Eric Schadt on Long Read Sequencing and Clinical Genomics


Eric Schadt, Professor & Chair Genetics and Genomic Sciences, Director Icahn Institute for Genomics and Multiscale Biology Bio and Contact Info

Listen (5:01) Getting buy-in from a few lead doctors

Listen (5:24) Do you see shift toward long read sequencing?

Listen (6:35) Scaling up for the clinic

Listen (6:03) PacBio leading on quality

Listen (4:07) The genome fractal? Using math in biology

Three years ago, Eric Schadt left the sequencing company, Pacific Biosciences, as their CSO to go be guru of genomic medicine at Mt Sinai in New York City. Backed with terrific funding and leadership, Eric has the resources to be in the vanguard of translating our latest understanding of genomics into real world benefits for patients.

Today he updates us on his work at Mt Sinai, detailing his strategy and the obstacles that he faces. He then weighs in on the rising importance of long read sequencing, not just for microbial research, but for practical human genomics. Eric comments here on the journey of PacBio from a company that was overhyped and under delivering to one that is setting the mark for quality in human genome sequencing today.

“It’s very exciting to see the quality of the PacBio data,” he says. “The utility is just beyond compare, whether you're assembling a bacterial genome de novo, or looking at structural features in the fragile X region of the [human] genome, or looking at methylation simultaneously. ”

Eric has a Ph D in biomathematics. We end by discussing how math will help in deciphering biology.

“We don’t know the language yet of biology. So we’re trying to learn how to write the book without really understanding all the words or knowing how to string the words together into sentences," he says at the conclusion of the interview.

Podcast brought to you by: Pacific Biosciences - providers of long read sequencing solutions based on their Single Molecule Real Time technology.

Major Sequencing Projects Should Be Done with Long Reads, Says Dan Geraghty


Dan Geraghty, Researcher, Fred Hutchinson Cancer Center; CEO, Scisco Genetics Bio and Contact Info

Listen (4:43) Unable so far to find causal linkages in MHC region of the genome

Listen (4:43) Illumina vs. PacBio

Listen (9:27) Major sequencing projects should be done with long reads

Listen (9:32) Is the message about long reads getting out there?

Listen (3:15) What projects will you pursue with long read technology?

Dan Geraghty has a message for anyone looking for genetic causes of disease.

A researcher at the Fred Hutchinson Cancer Center, Dan has been working at characterizing the difficult region of the genome known as MHC, or major histocompatibility complex. This region controls a major part of the immune system and is linked with many common diseases. Until now, Dan says, researchers have so far been unable to find causal linkages to common diseases, such as diabetes, celiac disease, and rheumatoid arthritis in the MHC region because they haven't been able to look at long enough pieces of DNA.

Unlike with Mendelian diseases where a single mutation is linked directly to the disease, the regions in the MHC that are linked to disease often include long "flanking" sequences which play a part. Until now, to get a complete look at a long genetic region, researchers have used Illumina's short read technology and then had a lot of data analysis and finishing work to do. First of all, that finishing takes hours and hours. And secondly it doesn't give an accurate picture.

"The finishing is really prohibitive for a modest research effort," says Dan.

Enter new long read technology. Recently Dan worked with PacBio where he was able to get 40kb read lengths. Contrast that with the 300bp reads of the Illumina technology. There's just no comparison, he says. And the error rate for the long reads: one in a million.

"This is really high quality data," Dan says of the PacBio reads. "This is the kind of zero error rate where you can compare your cases and controls and easily validate them and have high confidence that what you're seeing is accurate."

What does this mean for genomic research going forward? Take the 1,000 Genome Project of the NHGRI. Shouldn't researchers be using long reads to get the most accurate data possible?

And just what projects is Dan pursuing with what he calls the "breakthrough" technology?

"We're hot on the trail," he says. "We basically can see the entire picture. We're not looking under a lamppost for the keys. It's daylight, and we can see the whole neighborhood. So we're gonna find the keys."

Podcast brought to you by: Pacific Biosciences - providers of long read sequencing solutions based on their Single Molecule Real Time technology.

Test Driving Illumina's X Ten with Shawn Baker, AllSeq


Shawn Baker, CSO, AllSeq Bio and Contact Info

Listen (5:27) Taking the X Ten for a test drive

Listen (6:56) What is the latest price for a whole human genome sequence through Allseq?

Listen (3:05) Illumina's bold move into clinical space

Listen (7:17) NGS story of the year: X Ten or long reads?

Listen (7:24) Latest from Oxford Nanopore and Genia

In January, Illumina made headlines by announcing that their new HiSeq X Ten sequencers now can deliver the $,1000 genome.

“Sort of “. . . says today’s guest, Shawn Baker, the co-founder and CSO of AllSeq. They are an online marketplace connecting providers and users of sequencing. AllSeq offers their users a way to get access to a close to $1,000 genome without having to shell out the big capital.

Recently AllSeq teamed up with one of their providers, the Garvan Institute, an early adopter of the X 10 system, along with the bioinformatics platform, DNAnexus, to do a test drive on the expensive but impressive new devices. They are offering a free look at the data here.

Having Shawn on the program is always a chance to get an overall perspective on the sequencing space. What are his thoughts on the emerging importance of PacBio's long reads? And what's the latest from Oxford Nanopore and Genia Technologies?

Podcast brought to you by: Chempetitive Group - "We love science. We love marketing. We love the idea of combining the two to make great things happen for your marketing communications."

Has the Race to the $1,000 Genome Proceeded at the Expense of Quality? New Series on The Rise of Long Read Sequencing

According to a 2010 article in Bio-IT World, the term $1,000 Genome has been around since 2001.  The University of Wisconsin’s David Schwartz claims to have coined the term at an NHGRI retreat during a breakout session.  Whatever its origin, the $1,000 Genome soon became the target for the rapid development of next-gen sequencing (NGS).

Pre-Leukemic Stem Cells with Liran Shlush

Guest: Liran Shlush, Researcher, Princess Margaret Cancer Center

Bio and Contact Info

Listen (4:44) Preleukemic stem cells

Listen (7:42) Implications for AML therapy and diagnosis

Listen (2:21) Implications for other cancers

Listen (6:14) Importance of population genetics tools

One of the common topics on our show these days is how researchers can ask better questions. It takes being master at science, but also being connected with patients and their health problems.

Today's guest, Liran Shlush, a cancer researcher at Princess Margaret Cancer Center in Toronto, solved this by being one of those rare physician-scientists. And it's paying off big time.

In February, Liran and a group from the lab of John Dick at the University of Toronto published a major finding into the biology of acute myeloid leukemia (AML). In today's interview, Liran tells us about the discovery of what he terms "pre-leukemic" stem cells. These mutant stem cells go on to form cancerous cells. When AML patients are treated with chemo, the cancerous cells are killed, but the mutant stem cells are still there and can cause recurrence. The finding holds a lot of promise for both treatment, earlier diagnosis, and new screening for AML and perhaps other cancers as well.

Liran was a post doc at the time of the discovery. He tells of his journey from Israel to John Dick's lab in Canada and the lessons along the way. What led him to ask the right questions?

"The scientific lesson I learned--and I was lucky to learn it early in my career--" he says, "is that nothing in biology makes sense except in the light of evolution."

Podcast Sponsor: Integrated DNA Technologies - Introducing the evolution of NGS capture panels

Clinical Genomics Takes Hold in Iowa: Colleen Campbell, IIHG


Colleen Campbell, Assistant Director, University of Iowa - Iowa Institute for Human Genetics

Bio and Contact Info

Listen (2:35) How are you implementing genomic medicine?

Listen (3:17) Pharmacogenetic pilot with CYP219

Listen (8:24) How are you educating physicians?

Listen (2:32) Which patients are getting their exomes sequenced?

Listen (5:55) What are you doing with secondary and incidental findings?

Listen (1:30) Technical challenges?

Listen (3:33) History of IIHG

Today we take you to the front lines of clinical genomics.

Colleen Campbell is the assistant director at the Iowa Institute of Human Genetics (IIHG), a statewide resource devoted to understanding the extent and meaning of human DNA sequence variation. In March of this year, the IIHG at the University of Iowa began offering whole exome sequencing as well as some pharmacogenomic testing.

In today's interview, Colleen shares with us some practical stories outlining just how the IIHG is bringing genomics into the clinic. How did she and her colleagues go about deciding which pharmacogenomic tests to offer, and how are they dealing with the issue of incidental findings? As both a geneticist and a genetic counselor, Colleen offers a comprehensive, behind the scenes view on a story that is unfolding around the world.

At Mendelspod, we hear a lot about the challenge of educating clinicians on genomics. This has been a key area of focus for Colleen and her colleagues. The genomics team is engaging not only doctors but also nurses and the general community in new ways that could be a model for other clinics.

"Groups who are trying to implement these these kinds of tests need to think about educating the entire healthcare team," she says. "It's really important to educate everyone, from the person who greets the patient at the front desk to the nurses, the physicians, the genetic counselors, and the pharmacists--really anyone who's going to interact with the patient."

We end with a brief discussion about how the IIGH came about, and what are the next moves for Colleen and her team.

Podcast Sponsor: Integrated DNA Technologies - Introducing the evolution of NGS capture panels

Window on the Life Science Industry: A Conversation with Trey Martin, IDT


Martin Trey, COO, Integrated DNA Technologies

Bio and Contact Info

Listen (4:32) The oligo factory

Listen (3:30) How have you stayed relevant in the age of sequencing?

Listen (3:39) A breakthrough in oligo length

Listen (7:18) A window on the industry

Listen (4:12) Thoughts on synbio

DNA. It’s at the core of biology and the life science industry. Integrated DNA Technologies, or IDT has been making DNA for the industry for twenty five years.

Mendelspod has been working for some time now to persuade someone from IDT to come on the program and tell us about their history--how they began, why they're in Coralville, Iowa, and what important trends they're observing.

Beginning a new series entitled Beyond the Oligo, we’re joined by IDT’s Chief Operating Officer, Trey Martin, for a wide ranging discussion about the company beginnings and their unique perspective on a rapidly changing industry.

Further episodes of this series will feature some of IDT's customers-from clinical genomics to synthetic biology-who are using DNA to pioneer dramatic new advances in human health and the way we are moving forward as a species.

Podcast brought to you by: Chempetitive Group - "We love science. We love marketing. We love the idea of combining the two to make great things happen for your marketing communications."

They're LDPs not LDTs Argues Elaine Lyon of ARUP


Elaine Lyon, President, AMP; Director of Genetics Division, ARUP

Bio and Contact Info

Listen (5:53) How do you determine clinical validity?

Listen (5:41) Whole genome or exome?

Listen (5:41) LDPs not LDTs

Listen (5:40) Having both CLIA and FDA regulation too onerous

Listen (3:25) Not convinced that FDA cleared means a better test

Listen (2:32) Opting out of incidental findings

Elaine Lyon has become a key figure in genomic medicine. As the Medical Director of Molecular Genetics at ARUP Laboratories, she's at the bench developing clinically relevant genetic tests. Serving a term as President of AMP, or the Association for Molecular Pathology, she is a popular speaker on the diagnostics conference circuit and is certainly able to talk from an overall industry perspective. She joins us as part of our series Regulation and Genomic Medicine.

Beginning with questions about her work in the lab, the interview quickly moves on to Elaine's thoughts on regulation. Recently, Elaine co-authored a paper arguing that we should not be calling the tests laboratory developed tests, or LDTs, but rather laboratory developed processes, or LDPs. Her point is that the test is not the product, but rather the report that's delivered to the physician. She says we should be focusing on the process of genetic testing because a lot depends on the professionalism of the lab tech doing the test. As a process, Elaine continues her argument, the products are not actually in the domain of the FDA.

As guests have noted on this show before, the diagnostics industry has suffered from low quality testing. There are the three issues of analytic validity, clinical validity and clinical utility. It's been argued that regulation by the FDA can improve the quality of the testing. Elaine is doubtful of this argument.

"I am not convinced that simply having an FDA cleared test means it's a better test," she says.

She feels that more regulation is just too onerous. Rather than having two separate governmental regulatory bodies--CLIA and the FDA--examining and approving the testing, Elaine says that we should enhance CLIA.

Elaine warns that at a time when labs are not getting reimbursed like they used to, adding FDA regulation will increase the cost of genetic testing. This may mean that labs won't be able to offer these tests at a time when the technology is dramatically better.

We end with a discussion about the recommendations coming out of the recent ACMG meeting.

Podcast brought to you by: Myraqa Clinical Research: The CRO for Point of Care and PMA Diagnostics.

Sample Prep for Clinical Sequencing with Sami Amr, Partners Center


Sami Amr, PhD, Director of the Sequencing Core, Partners HealthCare Center for Personalized Genetic Medicine (PCPGM)

Bio and Contact Info

Listen (8:30) How is NGS sample prep improving in clinical applications?

Listen (3:22) Will we get to a one-touch system?

Listen (5:12) Panel or exome?

Listen (4:12) Lab tech proficiency

To finish up our NGS 2014 series, we're joined by Sami Amr, Director of the Sequencing Core at Harvard's Partners Center. Sami and his colleagues are using NGS for ever more clinical applications. How must sample prep improve as genomics goes clinical? Will we ever get to a one-touch system? Which sequencing platform does Sami prefer? These are some of the questions the hands-on lab director addresses in today's interview.

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.

Stefan Roever Talks the Future of Next Gen Sequencing


Stefan Roever, CEO, Genia

Bio and Contact Info

Listen (7:34) Update on Genia technology

Listen (3:31) How will you compete with Illumina?

Listen (7:52) How will genomics scale in the clinic?

Listen (3:52) Encouraged to see nanopore sequencing now go commercial

Listen (3:26) Archaic regulatory environment holding back genomic medicine

Listen (5:10) Are you a believer in the DTC space?

Stefan Rover is the CEO of Genia Technologies, where he and his team are working on the next NGS technology. This space has become dominated by Illumina, who this year announced they had achieved the important benchmark of the "$1,000 genome." Stefan and Genia aim for the "$100 genome." In today's interview, we ask Stefan just what it will take for a new technology to break in to the sequencing market.

Beginning with an update on Genia's nanopore based sequencing, Stefan then goes on to talk about how NGS will scale in the clinic.

"Ultimately you don't want a doctor or the clinic to worry about how much does the instrument cost, how many reagents to order, and at what cost, etc," says Stefan. "All they want to do is provide a test and get an answer. And handling things like analysis in the cloud, or patient confidentiality, or integration with payer reimbursement systems---all of that is something that can be handled in a cloud service that can be integrated with the instrument."

Stefan says that the biggest challenge for genomic medicine is our regulatory system, which he calls "archaic." Speaking directly about the FDA's recent clamp down on 23andMe, he favors a system where there are competing regulatory agencies and where the market itself is allowed to raise the value of genomic tests.

Stefan says he's "absolutely" a believer in the DTC genomics space. Consumers own their genomic data and should be able to access it freely, he contends.

"The consumer should be able to go to any service they want and ask any question they want regarding their data."

The discussion about regulation with Stefan provides a preview into our upcoming series, Regulation and Genomic Medicine, where we'll be interviewing Cliff Reid of Complete Genomics, Anne Wojcicki of 23andMe, Alberto Gutierrez of the FDA, among others.

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.

New to Mendelspod?

We advance life science research, connecting people and ideas.
Register here to receive our newsletter.

or skip signup