And what ever came of his 3-D sequencing?


We Need a Google Maps for Metagenomics, Says Rob Knight, UCSD

When will we see the results of microbiome research in our every day lives? And what will that look like?

Rob Knight joins us for the first time today. He’s a professor at UC San Diego and Director of the Center for Microbiome Innovation. He is well known for co-authoring a paper showing that the microbial populations in the guts of obese mice differentiate from those in lean mice.

In addition to studies on obesity, Rob is also interested in the connections of the gut micriobiome with brain disorders, the possibilities for fecal transplants, and also the impact of microbial communities on drug interactions.

On the tools side we hear a lot about the success of single cell sequencing for human genetics; what impact are these new tools having on metagenomics? And if consent is often a thorny issue for studies in humans, what are the ethical issues studying microbes?

Rob says that in the next five to ten years we will be “taking control over our microbiomes,” meaning that we will be able to measure our microbial communities and use this information to improve our diet or to optimize a therapeutic. The big piece missing for translating microbiome research, he says, is better user interface or apps that would abstract away all the technical information. We need to go from the world of GPS coordinates to using Google Maps, he says.

On Bioinformatics Data Sharing and Collaboration: Andrew Carroll, DNAnexus

What does it take to collaborate in genomics?

A platform, for one thing. Over the past few years bioinformaticians have been speculating about a dominant "go to” site that would serve the software needs of those in genomics. Would it be a private company, a Google of genomics? Or would it be a non profit consortium? Would it be created at the government level?

Today we talk to Andrew Carroll, the VP of Science at DNAnexus, a company which has come about the closest of any to being that community platform. Over a year ago, they won a challenge to host PrecisionFDA, a community platform developed for exploring just how to evaluate and regulate NGS assays.

Beginning as a cloud storage company for genomics back when Amazon was just beginning to look to the sky, DNAnexus then evolved into an iTunes-like platform for various genomics software apps. One bioinformatics software on the platform might be great at variant calling, while others specialize in tertiary analysis.

“From the visibility I have, I estimate around a four to five fold increase year over year in the volume of sequencing," says Andrew. "Bioinformatics has grown to the point that it doesn’t pay to be a jack of all trades. A few years ago a project that was a thousand or ten thousand exome scale was a big deal. These days projects are coming up on hundreds of thousands of exomes, even hundreds of thousands of whole genomes."

DNAnexus’ platform isn’t just about a bunch of bioinformatics apps, it’s also a portal where different kinds of organizations can find each other and collaborate; for example, a healthcare provider and a sequencing center. In addition to PrecisionFDA, DNAnexus has been announcing these partnerships, one after another: Regeneron/Geisiner, Rady Children’s Institute for Genomic Medicine, Stanford Genomics Center. The company hasn’t sat back and waited for customers, but have been cultivating a proactive vision for genomic medicine by helping organizations be as open and collaborative as possible with their data.

"The work that we do through our partners actually tells the best story," says Andrew.

Green Light for DTC, Blood Mammograms, and Ancient DNA: April 2017 with Nathan and Laura

For genomics nerds, April 2017 will be remembered as the date when the FDA adopted a more open policy towards 23andMe and direct-to-consumer (DTC) genetic testing. What does this decision mean, and just where is the FDA drawing the line? A genetic counselor herself, Laura found the decision “head turning.”

“There’s lots of reasons why some genetic counselors are not going to be thrilled to deal with everyone’s 23andMe results,” she says.

For the “cool new studies” section of today’s show, Laura is excited about a research project announced by Grail, a spinoff from Illumina working on a pan cancer screening test. And Nathan points out that the trend for researchers to look back at ancient DNA sharpened this month with two new studies that not only open up the possibilities for historians and archeologists but also have relevance to human health longterm.

“We’re getting much better at doing it,” he says. “So look for more of this ancient meta genomics where we can find little fragments of DNA outside of cells but intact in sites like soil. They’re very diverse, but we're starting to figure out really what was going on at a place some time in the past."

We finish with a couple stories that are giving pause to researchers working on gene therapy and immunotherapy.

It’s commentators Nathan Pearson and Laura Hercher joining Theral to talk genomics for April.

In-Situ Sequencing, CRISPR Patents, and Racist Milk Drinkers: February 2017 with Nathan and Laura

Commentators Nathan Pearson and Laura Hercher join us to look back on February’s genomics headlines.

Beginning this time with science, Nathan says we should be expecting great things from new in-situ sequencing. Laura found it encouraging that the National Academy of Sciences shifted to be more in support of genome editing. Theral asks what life forms are left to sequence for the Earth BioGenome Project?

Then it’s back to politics. Are the departure of Liz Mansfield from the FDA and Matt Might from the White House the beginning of a brain drain from government agencies in the new administration? We finish with some stories about racism that might fit under the heading “family genomics and black history month."

By Changing a Basic Lab Step, Acoustic Liquid Transfer Having a Broad Impact

Freeman Dyson famously said, “the great advances in science usually result from new tools rather than from new doctrine.”

Today we talk with Mark Fischer-Colbrie, CEO of Labcyte, a company which has made some waves--literally-- in the life sciences by changing a very fundamental laboratory procedure: liquid transfer. For some years now, Labcyte has been selling machines that move liquid around with sound. By eliminating the need for pipette tips and other “solid” surfaces, the machines guarantee much more precision.

“Science demands precision and in ever-increasing amounts,” says Mark at the outset of today’s interview.

Acting like a rifle shooting liquid straight up, the new acoustic technology has made inroads into most life science applications. Mark talks about the Finnish Institute for Molecular Medicine (FIMM) using the new technology to do truly personalized medicine, by ex-vivo screening of cancer patient cells against hundreds of available drugs. There is often precious little sample to work with, and the errors from traditional pipetting might mean the difference of life or death. The machine is also used widely by the pharma and synthetic biology communities for its ability to reduce costs.

“Imagine saving four months on a single drug discovery cycle,” says Mark.

Recently, Astra Zeneca has integrated acoustic technology into mass spectrometry, showing the potential to immediately upgrade other tools which have been around for some time.

Should everyone change over to acoustic dispensing?

Many Biologists Today Don’t Have Enough Computer Science to Use the Databases

Moray Campbell was for all intents and purposes an accomplished and successful cancer biologist at the renowned Roswell Park Cancer Center. Then one day he woke up and realized he was becoming irrelevant. He was a traditionally trained wet lab biologist who was getting left behind by computer science. Any scientist must keep up with their field, but this was different. A few conferences and journals--reading the news everyday was not going to be enough. Facing reality, Moray enrolled in a bioinformatics masters program at Johns Hopkins.

That was in 2013.

"Biology is genomics. And genomics is basically computer science,” says Moray at the outset of today’s program. “In 2013 I would have said I look at the epigenetics of prostate cancer. Now I say that I look at the epigenomics of prostate cancer. I’ve become genomically literate."

What was it like for Moray to go back to school mid-career with teachers and homework and finals? Did he doubt his decision when the going got tough? Is it harder for biologists to learn coding or coders to learn biology?

Moray is now finished with his degree and in the process learned that as a discipline, we're still struggling with how to teach genomics to biologists.

He gives the example of datasets such as TCGA that many biologists today don’t even know how to use.

“These data are there. And they’re being used very deeply,” he says. "But I suspect by quite a restricted community. If you don’t even know how to download a file, how are you going to be able to analyze it?"

It's been a dramatic transition for Moray. Looking back now he says, "biology is dead; long live biology."

Cardiologists Love Genomics: Euan Ashley, Stanford

Euan Ashley is one of the big names in genomic medicine that has been missing from our guest list. We’re happy to correct that today.

In 2010, he led the team who did the first clinical interpretation of a human genome--that of his Stanford colleague, Steve Quake. Since then Euan, an MD PhD, has been driving to make the use of new genomic tools and discoveries a routine part of medicine at Stanford, particularly in his own discipline of cardiology.

A regular speaker on the conference circuit, Euan titles his talks, "Genomic Medicine Is Here."

"There were these one off examples of great stories that captured everyone’s imagination,” he says at the outset "but somewhere in there, what happened is it just became routine. And we started sending exome and genome sequences on patients and using that information to help find a cause, and in some cases, treatment for their condition. We were all waiting for it to happen, but it just happened under our noses.”

At the same time, Euan acknowledges that he “loses sleep at night” over “dark corners of the genome.” What are these dark corners? What recent findings were made by new long read sequencing? How has genomics impacted cardiology?

We begin with the question, if genomic medicine is here, why are there still so many skeptics?

Join us in our first interview with one of the few jazz saxophonists in our field, someone who knew he wanted to be a doctor at age four but wasn’t inspired by science--that is, until a high school teacher handed him a copy of Richard Dawkins' “The Selfish Gene” after class.

People Told Us It Was Impossible: UCSC’s Mark Akeson on Nanopore Sequencing

Mark Akeson has been working on nanopore sequencing at UC Santa Cruz’s biophysics lab for twenty years. Up until the past few years with the launch of Oxford Nanopore’s sequencers, that work was mostly the methodical toil of the quiet inventor.

Today it is quite ordinary to see a sequencer the size of your wallet being taken out into the field for DNA work. But for years, the naysayers dominated.

“Back in the day, the skeptics outnumbered the proponents 99 to 1,” Mark says in today’s show.

In his beginning-of-the-year blog, NIH Director, Francis Collins, called nanopore sequencing one of the four breakthroughs of 2016. And the NIH deserves some credit.   Mark says they were constant in their funding and belief in the technology.

With the success of nanopore sequencing technology has come legal battles to secure the IP.   Both Illumina and PacBio have sued Oxford Nanopore—the Illumina suit is now settled. And at the end of last month, Akeson’s lab (meaning the University of California) sued Genia, claiming that they owned the patents for Genia’s technology.  Genia was founded in 2009 and we have interviewed them several times since 2011.

“There's the old adage about once something succeeds, there’s all sorts of people who claim to have invented it,” says Mark.  

So what’s next for Mark? Is he on board the “long read train?” How much more can sequencing improve?


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