genomic medicine

Invitae and PacBio CEOs Share Details of Clinical Sequencing Partnership

In a joint interview, Sean George, CEO of diagnostics firm, Invitae, and Christian Henry, CEO of sequencing tools company, Pacific Biosciences, say that “it was clear in the first five minutes of a phone call that they shared a vision for doing something big together.”

What comes through the interview is that this partnership is built on a big vision: speeding up the adoption of whole genome sequencing into clinical medicine as the preferred method for genetic testing.

A press release at the beginning of the year announced their multi-year collaboration including the development of a production-scale sequencing platform to process clinical whole genomes at scale. In the release, Sean George said “the collaboration is aimed at developing the technology to make it affordable and accessible to all patients who can benefit from in-depth, full genome information.”

What we get today is an early preview of the new platform from Christian Henry and an exploration into Invitae’s view on clinical whole genome sequencing. Is the market there yet? Will it change Invitae’s business model? Where will long read sequencing be most valuable in diagnostics?

Mid-year, PacBio announced the acquisition of Omniome, a short read sequencing technology. How does that play into the deal?

Catch it all here today as we explore the future of genomic medicine.

Robert Green: Newborn Sequencing Is the Goal Here in the U.S.

"If you go to a scientific meeting, even with the greatest critics, and you ask, how many people in this audience believe that your entire genome will be part of your everyday medical care in fifty years, every person will raise their hand. So the only questions we’re debating are: how do we get there, how soon can we get there, and what evidence base must we have in place before we get there? What’s really exciting to me is getting there sooner rather than later. If we get there 20 years sooner, we are saving thousands of people's lives.”

That’s today’s guest, Robert Green, Professor of Medicine at Harvard Medical School and a physician-scientist who directs the Genomes2People Research Program at Brigham and Women’s Hospital, the Broad Institute, and Ariadne Labs. It's with this program that Robert and his team have led the MedSeq and BabySeq studies.

Robert says when he first announced BabySeq, a study to do whole genome sequencing for thousands of newborns, there was a lot of push back in the community. Is there a built-in tension between his desire to democratize genomic information on the one hand and to do clinical trials on the other? We ask him this and many more questions in a show that pulls back the curtain on the latest efforts to bring whole genome sequencing into the day-to-day practice of medicine.

The Studies Are In—Optical Mapping Can Replace Traditional Cytogenetics Tests

We’re all aware of the way that next gen sequencing has changed many tests in the clinical laboratory. But some testing has held stubbornly resistant to change. This has been the case in cytogenetics, or the analysis of chromosomes. That is now changing thanks to a technology that is making inroads where next gen sequencing could not.

Alex Hoischen, Associate Professor of Genetics at Radboud University Medical Center in the Netherlands, is the lead author of two landmark back-to-back studies out this week demonstrating the power of optical genome mapping (OGM). The studies show 100% concordance of OGM to traditional cytogenetic techniques (karyotyping, FISH, and CNV microarrays) across both constitutional and hematological malignancy applications.

In today’s show, Alex says that the traditional cytogenetic testing hasn’t changed or been replaced by any sequencing approach for roughly 50 years.

“So it’s about time to change that. And in these two studies, we gave the first glimpse that OGM is on track to do so.”

Alex goes into some of the challenges of traditional testing and the benefits that optical mapping brings. It’s a single test replacing various tests. It also can be easily analyzed by lab personnel without the need for intensive bioinformatics resources, as is the case for whole genome sequencing.

The studies point to a change in standard of care in the clinic, but Alex says that optical mapping holds new possibilities for the research lab as well.

When and Why Whole Genome Sequencing Should Be Standard of Care: Stephen Kingsmore of Rady Children’s

There’s an urgency about Stephen Kingsmore. Which is not to say he’s in a rush.

He’s the CEO of the Rady’s Children’s Genomics Institute. He and his team have two world records to their name for the incredible speed of diagnosing a rare disease using whole genome sequencing. The latest is 19.5 hours.

Dr. Kingsmore feels they can even shave time off that. They’re shooting for a new record of somewhere around 12 hours.

"Seriously ill babies don’t have time. They need tests now. Why should whole genome sequencing be different than any other diagnostic test? This is not for intellectual purposes." Says Stephen on today's program.

We’ve heard arguments for whole genome sequencing becoming standard of care before on Mendelspod, but none with this clarity or urgency. The bottom line is this: whole genome sequencing is already standard of care at Rady Children’s, says Stephen, but with an asterisk. The costs are still high, and the team still has work to do to make the argument to payers.

The sequencing center serves hospitals in all four counties of Southern California and is building partnerships around the country. Dr. Kingsmore predicts they will be a model for children's hospitals nationwide.

Genomics England Making Significant Strides in System Built on Trust in NHS

“In an era where we look at these surveys about trust and everything’s going off the cliff, everyone still trusts the NHS. It’s so deep in the British psyche."

That’s today’s guest, Chris Wigley, the CEO of Genomics England, a government run company (a strange concept for us Americans), set up as a sequencing center for the UK’s NHS or National Health Service. The company also does massive bioinformatics work to bring genomics and EHR data together using the latest in machine learning methods. (Note to data scientists drooling over those legendary datasets: Genomics England is hiring.)

What many may not know is that Genomics England has finished the original 100,000 genomes it was set up to sequence and is now shooting for 500,000 genomes by 2024. Just this month the company set up a new platform that is split into two arms, one for diagnostics working with the NHS and one that is research based.

It’s our first interview with a CEO of Genomics England, and it’s a chance to ask everything. One comes away with a very optimistic picture for genomic medicine taking hold in a country where trust in a national healthcare system and rational science are just a given.

90% Go Undiagnosed, Says Geisinger’s Amy Sturm of FH Patients

More than one in two hundred people have an inherited form of heart disease. But most don’t know it.

Often on Mendelspod we talk about cancer genomics, but in the area of cardio, too, genetic testing can save lives.

Amy Sturm is the Director of Genomic Counseling and Screening Program at Geisinger Health Systems. There she has led the effort to return the results of cardio genetic tests to over 1,000 patients.

FH, or familial hypercholesterolemia—Amy says we need to get used to saying it out to spread awareness—is the most common inherited predisposition for heart disease. Over 90% of those with the FH variant go undiagnosed.

What does it mean for one's health if one has this gene? What are Amy’s pioneering studies at Geisinger revealing as they diagnose more and more cases and report results back to patients? How does cascade testing work where family members are notified and sometimes tested? And finally, what are Amy’s thoughts on the new polygenic risk scores that are coming out in the field of cardio genetics?

It’s an area of genetics ripe for its own Anjelina Jolie moment, says Amy.

Ewan Birney on Race, UK Genomics

Our end-of-year special guest is one of the U.K.’s top genomicists, Ewan Birney, Co-Director of the European Bioinformatics Institute at EMBL. He is also the non-Executive Director for Genomics England.  Ewan's perhaps best known for his work with the ENCODE consortium.

We begin by following up with Ewan on a popular blog he co-wrote in October on race and genetics that responds to some of the latest trends on this topic. What does he think of “racial realism? How does he like being called “woke?” But there were issues not covered in the blog: if indeed race is cultural, what are DNA scientists doing talking about it?

We move on to general questions about genomic medicine in the UK. Ewan gives a nuanced answer on whether or not to do BRCA screening and paints a context for genomics which is different than we see in the U.S.

In a year when major genomic medicine companies have faced the chopping block in America—Human Longevity, Arrivale, UBiome— the field seems to be having a rosier time in England.  One of their health ministers just announced plans to sequence all babies at birth--a plan Ewan admits is aspirational, but "a credible aspiration."  Ewan says England and all the Nordic Viking countries enjoy strong support and interest in genomics. And in the U.K., he says, doing and believing in genomics is rooted deep in a tradition of science that goes beyond politics or any current resident of Downing Street.

Did he mean for his recent piece in the Guardian DNA is not our destiny,  it's just a very useful tool to be a correction to over hype? 

"Yes!  I'm afraid there's a very messy middle here.  It's not the case that genomics is going to somehow solve or radically alter medicine.  That's just not the way it works. But it's also not the case that it's useless.  It is a very useful tool.  It's very similar to radiology.  For certain scenarios, it is really transformative.  It's a core part of medicine.  But it's not the case that all of medicine was completely changed by X-rays."

Early Cancer Detection: Is This Company Ahead of Grail?

The great promise of liquid biopsy technology is in early cancer detection. That is, it's the great future promise. Right? This past month at the annual cancer conference, ASCO, we heard about one such flagship company announcing just which technology they were going to use to do it--DNA methylation.

Well . . .it turns out there is a company, Laboratory for Advanced Medicine, that has been using DNA methylation for their liquid biopsy early cancer detection tests for a couple years already. Tests which are for sale now. On their website, they say they are "saving lives by detetecting cancer early." Presenting data for their technology back in 2017, the company offers two liquid biopsy tests commercially: one for liver cancer and the other, a broader test which confirms that a patient has a cancer, either lung, breast, colon or liver.

“This general test has clinical utility because often times the physician and the patient might have a concern about cancer because of symptoms. The physician has done other tests and eliminated other ailments, and the patient and physician have come to a working hypothesis that maybe the patient has a particular type of cancer. And so they do this test with us, and we report back with high accuracy that, yes, they do have a cancer or, no, they do not.”

Richard Brand, the CFO for Laboratory for Advanced Medicine, reviews with Theral the company’s tests, telling of several use cases over the past couple years and previews the tests on the horizon. The company looks to be ahead of the pack in a growing field.

Should Genomic Screening Be Standard of Care? with Adam Buchanan, Geisinger

Those of us watching every shift in the level of adoption of genomic medicine have our eyes closely glued to Geisinger Health System in Pennsylvania.

Adam Buchanan is the Co-Director of Geisinger’s MyCode Genomic Screening and Counseling program, and today we talk to him about the rationale of making genomic screening part of routine medical care.

The MyCode program—which to date includes over 200,000 participants and has returned actionable results to over 1,000 patients—is an "opt-in" program at Geisinger, so it’s not exactly like getting your cholesterol or blood sugar tests which are routine for most of us. But Adam says Geisinger has made it quite “easy” and part of the system.

What exactly is included in the screen, and what genes top the results reports? Are other health systems around the U.S. following Geisinger’s lead? Are there other nations ahead of the U.S. when it comes to genomic screening?

In the middle of the interview, we spend time on population-wide BRCA screening for women 30 and over. Is Adam for it?

At one point, Adam mentions the boom in DTC testing. Is this "self screening", and are health care providers prepared for these patients when they walk in the door?

Laura Hercher on the DTC Genetic Testing Landscape

"DTC is now too big of an arena to put everything in the same bucket.”

This was a line from Laura Hercher, one of our monthly commentators a couple shows back. The statement made its way around Twitter, so we thought we’d have Laura back to the program and ask her to come up with some more buckets.

It turns out it’s not that easy.  Direct-to-consumer genetic testing is a dynamic and complex space in 2019, a mishmash that quite defies easy categorization.

But if anyone can do it, it's Laura.  She's the Director of Research, Human Genetics at Sarah Lawrence College, a fearless genetic counselor. And she hosts our sister podcast, The Beagle Has Landed, devoted to the topic of genetic counseling.

We set up the conversation with a short history of DTC testing and end with a question about whether the consumer is becoming more savvy, more knowledgeable about genetic tests.  Yes, she says, but warns that the disinformation campaigns are becoming equally sophisticated.

With her characteristic cut-the-crap style, it’s Laura Hercher talking the world of DTC testing, past, present, and a little into the future.

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