sequencing


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.

Deep Omics Profiler, Mike Snyder, Now Turns to Wearables

Mike Snyder is well known in the genomics community for his iPOP (integrated personal omics profiling) study. Profiling himself with hundreds of thousands of measurements each day over a period of seven years and a group of a hundred others for about three years, he and his team at Stanford have shown that sequencing and other omics data can be used to predict Type II diabetes, cancer, heart problems and other disease. He’s also published numerous papers comparing NGS instruments. Now he is expanding iPOP with a whole new set of tools: over the counter wearable devices.

Though Fitbit’s sales may be down, Mike says wearables are hot. His team has found that there are over 1,000 health related wearable devices on the market today. He predicts that we will all be wearing them, using data that will be centralized onto the "dashboard" of our smart phones to drive our health decisions.

Those who have used wearables have used them mostly as “activity monitors,” and they tire of the devices after about three months. His lab, says Mike, is looking at wearables differently by using them as “health monitors.”

“The power of these devices is that they will measure continuously your basic physiological parameters, and we think that complements the other sorts of data that we’ve been collecting quite nicely. We actually think these devices can be used to tell when you’re getting sick.”

Just as when omics data predicted his own onset of Type II diabetes, Mike says wearables data helped him quickly diagnose his contraction of Lyme disease. The data in the recent two year study also showed when three others were getting sick—their heart rates went way up over baseline.

What about all the wild goose chases and the chance for hypchondria?

“I’m a believer in letting the data tell us what’s going on,” he says. "I didn’t know my blood oxygen level dropped on flights. In hindsight, it makes a lot of sense. And that’s what everyone says, 'it makes a lot of sense.' But most people didn’t know that. This could be a big issue for those with pulmonary illnesses.”

We end with a brief discussion of Mike’s new book: “Genomics and Personalized Medicine: What Everyone Needs to Know."

  

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."

Scientists vs Trump: January 2017 with Nathan and Laura

As we look back at January’s headlines with our two regular commentators, Nathan and Laura, the question becomes: How much should we ignore the fire raging across America to focus on the science?

Speaking of Trump's new immigration order and the very real threat of a "brain drain," Nathan tells of his own personal time doing research in Iran, commending scientists there and the many Iranian scientists here. But he says Iran has already announced they're going to retaliate.

“We might think more about field work scientists who will be worried about retaliation, about being a target of anti-American violence in the field,” says Nathan. "This gets real for people.”

Laura says “the United States has always been the place to come. If we don’t choose to be that place, someone else will. Someone else will be the leader of the scientific world which has been as important to the development of this nation as being leader of the free world.”

We do get to some science, the first human-pig chimera.

And to some cool new sequencing tools. Or just how cool are they? Illumina announced a new line of instruments this month, but what they didn’t say might be the loudest announcement of all. They didn’t mention anything about nanopore sequencing.

We’re Over Halfway There: Baylor's Richard Gibbs on Clinical Genetics

There’s a basic assumption in our field today that has been around for some time. We think of medicine as on a direct and even continuum with science. That discoveries in genomics, for example, will lead directly to breakthroughs in medicine. But the breakthroughs on the medical side have been much more rare to date than those coming from the study of biology and genomics.

Richard Gibbs is the Founder of the renowned Genome Sequencing Center at Baylor College of Medicine. He and his team were one of five worldwide sites contributing to the Human Genome Project (HGP). In today’s interview we find out what the sequencing pioneer has been up to since the days of the HGP and what his take is for how well genetic science is translating into clinical care.

In fact, Richard is willing to put a number on how far we’ve come.

“There’s a trajectory that began just about the time the Human Genome Project was being conceived through to this futuristic image of medical genomics where complete genomes are actually part of medical care,” he says. "That journey is not yet complete. We are somewhere between 50 and 90% there.”

Richard says that the HGP was actually a departure from what was typical in the field of human genetics. That it was a science project done more purely for the sake of science. Most of the history of human genetics research has been practical medical or clinical projects.

One of the areas where Richard’s team has made a big impact is in collaboration with the NHGRI's Center for Mendelian Diseases. The team is also participating heavily with the NIH’s Undiagnosed Disease Network. What is the difference between a Mendelian and a rare disease? What are the center’s solve rates for each of those areas?

We round out the discussion with a look at how Richard and his team get the 'best quality genomes' for their projects, an issue of utmost importance in the clinic.

Luke Timmerman on His New Biography of Lee Hood

There is tons of life science journalism. Our coffee tables and inboxes fill up each week with that quarterly or that daily. We sift through headlines and product advertisements to assess what’s going on in our industry. It’s our job to know. In this age of several-times-per-day newsletters and 24 hrs a day Twitter, we catch what we can.

And occasionally, we come across a carefully written piece or a well done interview, and we take a moment to realize with some awe the history that is being made in our industry.

Occasionally. Which is why a new book out by veteran biotech journalist and the guest of today’s show, Luke Timmerman, is such a rare treat.

Hood is a thrilling ride through the life of the visionary biologist, Lee Hood, told by someone who is not afraid to show the shiny and the not so shiny. From his boyhood in Montana to being chair of the biology department at Caltech where he oversaw the invention of the automated DNA sequencer, to being recruited to Seattle by Microsoft’s Bill Gates, Hood’s journey becomes the perfect vehicle for Timmerman to probe into the messy corners of science and put an intimate, human face on the history of biotech. Covering Hood’s move to the University of Washington as a young Seattle based reporter, Timmerman has known Lee Hood for several years. It's a full scale biography, efficiently and confidently written with an insider's perspective and access. Timmerman says it's an “unofficial biography,” meaning Hood was supportive of the project, but Timmerman had full freedom.

Playing historian has been somewhat of a fantasy for the long time journalist.

"There are things that are happening in the moment which a journalist can call people on, but you don’t really get the whole story. There’s only so much people can say and there are not a whole lot of documents that come available when you’re on deadline. But when you’re a biographer, and you have the luxury of time, and people have moved on, things become a lot less sensitive. People become more willing to talk, and a whole lot of documents become available through the public record.”

Who is this man, Lee Hood, and how has he impacted our industry? In the book, we read of the time when Hood holds a press conference to announce his team has done it—they’ve got an automated DNA sequencer. But, standing at perhaps the pinnacle of his career, Hood forgets to mention the "team" part. It’s a flaw that will go on to haunt what by any measure has been a remarkably successful career.

What impact has the subject made on the author? And what does Timmerman hope for the book?

To round out the interview, we get Timmerman’s thoughts on his new gig, the Timmerman Report, and the recent Sarepta decision by the FDA.

Erica Ramos on Her Pioneering Role as Genetic Counselor for Industry

For the next installment of our series on genetic counseling, we’re joined by Erica Ramos. She’s the president-elect of the National Society of Genetic Counselors and was the second genetic counselor hired at Illumina where she’s been for four years. Illumina now has 15 genetic counselors.

Erica has been a trail blazer throughout her career. Before joining Illumina, she was the first ‘cancer counselor’ in the city of Las Vegas, Nevada. Her time at Illumina has been a prime example of the evolving role of the industry counselor.

“Genetic Counselors are starting to be recognized more and more as experts in bridging gaps between physicians and researchers, patients and physicians, and now even companies and their customers,” she says at the outset of today’s interview.

When asked about the tension between the commercial pressure from her company to sell tests and the actual needs of the patients, Erica says Illumina wants to sell the right tests and she quotes Illumina’s new CEO, Francis de Souza: “sometimes you need to go slow before you can go fast.” Erica says that it’s good for business to engage the genetic counselor early on in product development so that the right product is chosen.

We finish the interview with a preview of the upcoming National Society for Genetic Counselor's annual education conference, Sept 28 to Oct 1 in Seattle, Washington.

A Maniacal Commitment to Science: Peering into Regeneron’s Genetics Center with Jeff Reid

Today we feature a pharma company that has been around for some time but recently getting more media coverage for the impressive scale of their new genetic center. Regeneron Pharmaceuticals, insiders joke, has been an overnight success that took 25 years.

One might think every big pharma company has their own genetic center for internal R & D. But today’s guest, Jeff Reid, Executive Director of Genome Informatics at the Regeneron Genetic Center (RGC), says that actually deep genetic research is often outsourced.

In just two years, the RGC has built an impressive sequencing lab and announced large partnerships with healthcare systems and academic centers that rival major government projects. One such collaboration with Geisinger Health System involves the sequencing of 100,000 genomes. Already, the RGC has sequenced over 100,000 exomes and has plans to sequence 500,000.

“What we’re doing is quite different,” says Jeff. "We are envisioned as a large scale academic genome center embedded in a pharma company."

Jeff says the strategy is to not only go wide with studies of large numbers of patients for the purpose of finding very rare variants, but to go deep as well. Big numbers can be distracting, he points out, saying that some times they get more insight off a small project, such as the treatment of children with a rare genetic disease.

“There are strategies all across the spectrum of project size,” he says.

Set up in an age when compute and data storage are no longer an issue, the RGC has become the first large scale genetic center to be entirely in the cloud. What is the major informatics challenge for Jeff and the center? And what does having such a large scale genome center mean about Regeneron and where we are today with genomic medicine?

Genomics Is Oversubscribed, Says Creator of BLAST

One of the original Celera team that worked on the Human Genome Project, Gene Myers is now setting up the new Center for Systems Biology at the Max Planck Institute of Molecular Cell Biology and Genetics.

However, unlike many others such centers, the main focus of this institute will not be genomics. Rather Myers is going for microscopy.

“Genomics is only about 20% of it,” he says in today’s interview from his office in Dresden, Germany

Myers feels that genomics is overcrowded. He wants to look at the “rest of the stuff” which he finds to be “the most important." Seeing that human genomics was more a matter of scaling after the Humah Genome Project, Myers scientific curiosity led him into microscopy where he seeks to take images of transgenic constructs in the cell and build computer models of basic biology.

"Now that we have reference quality genomes of a number of model organisms, we can do transgenics at scale,” says Myers. "We can take any protein or any promoter and see where it’s being expressed in the cell, and in which cells. And that ability--to basically watch any given protein of interest--has been a huge accelerant to the discovery of biological phenomenon."

With much improved imaging—from better, cheaper cameras to the availability of digital storage—Myers envisions that microscopy will be the breakthrough new platform for biological discovery, similar to what sequencing has been.

“It’s my belief, that if I can build that platform, that people will come and look at transgenic constructs over and over again until we have a very complete atlas of what’s going on in the cells at each point in time,” he says.

What is the biggest challenge to developing such a platform? Myers says the key will be adaptive optics, imaging technology that can adapt for the limitations and aberration of light in the cell.

With 10K Genomes Sequenced, Genomics England in High Gear: Clare Turnbull, Clinical Lead

We’ve heard on the program over the past few years that genomic medicine will probably take off first in a country with a centralized health service. And when the U.K. announced their 100K Genomes Project at the end of 2012 with the creation of Genomics England in 2013, it was certainly a bold visionary move to do just that—to put the entire country on a progressive path toward precision medicine for all.

So with 10K genomes sequenced, how is the project going?

“We’re still early days in the program in delivering it,” says today’s guest, Clare Turnbull, Clinical Lead for the Cancer Program. "Because the National Health Service in England is a single health care provider, it is possible to leverage carrots and sticks to make sure things happen. This gives us a lot more opportunity to effect change than in a more disparate service such as in the U.S.”

What are those carrots and sticks? What new paradigm shifts must take place, and what are the biggest challenges?

Beginning with rare diseases and cancer in this first project, the overall goal, Clare says, is to bring next generation sequencing technologies "full scale in their entirety into our healthcare service, and build all the structures that are necessary to use these types of tests--in particular, whole genomes--as routine investigations in every patient in every hospital within our service.”

Clare says she is a fan of Mendelspod because we provide "a very American perspective" on the same challenges and opportunities.



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