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The Clinical Sequencer

Author: 
Theral Timpson

A Feburary 7th article in the online version of Nature magazine began with the line, "Genomics finally came of age as a clinical discipline on November 19, 2013, when the US Food and Drug Administration (FDA) approved Illumina's MiSeqDx next-generation sequencing (NGS) system for clinical use."   

Now, some may argue with this and say genomics was coming of age with the BRCA test from Myriad back in the nineties, or with the use of NGS for cancer treatment, or the rise of prenatal diagnostics.

And some may say that the science just isn't here yet.  There are very few applications.  I was talking recently with a member of the team at Health and Human Services last week who helped draft Obamacare.  She said that most folks in healthcare and most of congress is certainly not aware of KRAS, BRAF, EGFR, etc.  The science is very new and there must be many many more clinical trials.   Furthermore, we've inherited a healthcare system that was designed for infectious diseases and lacks the infrastructure and expertise in molecular medicine. 

But we can all agree that the clearance by the FDA of an NGS platform is a milestone and goes another step to fulfilling the promise of genomic medicine that began many years ago.    

Last week, I moderated a panel discussion, “The Clinical Sequencer,” at Select Bio’s conference in San Diego, NGS: Research to Clinic.  Daniel Grosu, VP of Clinical Development and Medical Affairs at Illumina, played a large role in getting the MiSeqDx platform FDA approved.  He joined us on the panel among with a terrific lineup of four other experts in the space.  I think highlights of their comments deserve to be written down.

Daniel Grosu, VP Clinical Development and Medical Affairs, Illumina

Daniel was brought on at Illumina in 2011 as their first Chief Medical Officer (a position which is now filled by the former head of the NCI, Rick Clausner).  Daniel said that the process of getting approval for MiSeqDx took about eleven months total.  Because the FDA had not approved anything like this before, they had to figure it out as they went along.  For example,  PCR and Sanger sequencing were used to verify the quality of the Illumina NGS platform, even though neither of these technologies have FDA approval in this particular context.

Daniel was keen to explain that there were really two approvals at the FDA.  One was for the MiSeqDx Cystic Fibrosis Assay and the other was for the open platform with reagents.  

He also confirmed that Illumina is actively seeking big pharma partnerships for CoDx development with the now approved platform.  Earlier this year Illumina announced that they would be collaborating with the biotech giant, Amgen, to develop an NGS-based companion diagnostic for their colorectal cancer  drug, Vectibix.  

Hakan Sakul, Executive Director and Head of Diagnostics at Pfizer

Another one of those partners might be Pfizer, who’s Head of Diagnostics, Hakan Sakul joined us on the panel.  Of course Hakan wouldn’t verify wether Pfizer is partnering yet with Illumina on the newly approved platform, but he said that he’s very excited about the opportunities with NGS.  Hakan said that NGS provides some clear advantages over PCR and earlier in the day he even mused about whether NGS would replace PCR.  

Hakan pointed out that clinical sequencing offers clinicians the opportunity to do research and medicine at the same time.  With a PCR test you have to know what you’re looking for, but NGS provides a more robust tool for discovery.  This will be a challenge for regulators, Hakan said.  So far to get a diagnostic test approved by the FDA, a company like Pfizer has to choose a target, or panel of targets, which are spelled out as part of the test.  He left the question open as to how a regulator goes about approving a test where the specific target is yet to be discovered.

Shawn Baker, CSO, AllSeq

Shawn Baker keeps track of all of NGS platforms--new, old, and upcoming--for the neutral sequencing marketplace, AllSeq.  As a panelist he said he had more questions for the others than answers.  He asked Daniel Grosu about the tension that is sure to arise at Illumina now that they have a MiSeq for research and one for the clinic.  These are two very different markets.  The research market accepts and expects constant innovation and upgrades, where the clinical market must have a platform which is stable.  

Daniel confirmed that these markets were different, but said that there is opportunity to improve the clinical platform with regular upgrades.  He said that Illumina wouldn’t slow down in providing the research market with continual innovation.

I asked Daniel if Illumina planned to make a platform expressly for the clinic.  “The MiSeq,” he replied.

Nazneen Aziz, Director of Molecular Medicine, College of American Pathologists

Our fourth panelist, Nazneen Aziz of the College of American Pathologists, or CAP, has been pioneering the standards for NGS that will be necessary in pathology labs.  She said that her team at CAP is not so much focused on the instrument--it doesn’t matter what platform a lab uses--or the bioinformatics software, as much as whether the lab tech can call the disease variant correctly.  As part of the testing, Nazneen and her team have the lab sequence a known genomic segment and call the variants.  This is then compared to CAP's own gold standard for which they used various NGS platforms, including Illumina and Complete Genomics.

CAP testing also includes a profiency test for the lab techs.  Nazneen says that most pathology lab techs are sufficiently qualified to use an NGS platform.

Nathan Pearson, Genome Scientist, Ingenuity/Qiagen

It appears that Illumina will soon have some competition with their MiSeqDx platform. Qiagen has announced their own clinical NGS platform, the GeneReader, to be commercialized later in 2014.  (Stay tuned for our interview with Dietrich Hauffe, VP of Life Science at Qiagen to be published next week.)  

Our fifth panelist, Nathan Pearson, has been working in bioinformatics at Ingenuity Systems.  The company was bought last year by Qiagen.  Nathan said he couldn’t say much about the GeneReader yet, but confirmed that yes, it would come out in 2014.  Qiagen has worked with the FDA for many years and boasts an impressive lineup of approved diagnostic kits.  With an NGS instrument along with their sample prep kits, their PCR kits, and their newly acquired bioinformatics assets (they also bought CLC Bio last year), Qiagen is set to have an impressive end-to-end workflow to offer clinical labs.  Controlling the entire workflow will give Qiagen the opportunity to raise the standards for clinical sequencing.   Now the process is very modular with lab techs using various suppliers for different steps.

I asked Nathan how will we know when a bioinformatics platform is robust enough.  He replied that "it’s like the early days of the computer.  Were they ever good enough?  No.  But did they help out a lot?  Yes."  Nathan said that we are still a long ways away from knowing what to do with “the genome.”  He said that when a healthy person gets their genome sequenced it might not do much for them now, but it can do a lot for biomedical research.  He encouraged everyone in the room to get their genome sequenced and donate it to research.

Clinical sequencing is a very exciting and fast changing space.  In a year or two from now there could very well be other players who we don’t mention today, someone with a disruptive technology.  

No matter what whiz bang clinical sequencing technology that comes along, there is a big challenge that remains for the business model of diagnostic companies.  Diagnostics are just not valued highly like therapeutics.  

I've heard from industry leaders that someday we'll be saying CoRx, that the value will be in the Dx side and the Rx will supplement that.  But we're a long ways from that today.  In fact, the price for Dx  continues to drop.  Myriad, since the Supreme Court decision on gene patents, has faced a drop by half of their reimbursable price.  Why is it we don't want to pay for the tests that diagnose a disease?  They cost a lot of money to develop. (It’s not as costly as developing a therapeutic, but it is very high--in the hundreds of millions.)   Is it a cultural issue?  We don't value naming a problem like we do the solution?   I left the panel with this open question:  What is the biggest barrier to raising the value of diagnostics?  

 

Was the FDA Right to Shut Down 23andMe’s Marketing?

Author: 
Eric Schuur

The FDA was right to act in November by asking 23andMe to stop marketing its personal genome service. Now, don’t get me wrong, I have been rooting for 23andMe to succeed at what they are doing in the Consumer Genomics (CG) space. I have been hoping that “opening the door to the genome” would produce some interesting new insights about biology that might escape traditional scientific inquiry. I have been hoping, too, that taking genetic information directly to the people might further empower individuals in the health care system and begin to counter balance the medical profession and insurance companies. However, once the FDA communicated to 23andMe that their offerings looked like a medical device to the FDA and would the company please take certain steps, 23andMe’s choice was really to comply or break the law. Based on what’s public, the action by the FDA in November should have been no surprise to the company.

So, the real issue many are unhappy about is whether CG should be regulated at all. Should the FDA have categorized 23andMe’s personal genome service as a medical device in the first place? There is room for debate on that point. However, at that time it was a reasonable position for the FDA to take (remember, in 2010 the CG industry was not without controversy over quality and utility, at least according to the GAO). Furthermore, the industry, including 23andMe, was distributing what had for many years been considered medical advice. I, for one, am generally pretty happy to have an agency try to make sure that the medical products that I use are of reasonable quality. That is not the case in other parts of the world.

Since that time things have changed. Some studies have shown that CG info is probably mostly harmless. It may well be time to engage more deeply in the conversation over what, if any, regulations should bear on genetic information. While many are of the opinion that there is no harm to one knowing one's own genetic code, I'm not so sure. I can certainly envision a large population of people deciding to take their health in their own hands, making a bad choice based on erroneous genetic information. Maybe we should let them do that. Maybe that is really what we are debating in the guise of the 23andMe/FDA issue.

Genome Management, Genome Factories and Other Audacious Goals Discussed at PMWC 2014

Author: 
Ruby Gadelrab

On January 27-28,  thought leaders from across multiple industries assembled at the Computer History Museum in Silicon Valley to discuss key themes in personalized medicine at the Personalized Medicine World Conference 2014 (PMWC).  Having been in the genomics space for over 17 years and now part of the team that leads Invitae’s marketing and commercial development efforts, I have been attending PMWC since its inception in 2010.   Over the past 4 years, it has been fascinating to see how rapidly the field is advancing.  Importantly, despite the numerous challenges we face in democratizing genomics, there are inspiring opportunities ahead. This year’s meeting was filled with incredible speakers and ideas, and as much as I wish I could capture them all – I can only scratch the surface by highlighting the few themes I believe will be most impactful on our industry in the coming years.

From $1000 Genome to Genome Factories

The meeting opened with Jay Flatley, CEO of Illumina and recipient of the PMWC luminary award. He revisited milestones in personalized medicine over the last 10 years and showcased how Illumina’s history is intimately intertwined with this story, from genomics research, to translational medicine, to personalized medicine in the fields of cancer, reproductive health, and NIPT.

Most notable was his statement that “demand for genome factories is about to explode,” referencing Illumina’s recent announcement of a new platform HiSeq X, which boasts the ability to sequence a $1000 genome. In order to get to this price point, you need to purchase 10 of these new instruments (approximately $10 million). Economies of scale get you to the $1000 genome and means that a lab with this set-up, can sequence 18,000 genomes a year.  This is a key landmark in advancing and democratizing personalized medicine and making it more widely available to the masses.

In addition, Flatley emphasized that to really use genomes in medicine, “Big Data” sets need to be generated and shared between researchers and clinicians.  He then announced Illumina’s goal “to get 1 million sequenced oncology patients into a database within the next 5 years.” Not an unachievable goal for the man whose company brought us the $1000 genome.

Entering A New Era of Genome Management

Flatley subsequently participated in an impressive panel titled, “10 Years into Personalized Medicine: What Have We Learned and What’s Next.” Other panelists included InVitae founder and CEO Randy Scott, Kim Popovits of Genomic Health, Brooke Byers  of Kleiner Perkins Caufield & Byers, and Ralph Snyderman of Duke University.

Snyderman opened the panel with "the ability to predict, track, and precisely define the nature of a disease was one of the revolutions of medicine. Although personalized medicine started over 10 years ago and is potentially a $450 billion industry, things haven’t actually changed in healthcare that much. It’s still not personal, prospective, proactive or planned.”

Popovits shared that upon joining Genomic Health 10 years ago, Randy taught her about The Innovator’s Dilemma and the concept of “disruption.” As a pioneer of genomic diagnostics, she reflected upon some of the challenges they faced with Oncotype Dx. “If we had tried to approach this as a traditional diagnostic, we would have failed…I hadn’t anticipated that payers and regulators weren’t ready for genomic medicine.” 

Scott also reminisced of his early days at Genomic Health, “we were wonderfully naïve… no one in the pharma industry was prepared to incorporate genomic data into routine clinical trials….  We just had to bypass pharma and go straight to the physicians.”   “Genomic medicine is here to stay,” added Popovits.  “The value is just too high. We will overcome the barriers and there will be a shift to prevention and early diagnosis.” In looking ahead, Kim predicted, “the next decade will be a revolution as transformative as antibiotics.  Every cancer patient will be sequenced.”

Scott’s vision of the future was influenced by his own family experiences of inherited genetic disease – he tells the story of his nephew's daughter who had galactosemia, a rare Mendelian metabolic disorder.   “5-10% of the population suffers from a Mendelian disease…. Our goal at Invitae is to aggregate all the worlds’ genetic tests into a single assay for less than $1000,” commented Randy.  “We are focusing on germline genetics and the future is family health and comprehensive genome management.“ 

Genome management 

What is genome management? At its simplest, over the coming years, as the price of sequencing drops further and further, more and more people will have their genome sequenced for a variety of reasons: medical applications, carrier screening, pharmacogenomics, eventually newborn testing at birth, or just because people are genetically curious about themselves and their families.  As InVitae CMO Jill Hagenkord points out, “DNA information will just exist.”

At Invitae, we require a physician to order and interpret our medical tests. However, we believe that every individual has the right to access their own genetic information and that each individual should own their genetic information.   When it becomes common that a plethora of genomic information just exists, the questions will become: Where will you store your genomic information safely and securely? How will you be able to access it?  Who will you choose to share it with and how?  How can you benefit from it?

That’s one of our goals at Invitae: to make genetic testing accessible to a billion people on the planet and then to safely and securely manage it for them.  Enter an era of genome management.

Personal “Omics Cloud” and the Rise of the Wellness Industry

Dr. Leroy Hood, the scientist who discovered how to automate DNA sequencing that revolutionized biomedicine and forensic science, added another dimension to the concept of genome management.  He proposed that, in the future of this space, every individual would have his or her own personal  “Omics Cloud.”

Hood started off talking about the need to unite the stakeholders in personalized medicine through education.  He also echoed Flatley’s sentiment regarding building “big data” databases that can be shared by various stakeholders. 

He proposed that a step in getting there is conducting a “longitudinal Framingham type study of 100,000 patients.” His plan is to collect data three times a year from every patient, including “genomic and proteomic data, clinical chemistry, microbiome, and biomarkers from the heart, liver, brain, and blood.” Further, he also suggests layering in “quantified self “ phenotypic data.  This “Big Data” set can then be mined for actionable variants to reveal the early origins of disease.

This mammoth project will create a data cloud for each individual that can track his or her transition from wellness to disease. Eventually, we will be able to optimize factors for wellness. Hood predicts that this initiative will reduce costs, improve outcomes, and result in the creation of a “wellness industry that dwarfs the healthcare industry.”

A Match.com for Clinical Trials

Many companies claim that they put patients at the center of their approach, but by virtue of the questions from the audience and the panel discussion, clearly we as an industry are not succeeding at this goal. 

Brave Neil Schiffman, stage IV lung cancer fighter, was an inspirational part of a panel entitled, “Personalized Medicine in Oncology Today”.  He is a classic example of a growing movement of patients who take matters into their own hands to self-educate and self-advocate. “I have my patient advocacy gene turned on,” he said. 

He shared his experience of searching for and extensively researching clinical trials, which he eventually participated in for a year before going back to his Tarceva treatment. Clinical trials give cancer patients hope, Neil continued, "the old model was that entering a clinical trial was the end. Today, it's actually the beginning of treatment.” 

With less than 10% of patients participating in clinical trials, it’s obvious that we have a problem and need to rethink our strategies around clinical trial recruitment.  One of the most poignant moments of the meeting was the emotional plea to the panel from a woman in the audience who moved us all to tears. She had sadly lost her husband to glioblastoma just last week, and she shared their story of how once her husband was diagnosed, it was very hard for them to find any clinical trials.  They didn’t know who to talk to or what resources were available to them.

“It’s terrible that there are still questions of what do I do next?  How do I find a clinical trial?” lamented Edgar Staren (CTCA Medicine and Science) to which George Demitri (Dana Faber/Harvard) responded,  “we need a match.com so that patients with metastatic cancer can find clinical trials.”

Marty Tenenbaum of Cancer commons supported this further. “We can cut a decade out of the clinical trial process if we can connect patients and  researchers who need each other,” he said. “Your zipcode is not the area to find the right clinical trial for you, it is your molecular zipcode.”

The inclusion of a patient on this panel made it one of the most impactful sessions of the whole conference.  We should emulate this approach. Edgar Staren suggested that “all industry leaders should include patients in their board meetings…it’s always helpful.” Neil supported this, saying, “ask the patients to participate in the processes, in real time and you will get a better outcome.... don’t wait for patients to come to you. They're often very sick.” 

The participation and opinions of patients and patient advocates in the audience and panels, provokes a sense of urgency that we as an industry need to act swiftly to help make their voices heard and include them in our processes. We REALLY need put the patients at the heart of everything we do. “Every patient is a clinical trial of one,” said Tenenbaum. Disease is personal to every individual, but medicine is not personalized enough… at least not yet.

Free the Data, Unite the Data, and Share the Data

A theme that ran throughout the meeting was the need for patients,  clinicians and researchers to share data in order to accelerate our understanding of disease and develop better diagnostic, detection, prevention, and therapeutic strategies.  

Flatley emphasized that Illumina builds and supports strategies for genomic data sharing.  Randy Scott echoed this sentiment when he mentioned the “Free the Data” movement, a grass roots effort to create a database of BRCA variants that can be shared by the scientific and medical communities. “Genes should be free and not patented,” according to Scott.

Marty Tenenbaum, himself a cancer survivor, summed it up nicely. “Cancer is a great equalizer. Most of us will confront it at close range at some point in our lives, and when you do, you will want access to collective knowledge.”

Ruby Gadelrab (@divabiotech) is part of the team that leads the marketing and commercial development initiatives at Invitae.  This blog was originally posted at www.invitae.com/blog.

 

Mendelspod and Chempetitive Walk into a Tequila Joint . . .

Author: 
Theral Timpson

It’s no joke.  And it wasn’t for the Superbowl.  

Last Thursday Mendelspod and Chempetitive Group hosted a special networking and panel discussion event in a classic tequila lounge in San Francisco.  We were joined in this lounge by five stellar bioinformaticians and an audience of about fifty.  I’m not going to give all the juicy bits of the discussion here because we want to incentivize the audience to join us and not stay home or at the office and read about it.  In our uber connected online world, there is something to be gained also from meeting in person, socializing, and participating in a live discussion.

Panelists and Moderator:  Bob Rogers of Apixio, Theral Timpson of Mendelspod, Andrew Carroll of DNAnexus, Jonathan Hirsch of Syapse, Matt Landry of Dx Engine, Mirko Buholzer of Complete Genomics

The Thursday event was a nice success for us, Chempetitive, and the topic of bioinformatics.  We were able to assemble an outstanding lineup of panelists on the topic, “How Will Bioinformatics Scale?”  Represented on the panel were some of the leading companies in genomic medicine:  Complete Genomics, DNAnexus, and Syapse.  Also on hand was a lead scientist from Apixio who is offering unique informatics in the healthcare space.  It was great to hear data scientists who have been primarily focused on omics data engage with someone from the healthcare side.  And visa versa.  When you look at overall healthcare big data, genomics is just a small portion.  Below are some memorable lines from the panelists (thanks to @EClausen and @DNAnexus for tweeting):

“The big issue is accuracy.  And if you want truly accurate health records, big data analytics is the only way.”  Bob Rogers, Apixio

“Genomics is cool.  But right now there are infrastructure issues when it comes to delivery.  It’s like driving a fancy new truck over an old rickety bridge.”  Jonathan Hirsch, Syapse

“Data centralization is the key to solving a lot of accuracy issues.”  Andrew Carroll, DNAnexus

“We need a consumer push, not just clinical, for bioinformatics to really have an impact.”  Mirko Buholzer, Complete Genomics

“There are bigger issues in healthcare than bringing genomic data into the clinic.”  Matt Landry, DxEngine

(More quotes on Twitter, under #bioinformatics on Jan 30th.)

This is the first event that Mendelspod has put on, and the first for Chempetitive in the Bay Area.  And we’d like to continue.  Perhaps when you peruse these pictures you’ll be inspired to join us in the future.  Today, we’re asking for your suggestions on topics for future events.  Click here and send us a note.

Please comment also on when and where you’d like to join an event.  Is afternoon better than evening?  Is Palo Alto better than San Francisco?  We want your ideas.

Mingling at Tres Lounge
 
Karl Glaub, Curiosity Works
 
Matt Landry, DxEngine; Helen Cao, Qiagen
 
Nnamdi Ihuegbu, Life Tech  ; Angela Anderson, DNAnexus
 
Panelists

2013 Sequencing and Bioinformatics in the Rear View

Author: 
D Matthew Landry

With the "How Will Bioinformatics Scale?" panel discussion coming up, now is a good time to reflect on the last year of DNA sequencing and bioinformatics industry gyrations. Besides, we're already 1/12 through the year, so one had better reflect quickly before last year and this year blend together.

(Can I pretend that such time-blurring is in fact an advanced subconscious shortcut to update the mental models without burdening the model skeleton with disjointed, soon to be deprecated facts, rather than a possible case-history indicator of APOE status?)

Anyway, my observations over the last year are necessarily colored by a distinct commercial perspective. Caveat reader.

Sequencers for the clinic

I should perhaps start and finish with Illumina ($ILMN), but I won't. (Or did I just?) Rather, QIAGEN ($QGEN) is the intriguing actor this year. Despite little visible progress on bringing the GeneReader to market (though there were some nice mechanical shells at the AMP meeting in Phoenix), they demonstrated their sincerity by acquiring the leading pathway analysis and desktop sequence analysis bioinformatics companies: INGENUITY and CLC bio. INGENUITY, especially, speaks to $QGEN's laser focus on powering routine clinical molecular diagnostics. They didn't take long to follow up with an early-access program for the clinical version of their Variant Analysis web tool, with a killer roster of clinical/scientific advisors. My impression: if anyone is going to be a serious contender for arming the world's molecular pathology laboratories with NGS-based diagnostics capability, it's $QGEN. Even without the GeneReader.

Bioinformatics in the Cloud

While $ILMN made an interesting counter-acquisition in NextBio, I found the steady progress of BaseSpace's capabilities more important. While DNAnexus was getting v2.0 of their platform off the ground, StationX was prepping and launching GenePool, and other ab initio or grant-derived players (Seven Bridges Genomics, Maverix Biosciences, Arvados, GeneStack) were escalating the cloud-based informatics war, BaseSpace was relatively quietly evolving, sheltered safely under their 1-button ("check here to upload to BaseSpace") ease-of-use for data capture. It's usability hooks like that we need to watch.

The industry has very quickly fronted a diverse cast of contenders offering similar levels of functionality on virtually identical infrastructures, raising the bar quite high. Not bad, considering only two years ago, "the cloud" was not supposed to be fit for genomics.

Not to gloss over the piles of interesting papers published over the course of the year, but, some of the more interesting journalism came from big research: ENCODE, and Dan Graur's colorful deconstruction of it. Or, how about TCGA, and the realization that no one can easily use the data (see NCI's $20M call for interest on building ... wait for it ... a cloud based informatics platform).

Other sequencing tech goes quiet

Because the sequencing instruments are already so good, I think we all sort of stopped agonizing over it. After resetting shareholder expectations, Pacific Biosciences ($PACB) continued to iterate and tailor their areas of expertise. Oxford Nanopore continued not to offer data (though brilliant marketing, again, at ASHG, by announcing a signup sheet for a beta program; one step shy of just putting the whole MinION on IndieGogo). What about Life Technologies ($LIFE)? Caught up in acquisition news and with its loss of marketing momentum on the Ion Torrent side, its position as second-place lead in the sequencing market is starting to feel more like the first loser position.

Software investment ramps up

As venture investors start doubling down on their bioinformatics portfolios (rounds for Spiral Genetics and Bina Technologies and SVBio and Knome and Syapse and Personalis and Curoverse and more), everyone is shifting their rhetoric to focus on clinical informatics.

A question in my mind is whether clinical bioinformatics will turn out highly fragmented and chaotic like research bioinformatics, or whether it will coalesce around a couple of preferred vendors. (Full disclosure: my current startup, DxEngine, is developing software solutions to help pathology labs produce actionable clinical reports.) Perhaps the only winners will be Amazon Web Services ($AMZN) or Google Compute Engine ($GOOG), selling the computing infrastructure pickaxes to the bio data miners.

FDA guidance

The FDA has obligingly offered brilliant political doublespeak with respect to LDTs, connected devices, EHRs, and the like: they seek to reduce regulatory uncertainty by claiming carte blanche jurisdiction, issuing guidelines, and then draping it all with "enforcement discretion." Thumbs-up for guidelines, but pardon me for not feeling certainty when enforcement policies are riddled with discretion. Nonetheless, double thumbs-up for an FDA-cleared MiSeqDx.

2014 off to the races

Which brings us into the beginning of 2014, where we can already see a continuation of double-down investments, $ILMN making serious instrument waves, and re-excitement for delivery by Oxford Nanopore and $QGEN. And, clinically, we're all watching to see how reimbursement in general and CMS in particular responds to the growing body of diagnostic tests and the subset with clinical utility.

2013 was a fun year, and if January is an indictor of 2014, I might need to do a mid-year update just to keep it all straight in my head.

Why Scientists Should Study Philosophy

Author: 
Theral Timpson

Since the first human genome was sequenced, there has been disappointment in and with the life science community over the fact that we haven’t figured out more of the big biology problems.  Cancer, for instance.  Oh, there’s been rapid technological progress.  Illumina announced this year that the human genome that cost $3 billion to sequence originally can now be done for the cost of a root canal, or $1,000.  

So why the disappointment?  Why were scientific expectations so high?  

At the turn of the 20th century, the British chemist and physicist, Ernest Rutherford said, “all science is either physics or stamp collecting.”   It’s a cute statement.  But how true is it?  Should scientists study biology in the same manner that they study chemistry or physics?    What is science, what really is the genome, and should we rethink our basic study of biology?  

To pursue these questions, we’re launching a new series this week, “Why Scientists Should Study Philosophy.”   We’ll be interviewing philosophers of science.

Huh?  Philosophy of science?  What has philosophy to do with science?  A couple years ago, the scientist Stephen Hawking went so far as to say that “philosophy is dead.”  He argued that philosophers had not kept up with physics well enough to even be relevant any more.  (I’ve enjoyed throwing this question to several of our guests here at Mendelspod.  None of them have  wanted to agree with Hawking.)  The boundaries between science and philosophy are not that clear.  In fact, what we call “science” today used to be called “philosophy.”  Francis Bacon, who came up with the “scientific method” and is considered the father of modern science, was most notably a philosopher.  

Last year, Steven Pinker, the well know neuroscientist, wrote a piece entitled, “Science Is Not Your Enemy,"  where he argued that those in the humanities need not be afraid of science.  For Pinker, science and the humanities can work well together; in fact, science can offer new ways of looking at the arts.    On the other hand, one might imagine the article, "Philosophy Is Not Your Enemy," aimed at the world of scientists.  In the spirit of Pinker's piece, this article might argue that philosophy could be used more to aid in science.   In fact, this is exactly what philosophers of science offer.  

In this new series, we'll be asking what is science, what is philosophy of science, and what can philosophy bring specifically to the study of biology.   I’ll preview some of the themes here:

Anti-Reductionism

Some philosophers question the notion that there is one science.   They’re known as anti-reductionists.   Reductionists argue in the vein of Rutherford that all things can be studied scientifically and this study will ultimately end up with the study of physics.  They would argue that this blog I’m writing today can be looked at in terms of sociology and my own psychology which in turn can be studied in terms of neuroscience, which can be studied in terms of biology, on to chemistry, and finally to physics.  Anti-reductionists refute Rutherford’s notion that all science is either physics or stamp collecting. These anti-reductionists such as our first guest in the series, the philosopher of biology, John Dupre,  assert that the study of biology presents its own problems and should be done differently than the study of physics or chemistry.  

Animals Are Their Own Animals

If all the subatomic particles that exist in an elephant are placed somewhere else in the universe, is the the "group" of particles still an elephant?  John Dupre argues, no.  Biology is more complex than that and depends to a great deal on context.  Dupre questions the popular idea, for example, that we can simply transfer the abstract principles of engineering to sythetic biology and reduce living things to “biobricks.”

Looking at biology from a philosophical perspective could yield great dividends.  How much of what we now realize was an overly gene-centric view of biology came from the scientific traditions developed within the study of physics where the race was always to find the smaller particle to explain larger structures?  Have biologists been too narrow in their focus?

The disappointment that has bloomed since the sequencing of the human genome perhaps shows a great naivety on the part of biologists that this single, albeit tremendous, undertaking would yield immediate understanding and direct connections to all disease.  Again, have biologists been thinking too much like physicists?

Language and Science

All science is actually done through the aid of language.  We think in language.  We use language to communicate and collaborate.  Of course, the scientific method itself is language.  Is it not fair to ask what limitations language imposes on science?  Does there have to be a shift in language, however small, before a new scientific discovery or breakthrough happens?

These are some of the questions we’ll pursue in this series.  We aim to stimulate more philosophical thinking and more questioning into the nature of science and the assumptions upon which our industry is built.

One Week to Special Bioinformatics Event

Author: 
Theral Timpson

On January 30th, some of the best bioinformaticians in the industry will gather in the back of a tequila lounge in San Francisco's swanky industrial SOMA district for networking and a panel discussion:

  

"How Will Bioinformatics Scale?"

Representatives from Complete Genomics, DNAnexus, Oracle and other companies will take us into their world and share their visions for the future of bioinformatics.  The main focus of the evening will be the "infrastructure" side of bioinformatics, which can bring up some interesting questions: 

  • In a world where IT companies have already scaled large (Google, Twitter, Amazon), what is unique about the bio industry that must fall into place before a similar scale can be reached?  
  • Will one site emerge that does it all, that is able to combine the "big data" and compute along with all the "metadata" gleaned from omics and other research and patient medical records? 
  • If the cost and installation of hardware is a non issue in today's world of Amazon Web Services (Cloud Computing), then what indeed are the obstacles for the new infrastructure?  Is it the accuracy of the data?  And if Twitter uses "a window of time" and Google uses "numbered pages" to prioritize a search, what prioritization should be used when looking at the genome?

These are some of the questions we'll explore in an event hosted by Mendelspod and Chempetitive Group.  Join us for a fantastic panel, high level networking, and some great Mexican food and an open bar at Tres Lounge in SF, January 30th.

Click here for details.

The Mendelspod Guide for Listening to Podcasts

Author: 
Theral Timpson

Podcasts are one of the most popular forms of media today.   Usually offered as an mp3 audio file, the podcast is like a slice of radio but with much more flexibility.  A podcast can be listened to at any time and pretty much anywhere in a number of ways. 

Our audience at Mendelspod is technically savvy.  Still, from time to time we get a question about how to listen to the show.  Most often it’s “how do I download the Mendelspod show to my iPhone?"  So today we’re putting out this guide that goes over the 5 ways of listening to a podcast.

1.  Play podcast and listen with your desktop or laptop.  This is by far the most straight forward way to listen to Mendelspod, yet perhaps the most limiting in that you have to be at your computer to listen.

2.  Download the mp3 file and listen through your media player.  Perhaps you only have time to listen to part of a podcast and not all.  Yet if you close your browser window, you lose your place.  There is a way to download the podcast to your computer and play it at your leisure.  

How To Download a Mendelspod Podcast To Your Computer

The process of downloading the audio file to your computer depends upon your browser and whether you are on Windows or Macintosh. 

Windows

For Internet Explorer, right-click on the MP3 Audio file (located on the bottom grey bar of the podcast player) and choose “save this link” from the pop-up contextual menu.

For Firefox, alt-click on the MP3 Audio file and choose “save this link” from the pop-up contextual menu.

Macintosh

For Safari, control-click on the MP3 audio file and choose “download linked file” from the pop-up contextual menu.

For Firefox, control-click on the MP3 audio file and choose “save link as” from the pop-up contextual menu.

3.  Subscribe to podcast through RSS.  Let’s say you’ve listened to a podcast on Mendelspod, and now you want to subscribe so that each time we produce a show, you are notified.  One of the most common ways to subscribe is through RSS feeds.  

How to Subscribe to Mendelspod through RSS Feed

On the Mendelspod Home page, click RSS Feed.  This will take you to a page powered by FeedBurner listing all of the recent Mendelspod content.  From here you can either play the mp3 or download it just as you do from the Mendelspod site.

Also on this page, you’ll see the chance to subscribe via web-based “podcatchers” such as Podnova.com or with iTunes.  

You can also have the Mendelspod feed delivered to your mailbox each day buy clicking the link  on Mendelpsod Home RSS via Email.

4.  Subscribe to Mendelspod through iTunes.  iTunes is by far the most common software used to subscribe to a podcast and the iTunes store is the largest collection of podcasts.  

Simply open iTunes (you may need to download first) and click File, then Subscribe to Podcast.  iTunes will automatically populate the most recent shows from Mendelspod.

5.  Listen to Mendelspod on your phone or tablet.  Now we’ll get into the fun stuff.  Accessing Mendelspod podcasts from your phone means you can catch our show while on the go--at the lab bench, in your car, or at the gym.  

How to listen to Mendelspod on the iPhone, iPad, iPod

I’m listing some links to help out here.  The first is Apple support.  Note that since iOS 6, Apple offers a Podcasts app which makes managing podcasts on your iPhone and iPad quite easy.

http://support.apple.com/kb/HT3281?viewlocale=en_US&locale=en_US

This second link offers a list of alternative podcasts apps in addition to Apple’s own app.  At the top of the list are Downcast and Pocket Casts.

http://appadvice.com/appguides/show/podcast-apps

How to listen to Mendelspod on an Android mobile device

This article published by DigitalTrends.com offers instructions for downloading a podcast to your Android device.

http://www.digitaltrends.com/mobile/how-to-download-listen-to-podcasts-android-ios-iphone/

How to listen to Mendelspod on a Windows 8 phone

This first article about subscribing to podcasts is offered by Windows phone support.

http://www.windowsphone.com/en-us/how-to/wp7/music/subscribe-to-podcasts

This second article suggest still using iTunes even with the Windows 8 phone.

http://winsupersite.com/windows-phone/windows-phone-8-tip-enjoy-podcasts-go

Finally, this third article gives a detailed comparison of 3rd party apps for Windows Phone 8.

http://allaboutwindowsphone.com/features/item/18410_Podcatchers_podcast_managers-c.php

There you have it.  5 different ways to listen to the Mendelspod show.  Many of our shows are video and all of these can be accessed over Youtube and the Youtube app as well.  But for the regular podcast fans in the audience, we always offer the audio version of every show.

Happy listening!

Note:  Please write in and tell us how, when, and where you listen to Mendelspod.  Over the next few weeks, we’ll be publishing these stories to share your podcast listening ideas with others.

Democratization of Bioinformatics?

Author: 
Moray J Campbell

In cancer research, and other arenas of biomedical research, there are many challenges to ushering in an era of personalized medicine. Technical, logistical and ethical challenges need to be met to allow genomic-based diagnosis and prognosis in cancer. However, one of the greatest challenges is to generate a widespread democratization of statistical understanding and computational skills in cancer researchers. With the costs of genomic approaches falling, and the increasing desire to apply these technologies, the impact of this skills-shortage is set to become more critical. Beyond specialist centers, one result of this accelerating growth of genomic approaches will be to widen the gulf between the capacity of researchers to generate and to interrogate data. Put another way, genomic data interpretation is not able to keep pace with data generation, let alone match the projected rates. In part, this has led to the conundrum of the $1,000 genome with a $100,000 interpretation. There is no easy fix to meeting these challenges.

As a test case of a 40 something wet-lab biologist I know my rock bottom came a few years back when I realized I didn’t even know what I didn’t know. I’m now somewhere towards being something of bioinformatician. By that I mean I’m about half-way through an online MS in bioinformatics at Johns Hopkins University. Already, it’s been a revelation, but at times it’s like crawling over glass; I’m starting to get to the point of knowing what I don’t know! Perhaps the major aspect it has changed in me, is to start to be able to hypothesize on the genomic scale. In my own research I study the cancer epigenome from a translational perspective and aim to combine insight from cell line, tumor models and patient material. I feel I’ve started the long journey towards being able to conceive, design and interpret experiments both in Eppindorfs and at the command line.

In many ways, the challenges in genomics development reflect the emergence of Molecular Biology. From the conceptual start, for example at Rockefeller Foundation, NY, in the 1930’s, molecular biology was a restricted innovation at key national centers. Landmark discoveries followed and of course included the elucidation of the structure of DNA in 1950’s by Watson and Crick. Arguably, however, the democratization of molecular biology only arrived with the commercial production of restriction enzymes and the development of PCR technology by Dr. Kary Mullis in 1983.

Certain parallels can be seen in the field of bioinformatics. One of the earliest references to bioinformatics, for example by Dr. Paulien Hogeweg in 1970. The growth in bioinformatics has been remarkable. In 1988 there were 11 papers in PubMed that used the term “bioinformatics”, whereas in the same year the term “biochemistry” received approximately 14500 references. By 2012, there were 17760 publications with the term bioinformatics and 38946 for biochemistry. Although this is probably a classic Zeno Paradox, at that growth rate bioinformatics will overtake biochemistry in May of this year!

If it took 50 years for molecular biology to become democratized, will bioinformatics achieve the same widespread exploitation, by 2020? My worry, is that the answer is no, because the training of wet-lab biologists is not adapting rapidly enough. The power of molecular biology technology was built on the application of well-understood principals developed within biochemistry. By contrast, bioinformatics has at its center information theory and the exploitation of statistical insight and computational skills. These are both commonly outside of training for wet-lab PhD scientists and MDs, whose focus is generation of gene-centric but not genomic data-sets. Reflecting this training, researchers from these backgrounds are often most comfortable in the qualitative analyses of systems in terms of candidate genes, RNA, metabolites and proteins. However, for genomics applications to be applied requires the democratization of bioinformatics such that many more biologists, at all levels of their careers, have the key quantitative and computational skills required to understand and interpret disease states in terms of the genome, transcriptome, metabolome and proteome. Going forward, for new wet-lab biologists this requires training in statistical sciences and computational skills; for older scientists this may require the sort of retro-fitting that I’m undergoing.

Institutional level change to training at undergraduate and graduate level is paramount. Many institutions have goals of interdisciplinary training with a desire to develop trainees who undertake computational and statistical analyses alongside their wet-lab approaches. As yet no clear consensus has emerged on curriculum design concerning the balance of biology and informatics that needs. To make such changes, graduate programs will need to distinguish between what is worthy and what is necessary in already overcrowded curricula. Perhaps biochemistry falls into the worthy class whereas in the necessary class are a greater emphasis on biostatistics combined with programming skills. Another way to think about this challenge is to predict for newly graduated wet-lab PhDs what ratio of time will they spend between the computer and the pipette. For me, I believe that the ratio will be 80% computational approaches and 20% in the lab testing the predictions from these analyses. Of course, I say this to be provocative; maybe these ratios are too extreme, and maybe not every program needs to change? However, if graduate programs are designed to generate interdisciplinary scientists, then my thoughts are that these are the types of discussions that need to occur. For many programs, this will require making computational approaches an everyday part of research. I joke with our PhD students that we’ll take Excel and graphpad off the computers and only allow them to use R for data handling and analyses!

With more researchers able to undertake some level of bioinformatics analyses and appreciate its central importance, where will this leave the full-time bioinformaticians? In first instance I’d suggest that this will facilitate a greater, joined up, conversation between the scientists within departments of bioinformatics and next generation of MS and PhD researchers in other departments. An equally important outcome from the democratization of statistical understanding and computational approaches will be the greater appreciation of colleagues who work exclusively in the statistical and computational sciences.

Special Event: How Will Bioinformatics Scale?

Author: 
Theral Timpson

Bioinformatics is one of the hottest topics we cover at Mendelspod.  We see new platforms and software emerge each year to tackle the huge amounts of data coming from NGS, gene expression, Chip-Seq, and other tools.  The issues around bioinformatics can be broken down into "infrastructure" issues on the one hand, and "analytical/interpretation" issues on the other. 

On January 30th, Mendelspod and Chemptetive Group will be producing an evening event with a panel discussion exploring the infrastructure challenges--just how will bioinformatics scale?  This will be a ninety minute discussion with a stellar lineup of key players in bio and health informatics.  We will be starting off with networking and drinks in the back room of Tres Lounge in the SOMA district of San Francisco. As there is limited seating, I urge anyone interested in attending and participating in this discussion to register right away.

How Will Bioinformatics Scale? Hosted by Mendelspod and Chempetitive Group

When: January 30th, 2014

  5 00 pm: Networking and drinks

  6 00 pm: Panel Discussion

  7 30 pm: Networking, drinks, and appetizers

Where: Tres Lounge, 130 Townsend St, San Francisco, CA

Panelists:

These six panelists represent various links along the informatics chain, from data capture to final reporting. My aim as moderator will be to get the various panelists talking to each other, asking questions of each other, and looking for a common challenge they all share.

Cliff Reid is the CEO of Complete Genomics and has several years of experience sequencing human genomes and delivering genomic data to researchers and soon to the clinic. You could say that from his vantage point, Cliff sees the data pretty much end to end. He has worked not only with the best engineers in the tools space, and the most qualified bioinformaticians, he’s also spent time with doctors who are searching for answers for their patients.

At DNAnexus, CTO Andreas Sundquist has pioneered the use of cloud storage for biological data. The company recently released version 2.0 of their Platform-as-a-Service and has secured important strategic partnerships in the space, including Complete Genomics. Late last year the company announced a collaboration with The Human Genome Sequencing Center (HGSC) at Baylor College of Medicine. Part of this partnership involves using Amazon Web Services from which they recently recruited their new CIO.

Fredrick Lee is the Director of Clinical and Translational Informatics at Oracle Health Sciences. Oracle brings some tremendous experience and resources to the life science and clinical informatics space. Already deeply involved in healthcare informatics, Oracle has already begun integrating millions of patient records with hundreds of thousands of whole genome sequences. Prior to joining Oracle, Lee was the CMO of the P4 Medicine Institute.

Jonathan Hirsch is the President and Founder of Syapse, a new company that promises to bring omics into routine medical use. Hirsch boldly claims that Syapse offers the end-to-end solution, a platform for the entire workflow from raw data to reports that doctors will find useful. Winner of the Strata Rx 2013 Startup Showcase, Syapse is already providing their products to several diagnostics labs. According to Hirsch, Syapse is empowering these diagnostics labs to do more in house.

Matthew Landry is the Founder of a brand new company, DxEngine, which will help clinical labs hook their bench-top instruments into an expansive menu of molecular diagnostics tests. Matt says that the labs bring the sampling logistics and tools and that DxEngine will bring the bioinformatics analysis, clinical results reports, and regulatory compliant IT. Prior to starting DxEngine, Matt was the CTO at the bioinformatics company, BioMatters, where he worked to integrate the company’s Geneious analysis software with Illumina’s BaseSpace.

Joining us to represent the healthcare informatics space is Darren Schulte, President of Apixio. This company is working to make medical information more liquid by developing a more connected world, bringing together EHR providers, healthcare providers, patients, and diagnostic device providers. Prior to joining Apixio, Darren led product strategy at the healthcare analytics company, Anvita Health.

Erik Clausen, a Managing Partner for Chempetitive Group, will be on hand to kick off the evening.  Chempetitive Group is a leading marketing and PR firm serving the life science industry and a strong ally of Mendelspod.  We're happy to be partnering with them on this exciting panel event.

Some say we are moving toward a new “utility” for bioinformatics, a new streamlined infrastructure, an internet for healthcare data. Is this true? Just how will bioinformatics scale? Join us as we probe the future of this hot industry on Thursday, January 30th in SF. 

Register here.



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