microbiome

A one month old baby is admitted to a hospital with fever. This is cause for serious alarm. The child is put on broad spectrum antibiotics. The infected area is drained and a culture run to try to identify the pathogen. The cultures come back negative, the pathogen not identified.

This is what was happening in a case that our guest David Hong, the VP of Medical Affairs at Karius, talks about at the outset of today’s interview. But because Karius uses the patient’s blood and new testing based on next generation sequencing, they are able to discover cell free remnants of the pathogen and identify the organism causing the baby’s infection. This diagnosis then allowed the doctors to change to a targeted treatment, a more narrow antibiotic.

This story exemplifies the revolution going on in the infectious disease space as a result of new sequencing based tests. The folks at Karius call them liquid biopsies for infections. Today David shares with us the kinds of hard-to-diagnosis cases that are coming to them from hospitals around the country. He also explains how better diagnosis is impacting the main issue on the minds of those in infectious disease today: antibiotic resistance.

How quickly can Karius get a new test out to market? How much discovery do they do for new pathogens? And just what are the possibilities here moving forward into 2019?

As an election nears, the question of race and genetics has been front and center. It even prompted ASHG to take the unusual step of making a group wide statement. The three of us agree: scientists should talk more about the race question with non-scientists.

Two papers in Tech Review this month show that the world of people buying cures and disease prevention through gene editing isn’t around the corner, it’s here. Now what about those who can’t afford it? One of the papers was written by our very own Laura Hercher.

For the Halloween special, Nathan talks bugs, as in microbes, connecting many of this past month’s Nobel prizes in science to discoveries about bacteria—including the one in medicine.

It didn’t take long to come up with our lead story for November’s month in review show. Looking at the pictures of the boy in Germany playing soccer after successful treatment of his rare skin disease is just the kind of images we had in mind when we first heard of stem cell therapies.

The bulk of our discussion moves on to the incredible bullish drive of direct to consumer testing this year, sparked by a decrease in sequencing costs and a favorable political climate. However, this month FDA commissioner, Scott Gottlieb, showed his cards on the topic of DTC testing as well as LDTs in general, surprising many of us.

Laura says the FDA announcement reflects a “sea change” in that the FDA plans to regulate not “test by test, but the testers.”

Nathan cautions that this policy will encourage companies who already have their FDA clearance based on some sound diagnostic tests to then “down the line put out a test that is much more speculative, based on shakier science.” He says this will privilege the bigger companies who are already established in the space over small innovative companies.

It’s November’s genomic headlines with Nathan and Laura.

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.

The last time we talked with Chris Mason of Weill Cornell Medical College the Supreme Court had just decided the controversial Myriad gene patent case. How forever ago two years can seem. Since then Chris has swabbed and sequenced the microbiome of New York City and began the project of sequencing in space.

His favorite research this year has been to longitudinally profile the genome, epigenome, transcriptome, metabolome and microbiome of identical twins, one in space and one on earth.

"We see that the gene expression changes dramatically as soon as you get into space, says Chris on today’s show. "What we’re looking for in particular are changes in RNA methylation--which has been related to circadian rhythm--and also RNA processing and stability. Really we’re looking at the epitranscriptomic changes of astronauts.”

Epitranscriptome? What’s that?

The second half of the interview is devoted to Chris’ assessment of the latest sequencing tools. Chris says he’s pleased with Oxford Nanopore’s MinION. Not only has he sequenced what he thinks is the longest continuous read (86 KB) on the MinION, he says the high error rate has come down and the GC bias is much improved. If this geneticist who sees his work as "a duty to the universe" had to choose one sequencer, which would it be?

Guest:

Colleen Cutcliffe, CEO, Whole Biome
Bio and Contact Info

Listen (2:32) Do we know enough about the microbiome yet to commercialize it?

Listen (5:58) The Complete Biome Test

Listen (6:50) A higher resolution platform for developing new diagnostics and therapeutics

Listen (3:12) What are the low hanging fruit?

Listen (2:25) Going forward what is the biggest unknown for you?

There is an intense research effort underway to find out more about the human microbiome. But do we know enough yet to commercialize it?

Whole Biome is one of a handful of new startups in the microbiome space. It was founded by three former employees of PacBio who decided, yes, they knew enough to begin offering a product, the Complete Biome Test.

One of those founders, and the CEO of Whole Biome, Colleen Cutcliffe, joins us to tell their story.

As entrepreneur trainer Steve Blank said here in a recent interview, startup phase is that time period where a company searches for a successful business model. That certainly applies to Whole Biome. Colleen says that early on, the team saw that there was a gap in bacterial strain resolution that they could fill with a tool, meaning they could offer a much clearer picture of a person’s microbial community than what has been available to researchers.

“Before we even began developing that tool,” Colleen says, "we went out and we talked to people who were key opinion leaders in the field and had been thinking about the microbiome and different diseases for a long time. And we said, hey we feel this is a gap. Do you think this is a tool that would be useful? And they all said, that would be a great tool. And if you start a company around that, we’d love to work with you. And we started the company and went back to them and asked would you like to work with us now. And every single one of them is partnered with us.”

Just what will be their business model? And what are the low hanging fruit Colleen and her team are pursuing? She answers these questions and more in today’s interview.

Guest: Mike Snyder, PhD, Director, Center for Genomics & Personalized Medicine, Stanford

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Listen (6:30) What are the important omics other than genomics?

Listen (6:22) Now studying hundreds of millions of markers to get the complete picture

Listen (3:30) How can a patient benefit from this research?

Listen (1:38) What is the biggest research challenge?

Listen (3:23) Other omics already having an impact on cancer treatment

Genomics is often just the beginning to understanding any disease. There are many other biological mechanisms which are part of understanding disease pathways. Dr. Mike Snyder is perhaps the most biologically tracked man in the world. As part of a research project, he is regularly combing through his own biology, looking at over hundreds of millions of biomarkers on an ongoing basis. This includes his DNA, his proteins, his epigenome, and his microbiome among other ‘omes. Dr. Snyder gives an overview of the various omics which come in to play when understanding the complexity of the human body and disease.

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"Rare Disease Horizons: The Hope of New Research and Technology" is underwritten by the Rare Genomics Institute.

Guest:

Mike Hunkapiller, CEO, Pacific Biosciences

Listen (4:58) What is the theme for 2014 at PacBio?

Listen (2:50) Are you working on a clinical sequencer?

Listen (6:55) What are your thoughts on regulation and diagnostics?

Listen (3:12) What was your reaction to the Oxford Nanopore data just released at AGBT?

Listen (6:40) PacBio runs becoming the gold standard in microbial sequencing

Mike Hunkapiller, the CEO of Pacific Biosciences, joins us again this year as part of our annual series on NGS. Last year, Mike stressed the importance of PacBio's SMRT(TM) sequencing to do longer reads than the competition--namely Illumina. He says PacBio will continue to stay focused on further improving read length and accuracy this year as well. In fact, he says that the PacBio technology is becoming "the new gold standard" for microbial sequencing.

What does Mike think of the first data released by Oxford Nanopore recently? And what are PacBio's plans for clinical sequencing? Join us in the second installment of NGS 2014.

Today's Podcast is sponsored by Biotix - Makers of a Better Tip for Next Gen Sequencing. Find out how Biotix is setting a new standard in sample delivery here.

Podcast brought to you by: Ingenuity Variant Analysis - Identify causal variants from human sequencing data in just hours. With Variant Analysis, you can interrogate your variants from multiple biological perspectives, explore different biological hypotheses, and identify the most promising variants for follow up.

Guest:

Mike Snyder, PhD, Director, Stanford Center for Genomics and Personalized Medicine Bio and Contact Info

Chapters: (Advance the marker)

0:42 An update on iPOP

9:02 A model for the clinic?

15:39 How has the project impacted your personal life?

20:46 What is your definition for 'health?'

27:55 Power to the patient

30:11 BONUS: Thoughts on the George Church media flap about cloning Neanderthals

When Mike Snyder gets a cold, the world knows. Hundreds if not thousands of data points change in his body. Snyder, Professor of Genetics at Stanford Medical School, is perhaps the most biologically tracked person on the planet. In our last interview, Mike shared the results of a study that he's calling iPOP, or integrated personal omics profiling. The study achieved recognition around the world for predicting that he had Type 2 Diabetes. At the time he was showing no symptoms. This would not have been caught by any doctor. It was found by tracking his 'omes.' When he went into the clinic to check, his blood glucose level was indeed in disease range, and he immediately went on a strict diet and exercise regime.

In this interview, we follow up with Snyder a year later. He is still tracking his biology, collecting 40,000 data points 20 times in the last 14 months. And he has kept to his strict diet and increased exercise plan. Mike talks about what the study could mean looking forward to using this kind of data in the clinic and also how the study has impacted his personal life. For Mike, health has become a set of data points watched over time. The study has now increased to looking at his microbiome, and ten new subjects are being enrolled for similar tracking. Will the 'Synderome' become the model for omics in the clinic?