sequencing

At the beginning of the year, we were all holding our breath for the future of PacBio. And by all, I mean all. It seems everyone has been rooting for this sequencing technology company.

And why? It’s simple. Pretty much everyone is in agreement that they have the highest quality reads on the market.

So why was their future in question? This could have been asked of many famous companies at one time or another. Apple computer faced their dark days. Disney overcame initial failure. A company’s success in the market does not always align perfectly with the quality of their product. There are other variables.

PacBio at the end of this year is a different company. They have raised two rounds of financing. They have released their Sequel IIe, and they have a new CEO, Christian Henry. From August to November, their stock tripled in price. So what happened? And what is Christian’s new vision for the company?

The main takeaway today is that Christian believes in PacBio’s existing core story: long reads will take science, medicine, and the world to new heights. He thinks this story has been undersold and plans to change that.

We speak directly with the Oracle today. It's Keith Robison, blogger at Omics Omics. Your All Knowingness, we ask, what has happened in the world of sequencing technology this year?

“The companies may need a mulligan,” he quips and laughs.

But then, maybe, not. It turns out the great Pandemic has driven sequencing technology in its own way. There’s been an explosion of sequencing based diagnostics. That trend was already happening, but the pace was mightily booted along. And all of the technologies have been involved—some new entrants as well--used for their own strengths, to track the powerful virus and all its speeding variations.

We take the flagships one by one, from 10X to the small Genapsys, asking the Oracle in the end whether there is any more room for a shakeup in this mature space. We finish with an impressive story of clinical sequencing for rare disease diagnosis at a world record speed. Oh, Oracle, tell us the future.

23andMe lays off over 100 employees. Illumina comes to the JP Morgan empty-handed. Has Precision Medicine seen it’s heyday already? Or are we gearing up for another wave of innovation? Nathan and Laura are again ready for the tough questions of genomics.

We begin with the current spat between genetic counselors and the ACMG. Like, . . . huh?

Two years ago Veritas Genetics began offering whole genome sequencing for a thousand dollars. It was a significant milestone—and still is!—not only for what it means about the company providing the genomes but also what it means about the demand for such a product.

Today we talk to Rodrigo Martinez, the Chief Marketing and Design Officer at Veritas and co-author of a recent blog, Next in The Genomics Revolution: The Era of the Social Genome. The blog puts the current offer of whole genome sequencing into the larger context of the history of genomics, compares the availability of the whole genome to that of the personal computer, and anticipates how interacting with our genomic data may begin to shape our lives.

We have two core questions for Rodrigo: What does a whole genome mean to Veritas? And why should one order a whole genome test?

Rodrigo argues that the time of having single one-off genetic tests or even panels of tests has been superseded. Why not get a whole genome test at the same low price, open an online account with all of our genomic information, and have it all there ready for any future interaction?

Veritas offers their product to physicians and to consumers, giving us another perfect chance to continue our ongoing discussion here on the program about the blurring of DTC borders.

It’s our first interview with someone from Veritas. And it’s a lively and long one.  Rodrigo is a deep diver and never short of breath or ideas.  Enjoy.

Today we engage in a rare discussion between a startup founder who is going beyond sequencing and working directly with cancer patient cells in 3D cultures and with one of his customers, the husband of a cancer patient.

Meet Christian Regenbrecht, the CEO of CPO or Cellular Phenomics and Oncology based in Berlin, Germany and Janos Flosser, a fund manager who invests in technology from Copenhagen, Denmark.

Today’s show is not only special for the fact that we have a researcher/entrepreneur sitting down directly with a patient for the interview, but also for a bold new approach to cancer genomics. Christian is not shy with his attitude about how we must shift our thinking toward oncology.

“Sequencing alone has proved remarkably unhelpful. And the belief that sequencing your DNA is going to extend your life is a cruel illusion,” says Christian at the outset of the interview.

So just what is Christian up to at CPO? How did Janos, a fund manager in another country, find Christian? And is this the new face of cancer treatment?

Sequencing goes to the world of infectious disease.

Building on the work with cell free DNA in prenatal diagnostics and cancer genomics, the team out of Steve Quake’s lab that brought us Moleculo has now launched a new company in infectious disease called Karius. In today’s interview, Karius CEO and co-founder, Mickey Kertesz, recalls the day four years ago when a clinician urgently contacted he and his team with an infected patient that could not be diagnosed by any traditional method. The team took on the case, and though the patient died within a couple days--Mickey recalls the Saturday when the team heard—they went on working on the diagnosis.

“We were very focused and went on fixing the software as if not wanting to believe what we heard.”

After a week the team did arrive at a diagnosis which was confirmed by the autopsy. That patient became patient zero, and the event turned Mickey again into an entrepreneur.

"This was not just cool research, this needs to go quickly into patient and clinician hands,” he thought.

Today Karius is an active company, selling their tests to hospitals around the country, working first on the most difficult cases.

Will these diagnostic tests by sequencing replace the traditional blood tests some day?

“Oh yeah. In a few years, this will be the first line of defense," Mickey says.

"We like to refer to it as consumer initiated, but physician supervised,” says Eric Schadt today when asked if his new test is direct-to-consumer.

Eric is the Dean for Precision Medicine at the Icahn School of Medicine at Mount Sinai in New York and since 2016 has served as CEO of Sema4, a spinoff that he founded out of the Mount Sinai Health System. Sema4 launched a newborn screening panel, Sema4 Natalis, in February of this year covering over 190 disorders.

With 400 people already employed, Sema4 is based largely on genetic testing, data science, bioinformatics, and software development teams that were built up at Mount Sinai prior to the spinout. New panels will be marketed directly to parents around the country, many of whom have already bought other prenatal screening tests from Sema4.

From 2011 to 2017, Eric served as the Founding Director of the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai. He says he founded Sema4 to achieve a greater scale than could be had within a single hospital system. For him and Sema4, the end game is to "partner with" tens of millions of patients for ongoing studies. He calls it his "growth hack" strategy.

The Natalis panel is a practical place to start. Many of the additional rare childhood disorders that expand the panel beyond the conventional heel prick testing of 30-50 disorders are the result of new research and the latest technology and are a no brainer. This will bring some uniformity across states. And the new testing can be done from a cheek swab rather than the more invasive heel prick.

Still, some argue, Sema4 Natalis really amounts to doing research on parents. For the panel includes cancer risk tests as well.

Does Eric plan to do any follow up studies with parents? Mount Sinai is the sole owner of Sema4. Has any other major healthcare provider made a play similar to this?

Sequencing geeks are fresh off the trail from AGBT, and it’s time for our annual look at the sequencing tools space. This year we sit down with the longtime Omics! Omics! blogger, Keith Robison, who not only can answer all your questions about the topic, he even knows which sequencer you’re using right now, and in which department.

Keith jauntily runs through the Big 3--Illumina, Pac-Bio, and Oxford Nanopore--and has a few odds and ends to say about the "niche developers."

We finish by asking Keith what new trends and new instruments he's looking at. He says his son is a senior in high school where Keith has offered to go in and demonstrate the MinIon nanopore sequencer.

"Imagine if the next generation of kids all learns sequencing on this little device. It starts becoming a practical reality where kids in high school--even middle school--learn sequencing and then learn data analysis."

The Flongle Generation, anyone?