Biotech Experts Highlight Clinical Sequencing at Rx/Dx Summits

I recently attended the IBC Rx/Dx Summits held in San Francisco in the first week of August 2012.  The meeting was held at the Westin San Francisco Market Street Hotel.  I was attracted to this event because it gave me the opportunity to learn about some of the new emerging market dynamics in next generation sequencing (NGS) and other areas that I track for my firm.

I listened to a talk comparing desktop sequencing systems by Jason Lih, Ph.D., Principal Scientist, SAIC-Frederick.  His talk was called Assay Development for Detecting Somatic Mutations in Cancer by Targeted Amplicon Sequencing: A Technical Comparison between PGM  and MiSeq.

Dr. Lih’s talk compared two desktop NGS machines, the Life Technologies, Ion Torrent, PGM with the Illumina MiSeq. At the beginning of his discussion, he said that he would not say which NGS platform is better.

In his NGS application, he used targeted amplicon sequencing to develop assays to detect somatic mutations in cancer.  Jason said that the PGM used AmpliSeq  v. Illumina’s TruSeq Custom Amplicon  (TSCA) technology.  He said that Life’s PGM requires just 20 ng of DNA sample, whereas the Illumina MiSeq requires 250 ng of DNA sample.  The Life PGM uses a 4-plex #‘316’ chip which outputs 1×200 base pairs of bi-directional sequence in one day plus 4 hours. (or 28 hrs).  The MiSeq takes 27 hrs (or 1 hr. less).

Using a comparison concept that he called the “Cosmic” MOI (Molecule Of Interest), he created a comparison chart comparing 1160 Cosmic MOIs.  He compared both vendor’s reagents.  His results showed that the PGM produced slightly more MOIs.

Vendor Model	Reagents	MOIs	DNA Sample	Run Time	QScore
PGM	AmpliSeq	1148	20ng	28 hrs	30
MiSeq	TSCA	1108	250ng	27 hrs	30

The PGM variant caller was the Ampliseq Reporter.  He used a 3^rd party software from CLC Bio.  The CLC Bio Integrated Genome Viewer showed a Qscore of 30 for each NGS machine.

What is interesting to me is that at end of his talk during the Q&A, an attendee asked Jason for his opinion about which was the best of the two NGS machines that he compared.  He said that his comparison was not intended to find the “best” NGS machine. My take away from his answer was that as far as Jason’s application was concerned, one could use either NGS machine and get comparable/ usable research data.  Also of note is that Roche Applied Systems demonstrated their 454 GS Junior desktop sequencer at the exhibit hall.  I wonder how the 454 GS Junior would compare against the PGM and MiSeq machines.

During the lunch- networking break in the exhibit hall, I met Robert Klein, Ph.D., Chief Business Development Officer, Complete Genomics, Inc. who said that he was giving a talk later in the day.  I attended his talk called: Large-scale, Accurate Whole Genome Sequencing to Enable Genomic Medicine. 

Robert gave a update on the business direction or activities at Complete Genomics (CG).  He said that CG v.1 was about research sequencing and that CG v.2 is more about clinical sequencing.  Dr. Klein said that in 2006 CG developed its proprietary sequencing technology and service model.  By 2011 they had delivered 3,000 genomes to customers.  Robert said that CG now produces 1,000 genomes per month.  He explained that they have a DNA factory in Mountain View and sends the data to its data center in the nearby city of Santa Clara.  CG does this because Santa Clara offers a lower cost for electricity.  CG provides “research ready” data to the customer and the customer analyzes the data.

Robert highlighted CG’s goals as including: Setup a CLIA facility 2H’12, Scale-up quality, Scale down cost, Scale-up throughput and Offering ‘clinical use’ sequencing.  CG will be focusing on new apps. including Idiopathic kids, Refractory cancers, Replacing cytogenetic arrays and Replacing targeted panels.  Dr. Klein also added that CG is interested in Wellness/ concierge medicine and Reproductive genetics.  He mentioned that CG is exploring other market spaces such as Prenatal screening, Newborn screening, and Reproduction Issues.  Dr. Klein predicted that the first areas that whole genome (clinical) sequencing would show clinical utility would be in studies of copy number, neuroblastomas and translocations. Robert said that NGS will likely democratize genomic medicine.

Several speakers echoed TGEN’s David Craig, Ph.D., Deputy Director for Bioinformatics and Professor of Neurogenomics,  comment that “the cost of NGS went up in 2011 because the analysis bottleneck is the culprit.”  My take on that is that in clinical NGS, the all-in $1,000 genome might be postponed to beyond 2014 by perhaps a few more years.

Ion Torrent Launches $1,000 Genome Sequencer in SF

On January 10, 2012, San Francisco, The Ruby Skye nightclub — just a block from the 30th Annual J.P.Morgan Healthcare Conference.

Life Technologies‘ Ion Torrent division hosted a reception and gave a product launch presentation for their new genome sequencer, The Ion Proton.  The invited guests enjoyed a cocktail reception for about 45 minutes before taking their seats at the theater-like presentation space.

Greg Lucier, Life’s CEO appeared, made some opening remarks and introduced Dr. Jonathan Rothberg, Ion Torrant’s founder.  Jonathan spoke for about thirty minutes and recapped the history of Sanger sequencing, 454 sequencing, comparisons to advancements in the computer industry and how his son got him to think about semiconductor-based sequencing.  He explained the rationale for using semiconductor technology for the Ion Torrent sequencer. Rothberg said that using the Ion Personal Genome Machine (PGM) to quickly sequence the genome of the virulent e.coli strain found in a contaminated food outbreak that killed 50 in Germany last year demonstrated the value of the PGM for public health. He said that as a result of the e.coli outbreak experience, Ion Torrent developed assays that turned out to be ideal for healthcare research applications.

At this point, Jonathan stepped back to a black draped structure at the back of the stage and unveiled a rack containing four new benchtop Ion Proton genome sequencers.  Rothberg spent about ten minutes explaining the key details about the new Ion Proton machine.  Life Technnologies is taking orders for the the Ion Proton, which sells for $149,000. He said that these machines are ideal for customers that need to sequence exomes and genomes.  The machines are designed to sequence exomes for $500 and genomes for $1,000 in 24 hours. The costs mentioned are material costs. The Ion Proton uses two new chips.  The Proton I chip has 10X the density of the current 318 chip (1.65 million wells) used in the PGM, is for exome sequencing and will be available later in the Spring. The Proton II chip has even higher density, with about 660 million wells, is for genome sequencing and will be available later in 2012.  Jonathan said that he was impressed that at a starting point of just using the PGM chemistry kit, the Ion Proton produced 200 base pairs of sequence.

Greg Lucier and Jonathan Rothberg on stage with Four Ion Protons

After the presentation, I had an opportunity to see and touch the new Ion Proton machine located at the back of the reception area and spoke with the Director of Product Marketing who was there to demo some of the new machine’s key features.  He said that Life Technologies was taking its sequencers on the road in their new Ion Torrent Bus which was parked out front.  After our discussion, I went outside and climbed aboard their mobile sequencing lab in a bus.  The two spokeswomen there said that bus the has two PGM machines and will soon be outfitted with two Ion Proton sequencers for a total of four machines that can sequence DNA as they drive.  I asked if they would be visiting the upcomimg genome conference at Marco Island.  They said yes and would also be visiting universities and commercial centers.

Pros and Cons of Sharing Personal Genomes on Social Media

I recently particpated in an online conference session held by NGS Leaders when CHI held its Beyond Sequencing conference in San Francisco recently on June 21, 2011. The session was moderated by NGSLeaders’ Eric Glazer and a panel of NGS experts.  The panelists included Kevin Davies, PhD.(Bio-IT World) Pillar Ossorio , PhD. (Univ. of Wisconsin), Johnathan Eisen, PhD, (UC Davis), and Kamamiesh (Kam) Patel, PhD. (Sandia National Labs).  This panel session was about “When People Share Their Genomes on Facebook.”  Both Kevin and Kam participated by telephone and the others were with a live audience in the meeting room.  The session used WebEx to link remote participants.

Kevin summarized the recent history of personal genomics services since the field was started by 23andme.com and deCode Genomics.  He pointed out that these services were marketed as services that enabled consumers to learn much about their genetic make up.  The services just provide information that might help people learn more about their risk for common disease or for geneology.  The customers’ genetic information is not to be used as a diagnostic. While the technology is initially based on microarrays and SNPs, some companies hoped to use NGS when the cost gets low enough.  However, Kevin said that the future of personal genomics is still in the hands of the FDA to decide on guidance to the industry.  Johnathan predicted that we will see a lot of push inside of genomes and personal microbiomes.  Microbiomes are the total kinds of microscopic things that live in or on our bodies.

As the discussion turned to social media, Kam said that the social media giants have big potential uses for health information.  A person could meet with their doctor, then the doctor could later access the person’s Facebook page and follow the progress of a treatment regimen.  But there are pros and cons to watch out for such as exploiters and cost issues.

Johnathan spoke about ‘crowd sourcing’ would be useful for health information.  He said that Facebook is only partly open.  He noticed a new push for open science such as to post lab notebooks on a social media site.  As for citizen science, he predicted that personal genomics, open science projects and citizen science will merge together.  When that happensm then anybody can make or use the information for their own open science projects.

A big question is who owns the personal genetic information held on social media sites.  Pillar, a lawyer, said that  we can think about this in terms of copyrights and patents.  She said that for example, when I get genetic information, I might just get a license for personal use, — it might be limited or unlimited.  The media site rules migth determine who can use the information, etc. At least we have the GINA law to protect our rights regarding employment and insurance discrimation.  However, she thinks that much of this is unknowns.  Pilliar said that the courts would likely say that if you put your genetic information on a public social media site, you are effectively giving away information to the public domain.  She said that people need to be educated about the subject so people would know who should participate.  She said that George Church has a screening process to weed out ignorant people.  He makes applicants take a genomics class and his program has a high cost.

Eric asked the panel when might clinical use will happen or become routine.  Johnathan said that technology will happen soon, but he did not know when clinical practice will happen.  Kevin said that the clinical use of personal genomics is happening now and cited the case of the boy from Wisconsin who was helped by NGS based diagnostics.  He said that there is a huge amount of genetic medical education that is needed.  Pillar said that she believes that the clinical context will take some time to work out.  My take on personal genomics and social media is that we are still in the early early days.