genomic medicine

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?

 

How to Scale Cancer Genomics, with Marco Marra, UBC

Back in 2009 at the annual AGBT meeting for sequencing, Marco Marra presented one of the first cases of cancer treatment using whole genome sequencing.

We caught up with Marco at his office at the University of British Columbia where he heads the Department of Medical Genetics. Marco also directs the Genome Sciences Center which is part of a very special organization called the BC Cancer Agency.

In 2012 Marco and his team began a pilot project at the agency to scale up their work from just a one off case to more routine treatment. While doing whole genome and whole transcriptome testing is not yet “standard of care” for cancer patients, the scientists and researchers at the agency have the opportunity to sit down with oncologists on a weekly basis and explore its use with several patients at a time.

What are the major questions and challenges Marco has encountered in scaling? How is the regulatory environment for genomic testing in Canada? And which camp does Marco adhere to when it comes to whole genome sequencing: quantity or quality?

Join us as we talk to the number two cited scientist in all of Canada.

Biomarker Panel to Predict Type 1 Diabetes

When we talk precision medicine on Mendelspod, we’re usually talking about oncology. But today we shift our focus to diabetes.

Raghu Mirmira is an MD PhD at Indiana University who is working on a panel of biomarkers that would predict Type 1 diabetes. That’s right. Predict.

Having already found a DNA biomarker candidate which detects dying beta cells using the new technology of digital PCR, Raghu is now working to improve the panel with other metabolites.

Will we some day have a Myriad Genetics for diabetes? Raghu says, yes. But he warns that we must also develop new treatment options to go along with a predictive blood test.

“Before we get to the point where this is a commercially available test, we need to be doing further studies to figure out what’s the outcome of individuals who test in a particular way. And what kind of interventions could improve those outcomes in some way.”

Reference Genome Making Major Strides in Ethnic Diversity, Says Valerie Schneider, NCBI

A couple months back, we reported on a study showing that genetic tests for an inherited heart disorder were more likely to come back with false positive results for black Americans than for whites. The study provoked many in our industry to urge scientists to incorporate more ethnic diversity in their studies. So far, biology has been too Eurocentric—the databases are implicitly racist, they argue.

Perhaps no dataset for human genomics is referenced more than the human reference genome, or the GRCh38. This is the "Rosetta Stone” of genomics used by scientists and clinicians everywhere who are assembling and studying genomes. Valerie Schneider is a scientist at the NCBI who works everyday on the GRCh38. She says major strides--enabled in part by better sequencing technologies--have been made lately to add diversity to the GRCh38 and to create other reference genomes for various populations around the globe.

The populations represented with these new projects include a Han genome, a Puerto Rican, a Yoruban, a Columbian, a Gambian, a Luhya, a Vietnamese, and one or two more Europeans.

“The sequence from these genomes is planned for correcting errors and adding new "alt loci" to the reference genome. But these new assemblies are also intended to stand on their own as complements to the reference,” says Valerie.

Valerie reminds us that it’s still early days in genomics. There’s so much diversity in the human population that her team is not sure whether having a single reference for each of these ethnic groups will be sufficient.

With more reference genomes comes the challenge of how best to compare and visualize them. There is a major need for tools that can show large nests of sequence as opposed to a linear reference, she says in today’s interview.

What is Valerie's take on the term “reference quality genomes”, and how will a better reference genome improve precision medicine?

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.

10 Genomics Questions for the Presidential Candidates

ScienceDebate.org has just released 20 science questions for the presidential contenders.  We thought we'd send in our own list of 10 genomics related questions.  Here they are:

 

1.  Will you get your genome sequenced, and 

   A.  Donald, will you show us what percentage of Neanderthal you have?

   B.  Hillary, will you show us the variants you keep on your private home server?

 

2.  If Obama could be cloned, should his clone be able to run for another term?

 

3.  Which of the following would make the best Moonshot:

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?

FDA’s Liz Mansfield on New NGS Guidances

On July 6th, as part of the President’s Precision Medicine Initiative, the FDA issued two new draft guidances for the oversight of next gen sequencing (NGS) tests. The first guidance is for using NGS testing to diagnose germline diseases. In the second, the FDA lists guidelines for building and using genetic variant databases.

To help us understand just what the guidance is and what led to its release, we’re joined by Liz Mansfield, the Deputy Office Director for Personalized Medicine at the FDA.

It’s unusual for the FDA to issue guidance around a single technology, but Liz says that NGS is “transformative” and is eclipsing so many of the older technologies. The biggest challenge is that NGS is a technology used for discovery and has the power to test for so many things at once.

How does the new NGS guidance relate to the much talked about guidance on LDTs that came out a couple years ago? And does the new guidance represent a more incremental, step by step approach for the FDA in dealing with the explosion of today’s molecular testing field?

“No, it’s not an attempt to break down into smaller bites the issue on LDTs. It’s to address this particular technology, regardless of who the developer is,” says Liz.

The two guidances are for very specific purposes and Liz anticipates further NGS guidances to be issued in the future. For example, guidelines for dealing with somatic mutations rather than germline mutations.

After the Genomes: Season 1

Image source:  HBO.com

Andy: Surprise! The human genome is still as boring as it always was.

Chris: Oh, come on, you didn’t get turned on by that BAM file?

Andy: Hi, I’m Andy. 

Chris: Hi, I’m Chris, and this is “After the Genomes!”

Andy: Each week for the next three weeks, we’ll be looking back on Game of Genomes, an ongoing series at STAT News written by science journalist, Carl Zimmer.




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