NGS Leaders Blog

February 1, 2012 

Kevin Davies :  At long last, the agenda for the 2012 Advances in Genome Biology and Technology (AGBT) conference in Marco Island, Florida, has been posted.

Later this month, about 800 genome scientists from academia and industry, along with a cadre of over-dressed financial types, will discuss progress in genome sequencing science, platforms, and software over four days of sessions and after-hours parties.

Originally created a decade ago as an antidote to the increasingly crowded and commercialized GSAC (Genome Sequencing and Analysis Conference), created by Craig Venter, AGBT struggled in the years following 9/11, and the meeting’s academic organizers will admit that its survival owed much to steadfast support from Applied Biosystems.

Once the NGS revolution took hold in 2006, however, the meeting never looked back. It has become the premier meeting spot for the genomics/NGS crowd, cleverly allowing the major vendors opportunities to showcase their latest gadgets without overshadowing the science. Attendance is strictly limited, which makes those places increasingly coveted. And the beachfront venue doesn’t hurt either.

(Ironically, Life Technologies, which recently unveiled the Ion Proton sequencer at the Consumer Electronics Show, is not among the sponsors AGBT this year. Pacific Biosciences is the 2012 meeting’s gold sponsor, though there is sensibly no listing of the firm’s traditional fireworks display, an indulgence that wouldn’t jive with the company’s enforced decision to lay off 130 workers six months ago.)

The three keynote speakers are Lynn Jorde (U. Utah), Rick Myers (Hudson Alpha Institute) and Michel Georges (U. Liege). A notable change is that the final session is now devoted to genome biology, shifting the frequently headline-grabbing new technology presentations to earlier in the program.

Oxford Ahoy  

Chief among those will be the long anticipated scientific debut of Oxford Nanopore (ONT), in the form of chief technology officer Clive Brown, who will be presenting the British company’s progress in single-molecule DNA ‘strand’ sequencing. In a release today, ONT says it plans a commercial launch by the end of this year, having previewed its GridION instrument 12 months ago.

It’s been three years since ONT researchers published a promising proof-of-principle in Nature Nanotechnology, demonstrating the ability of protein nanopores to electrically distinguish the four nucleotides in DNA. In 2009, the same year Illumina made an $18-million investment in the company, I persuaded ONT’s reclusive John Milton to talk about the company’s plans on camera (see the video below). In his talk, Brown will evidently be discussing progress in sequencing single stranded DNA, as was discussed by ONT collaborator Mark Akeson at AGBT last year.

Other agenda highlights (on paper) include:

• European Bioinformatics Institute’s Ewan Birney on the ENCODE project
• Heidi Rehm (Partners Healthcare Ctr for Personalized Genetics Medicine) on large-scale clinical sequencing
• Darrell Dinwiddie (Mercy Children’s Hospital) on the roll-out of an NGS-based test for more than 600 severe childhood genetic disorders
• Stephan Schuster (Penn State), who helped sequence Archbishop Desmond Tutu, discusses the genomes of other historic figures
• Mark Adams, a long-time Venter associate at TIGR and Celera now back at the Venter Institute, opens the tutorial sequencing workshop
• Back-to-back presentations showcasing the two leading desktop sequencing platforms, the MiSeq and Ion Torrent’s Personal Genome Machine, from Illumina’s Geoff Smith and NCI’s Joe Boland, respectively.
• Speaking of desktop sequencers, John Healy discusses start-up GnuBio’s new platform, the iGnuIT 1000 (seriously?!)
• A pair of talks on the use of the Pacific Biosciences single-molecule platform to detect methylation and other epigenetic signatures based on kinetic incorporation data, from Nobel laureate Rich Roberts (New England Biolabs) and CSO Eric Schadt.
• The excellent Yaniv Erlich (Whitehead Institute) on surname leakage from genome datasets

If you weren’t lucky enough to grab a slot, you can follow the fun on Twitter (#AGBT).

January 10, 2012 

Kevin Davies :Researchers at Children’s Hospital in Boston have launched the CLARITY Challenge - a $25,000 competition intended to set and advance standards for clinical genomic analysis and interpretation.

CLARITY stands for Children’s Leadership Award for the Reliable Interpretation and appropriate Transmission of Your genomic information. While the much publicized Archon X PRIZE presented by Medco will offer $10 million in prize money for essentially reaching the $1,000 genome early next year, the CLARITY contest focuses squarely on best practices in clinical genome interpretation and data delivery. The winning team will receive a $25,000 prize underwritten by Children's Hospital

The competition is open to academic and commercial researchers worldwide, with applications due no later than March 1, 2012. For logistical reasons, a maximum of 20 teams will be selected to participate in the competition. The winner of the competition, chosen by a panel of seven judges, will be announced in October 2012.

Industry partners include Life Technologies, which raised the prospect of a $1,000 genome in 2013 with the unveiling of its Ion Proton sequencer last week, and Complete Genomics.

“With the swift decline in the cost of sequencing, the time is rapidly approaching when genomic information will leap from the research bench to the doctor’s office and become a part of everyday care,” said Isaac Kohane, director of Children’s Hospital Boston’s informatics program and one of three competition co-organizers.

Coming Together   

Kohane told Bio-IT World that the idea for launching the contest emerged from the success his group enjoyed in running challenges for i2b2 (informatics for integrating biology & the bedside), focused on making data widely available. “The competitive aspect was nice, adds some spice, but [more importantly] it catalyzes teams coming together. I think that there’s a certain social process around these competitions, creating teams for a purpose that otherwise didn’t exist.”

In addition to helping the patients and their families, Kohane hopes to identify and bring together the best elements of competing pipelines, as he expects that there will be stronger and weaker components for each pipeline. “There’ll be one overall winner, but separate and transparent grading of different components of the pipelines.”

“Clearly, we’re going to need teams” to tackle the challenges of clinical genome interpretation, he says. “One of my favorite publications in 2011 was a paper in Nature Biotechnology from Mike Snyder and colleagues, in which they compared Complete Genomics sequence data to Illumina. They found that there was [only a] 93% concordance for single nucleotide polymorphisms (SNPs), which is terrible! And on copy number variants (CNVs), only 24% concordance. That tells me that every point in the pipeline -- from measurement to assembly to annotation, interpretation and generation of reports – all those points are, to be kind, open for improvement.”

The best way to stimulate “a public and transparent improvement of that pipeline” is to compare them side by side, he says, not only for the Consumer Reports-style value but also “to promote best practices in different pipelines, so they can be adopted and shared.”

Three pediatric patients at the Manton Center have been selected, including two with neuromuscular disorders. In each case, doctors strongly suspect a genetic basis for the childrens’ conditions, but “despite the best efforts of clinical geneticists at several sites, the genetic lesion has yet to be identified,” says Kohane.

Manton Center director Alan Beggs recruited the three families taking part. “Their response ranged from enthusiastic and very excited to cautiously optimistic,” says Kohane. Getting IRB approval from Children’s Hospital was tough, he says, in part because of the data sharing requirements.

Each patient and their parents will be sequenced. Life Technologies will sequence the exomes of each volunteer, while Complete Genomics will do whole genome sequencing.

“The project underscores Complete Genomics’ commitment to, and the industry’s path towards, using high quality, accurate genomic information from whole-genome sequencing (WGS) to improve patient care,” said Complete Genomics CEO Clifford Reid. “Through this CLARITY Challenge, we anticipate the discovery of the genetic basis of the children’s unknown disorders and also the creation of best practices for interpreting and presenting actionable results to physicians, patients and their families.”

Judge and Jury 

The seven judges were chosen for their expertise in different parts of the pipeline. They are: Russ Altman (Stanford), Elaine Lyon (ARUP Labs), Joseph Majzoub (Children’s Hospital), David McCallie Jr (Cerner Medical Informatics Institute), Peter Neupert (Microsoft Health Solutions Group), Peter Szolovits (MIT) and Hunt Willard (Duke University).

Among the questions they will be asking: Is the assembly done well? Are the annotations credible? Does the report look readable? Does it make clinical sense? “Not inconsequentially, for a medical director, can they understand the link between the report and the original data? For example, the details of a CNV algorithm are not always transparent to the clinical end user,” says Kohane.

Kohane praises the progress made by a handful of genomics groups in annotating medical genomes, including the work of the team at the Medical College of Wisconsin. “They all did a terrific job, heroic efforts – from the publications, it seems evident they’ve used lots of computation and inspiration and knowledge of the disease(s). What’s not clear is that the effort could be generalized, across a large number of diseases. We’ve seen panels of experts working hard to help one patient using everything they had, where much of it is in their head.”

Children’s Hospital staff note a number of potential pitfalls to be overcome by the contesting teams, including:

- Inconsistent or non-specific sequencing results and non-interoperable processes
- Conflicting gene variant annotations and classification
- A hodge-podge of non-standardized databases
- Lack of standards concerning individual privacy and data access
- Resulting reports that are not clear or useful to doctors, genetic counselors and patients

Full information about the CLARITY Challenge is available at: http://www.childrenshospital.org/CLARITY 

 January 10, 2012 

Kevin Davies : 

In its blog, The Spittoon, 23andMe recently posted a Top Ten list of the consumer genomics firm’s favorite research papers of 2011 

Not surprisingly, the selections focus on the plethora of genome-wide association studies (GWAS) that still dominate many of the leading genetics journals. 23andMe’s top choice just happened to be one of its own papers, but I wouldn’t quibble with that decision too much.

Last summer in PLoS Genetics, 23andMe researchers published a paper mapping two novel risk genes for Parkinson’s disease by mining data on thousands of Parkinson’s sufferers among its 125,000 customers. The 23andMe strategy flips traditional GWAS on its head: rather than select thousands of individuals with a particular disorder and then perform a GWAS, 23andMe performs the genotyping first on its full database, and then stratifies by disease. It is groundbreaking science like this that serves as a swift rebuttal to those who insist on maligning the consumer genomics company as merely “recreational genomics."

What if we broaden the criteria slightly and consider papers focusing on NGS? Of the papers that stood out to me, several focused on the introduction of exome and genome sequencing and analysis in the clinic. Pride of place goes to the landmark report in Genetics in Medicine by Elizabeth Worthey, Howie Jacob and colleagues at the Medical College of Wisconsin in ending the diagnostic odyssey surrounding Nicholas Volker, a 7-year-old boy with a mysterious intestinal disorder who was successfully treated following the discovery of a rare genetic mutation. The peer review paper was formally published in 2011, a couple of months after a Pulitzer Prize-winning series of articles ran in the Milwaukee Journal Sentinel. 

Two papers in the Journal of the American Medical Association from the Washington University team led by Timothy Ley, Elaine Mardis and Richard Wilson illustrated the potential of whole-genome sequencing analysis in cancer patients. One revealed a cryptic fusion oncogene in a patient with acute promyelocytic leukemia with therapeutic implications; the other identified a novel p53 mutation in a patient with increased cancer susceptibility. 

Also of note was the sequencing of a pair of teenage twins with Dopa-responsive dystonia, by Matthew Bainbridge, Richard Gibbs and colleagues at the Baylor College of Medicine that pinpointed the causative gene mutation, and was published in Science Translational Medicine. 

From China, BGI published twenty NGS papers in 2011, including the genomes of the naked mole rat and the hybrid Escherichia coli strain responsible for several fatalities in a food poisoning outbreak in Germany last summer.

So what were your favorite, most impressive NGS papers of 2011?

Editor’s Note: Richard Holland is chief business officer and co-founder of Eagle Genomics Ltd, a UK-based bioinformatics services company that is partnering with the Pistoia Alliance to administer the Sequence Squeeze competition. 

January 6, 2012

Richard Holland : Capitalizing on next-generation sequencing requires as much attention to technology and computer science as life science. The biggest players in the life sciences have also realized that no one will get ahead by “going it alone.” Instead, they are working together pre-competitively to develop open solutions that will benefit the entire industry. The Pistoia Alliance has succeeded in building a unique coalition of industry players - the world’s top pharma companies, life science information, services, and technology suppliers, and academic researchers - to resolve common barriers to R&D innovation, such as the handling of “big data”.

An exciting example of a Pistoia Alliance-led project of particular interest to the NGS community is the Pistoia Alliance Sequence Squeeze Competition, which will award a $15,000 cash prize to the developer of the best new, open-source algorithm for compressing NGS data.

Currently available compression technologies, which enable labs to store data from sequencing runs, are faltering under the data volumes produced by NGS. Pistoia Alliance members recognize that compression solutions may well come from computer scientists or mathematicians - hence the Alliance’s willingness to put forward a generous monetary incentive to encourage anyone to develop a better algorithm.

The judging panel further highlights the importance of this issue to the sequencing community: BGI, the Broad Institute, and the Wellcome Trust Sanger Institute have all put forward staff to judge the competition.

The competition is open to ANYONE, because it recognizes that life scientists may not necessarily have the expertise to resolve this “big data” problem. The answer may lie in statistics, mathematics, computer science, physics, or other non-biological disciplines, so the Alliance is spreading the word as widely as possible in order to encourage entries from previously untapped sources.

Entries can be submitted via the contest website at http://www.sequencesqueeze.org, which also contains details of the functional requirements for entries and some sample code to use as a starting point. Judging of entries takes place within the Amazon EC2 cloud and so we require entries to be submitted using Amazon's S3 file system.

As an incentive to have a go and enter the contest, Amazon is generously offering the first 40 entrants a $20 voucher for use with their cloud services. The competition closes to new entries at 5:00 pm GMT on March 15, 2012. Winners will be announced at the Pistoia Alliance Conference in Boston on April 24, 2012 (held in conjunction with this year’s Bio-IT World Conference & Expo).

The Sequence Squeeze Competition is just one of the projects the Pistoia Alliance is sponsoring. We also have an active effort underway to develop shared cloud services for storing and analyzing NGS data, which we call Sequence Services. The Alliance website at http://www.pistoiaalliance.org has full details of this and other ongoing projects.

December 14, 2011  

Kevin Davies :  Last week’s NGS Leaders webinar on De Novo Assembly of Complex Plant and Animal Genomes prompted more than 300 scientists and informaticians to pre-register, which speaks to the ubiquity and challenge of assembly complex genomes using short reads. Our three speakers – Mario Caccamo (The Genome Analysis Centre, UK), Ian Korf (UC Davis) and Jeffrey Rosenfeld (UMDNJ), outlined several key pointers in tackling complex genome assembly.

“Every genome has its own story in terms of repeats,” says Ian Korf, associate director of bioinformatics at the University of California Davis Genome Center. Korf is one of the principal organizers of  the Assemblathon - a competition to identify best practices in the de novo assembly of complex plant and animal genomes.

Results of the first phase of the Assemblathon were recently published in Genome Research. You can also read more about the Assemblathon at Bio-IT World.

“Every genome is a complex genome - even the simpler ones are pretty complex. There’s no easy genome,” said Korf.

The Assemblathon participants – 17 groups in all - were challenged to assemble a synthetic chromosome of some 96 million bases. Commenting on the results, Korf said: “A lot did a pretty good job, but it’s more difficult to assemble regions with more mutations, so the coding regions were assembled better than non-coding regions.”

The assemblies were ranked by various criteria, including contig and scaffold paths, structural and copy number errors. The top five entrants emerged as:

 -Broad Institute (ALLPATHS-LG)
 -BGI (SOAPdenovo)
 -Wellcome Trust Sanger Institute (SGA)
 -DOE Joint Genome Institute (Meraculous)
 -Cold Spring Harbor Lab (Quake, Celera, Bambus2)

Several useful tools emerged, says Korf, but experience in using the tools makes a big difference. “We found that sometimes two groups will use the same assembler, but the group that knows a bit more about the assembler might do a slightly better job. It’s something of an art at this point,” said Korf.

Choose Wisely 

Korf says that wisely choosing the many different parameters involved in de novo genome assembly is difficult and “probably shouldn’t be attempted by amateurs.” He advises inexperienced users to “contact one of the major sequencing centers and get them to help you. Doing it on your own is pretty much guaranteed to give you a sub-optimal assembly… Don’t jump into genome assembly thinking it’s just like any other bioinformatics problem you can hack with some Perl scripts.”

It starts as far upstream as DNA library preparation. “You don’t want to choose the assembler as the last thing you do,” says Korf. “It must be in conjunction with the sequencing technology, how are the libraries made, the full equation. You can’t do it stepwise… So much is dependent on having high quality sequence and making your libraries correctly.”

Another wise move, says Korf, is to perform a pilot project to explore the content and gauge the overall repeat content of the genome in question. “You should do a little homework ahead of time to get an idea of GC content and other factors,” says Korf.

The availability of longer read lengths, such as those produced by the Pacific Biosciences platform, should prove a boost for genome assemblies. “The long reads are fantastic, but the error rate is a bit of an issue,” said Mario Caccamo, head of bioinformatics at TGAC and a fellow co-author of the Assemblathon I report.

But Korf says the PacBio reads can prove very useful in integrating with short read data: “Genome assembly with longer reads will get much, much easier. The game will be completely changed with reads on the order of 10 kilobases.”

Korf believes the NGS community - “super smart people, full of competitive spirit” – will figure out how to use these 3rd-generation technologies. “Right now, they haven’t had enough time to figure out how to put it all together, but they will pretty soon,” he says. “What you’ll get three years from now will be a lot better than today.”

Clearly audience response suggests we revisit this topic in the near future. What NGS-related topics would you like to see presented in a free NGS Leaders webinar?   Email Janine with suggestions.

Editor’s Note: Last week NGS Leaders joined GenomeQuest in hosting an executive workshop at the Sixth Annual Personalized Medicine Conference at Harvard Medical School. In a guest blog post, GenomeQuest's Chief Marketing Officer, Anthony Flynn, provides the following highlights from both the conference and workshop. 

November 15, 2011 

Tony Flynn : Last week, I attended the Personalized Medicine Conference (PMC), moderated by Dr Raju Kucherlapati. It was, yet again, outstanding in terms of quality of content, presenters, and networking. Immediately afterwards, GenomeQuest and NGS Leaders hosted over 30 moderators and Dx executives at a post-conference workshop to immediately exercise and apply the “best ideas” from the Personalized Medicine Conference across six topic areas. Below are my top “takeaways” from the conference and workshop: 

1) 80% say sequencing value will be in “interpretation”
In the case study on “sequencing technology” run by Richard Hamermesh of HBS, the audience was asked:
In 2021, which of the following sequencing segments will be strongest: hardware, consumables, service, or interpretation?
The answer: eighty percent said interpretation. The viewpoint that interpretation of the data will be challenge #1 in personalized medicine was repeated by several presenters, including: Lee Hood of ISB, Stephen Spielberg of the FDA, Dave King of Labcorp, John Nierderhuber of Inova, and Hakan Kakul of Pfizer.

Immediate good news here: I think that we’re getting over the initial fear of the whole-genome sequencing (WGS) “ocean of data." Yes, we’re understanding that WGS is a technology and that we don’t have to digest everything it produces — we can focus on the data of most interest and use.  Just like we don’t have to watch all 800+ TV channels to justify and enjoy cable service, there’s amazing value in “targeted interpretation.” And, over time, we’ll learn more and expand our targets.

2) PM industry integration is happening
In order to take hold, personalized medicine requires a tighter integration of the healthcare pieces — otherwise, benefits won’t accrue to the investors and the new economic wheel won’t turn. Here, I am encouraged as I see a combination of top-down and bottom-up change agents at work.  Industry leaders such as PMC/FDA/VA are proactively creating an environment for motivating and guiding this integration.  And, industry players — including VCs, Dx companies, labs, sequencing vendors and payers — are working amongst themselves to understand and incrementally affect this integration.
(BTW, progress and thoughts on the regulation front: we heard from many Dx leaders that the FDA is open-minded and willing to be led in PM – so meet early and often in the development/approval process.) 

3) Our aim should be squarely on whole-genome sequencing
While the intermediate technologies of gene-panels and whole-exome sequencing will offer substantial rewards and lessons learned, the economies-of-scale and medical revelations granted by WGS justify that our major investments and best minds focus on this final destination.  After all, according to Partners Scientific Director, Scott Weiss, “WGS will render targeted sequencing obsolete in 4 years.”
As breathtaking as the falling cost-curve of sequencing has been in the past decade, I think we’ll be equally awed by sequencing cost and quality improvements in the next few years. Specifically, I believe that the market force of an expanding set of 3rd generation vendors and technologies (over 10 listed in HBS case study) will enable whole new personalized medicine applications and create whole new markets.

4) VCs and Wall Street are becoming increasingly supportive of PM/MDx
I appreciated the inflective thoughts of Brook Byers of Kleiner (“we are entering the early days of PM“) and Amanda Murphy of William Blair (“we’re at an economic peak of uncertainty in PM“).  Byers was most enthused about the Dx side and influenced by long-term, wellness managers and payers. Also indicating enthusiasm are the funding of the above 3rd generation vendors and warming of MDx acquisition activity, including the $.5B acquisition of Clarient by GE Heathcare.

One of the more interesting dynamics as we arc from genomics for drug/disease research to clinical application is the associated pivot from a largely foundation-funded market to a commercial market — aiming to improve and provide economic value to a $5T global healthcare market.  In my opinion, this adjustment to a commercial market is where much of the management challenges and opportunities lie.

5) The industry needs to agree on a global “atlas” of genotype/phenotype database
This is front and center of many thoughtful personalized medicine talks over the past year.  At PMC, I began to see significant movement in this direction: a) organizations planning the integration of genomics with the EHR which will speed genotype/phenotype associations, b) teams structuring phenotype-rich, genotype-enabled clinical trials, and c) a proposal for a standard platform for research labs to establish and share clinical evidence.

6) Much effort/$ should be put into enabling PM at community hospitals 
Gregory Feero of NHGRI thought it worth noting — from a conference operating deep inside HMS — that 95% of healthcare happens outside academic medical centers.  Well played.  One example of progress is the KEW Group, which is building a national network of PM-based community cancer care centers.

7) The Dx industry is preparing its economic case for MDx
On the one hand, Dx informs 70% of medical decisions and MDx holds immense promise for fundamentally improving healthcare.  On the other, Dx amounts to just $40B of the $5T healthcare industry and the assigned skeptic at the conference (artfully played by Dr Ezekiel Emanuel) waged a blistering attack that personalized medicine makes little/no economic sense. What gives?

Clearly, MDx is undervalued in the healthcare industry — our payment system favors therapy/technology over diagnostics/interpretation.  One giant step forward would be to argue the economic case for MDx.  And I foresee the PM coalition and industry preparing two pieces: a holistic, multi-factor economic argument for MDx to spur reimbursement change and the associated decision support to inform day-to-day care.

8) We continue to be guided and inspired by Dr Lee Hood
n accepting his leadership award, Lee Hood offered a wonderful combination of science vision and medical practicality to guide the path forward.  In particular, he was most excited about: a) family-based studies, proven to reduce errors by 70% and shrink solution space by 100x, b) analysis of single cells, and c) system-level considerations and tools required to address the “grand challenge” of personalized medicine (complexity).

 November 2, 2011  

Kevin Davies : A remarkable public-private coalition of universities, medical centers, technology partners and private philanthropists has created the New York Genome Center (NYGC). The center was officially unveiled in a ceremony at Frank Gehry’s ICA Building in Manhattan this morning.

The coalition is a triumph for Nancy Kelley, NYGC’s founding executive director, who made the creation and funding of the center something of a personal quest over the past 15 months, together with Columbia University’s Tom Maniatis and Sloan Kettering Institute director Thomas Kelly.

"When I first talked to Tom Maniatis and Tom Kelly about this, we were operating with a cell phone and a Hotmail account! 12 months later, to have raised $120 million and brought this number of institutions together is really quite extraordinary," said Kelley.

Kelley recently gave Bio-IT World her first in-depth interview about the creation and vision of NYGC. (Excerpts from her interview will also be published in the November/December issue of Bio-IT World.)

"This is one of the most exciting national developments in genomics and medicine," said Richard Gibbs, director of the Baylor College of Medicine Human Genome Sequencing Center. "This new venture will synergize the efforts of some of the nation’s strongest research institutions, most outstanding researchers and vibrant communities. New York will be a new hub of genomics."

"Nancy Kelley and Tom Maniatis have done a remarkable job of bringing the 11 academic institutions together around this shared purpose," Marc Tessier-Lavigne, president of Rockefeller University, told Bio-IT World. "It required vision, determination and keen diplomatic skills to get the leaderships of the different institutions to realize how much more we could accomplish together than in isolation, and then to get everyone to sign on the dotted line."

Tessier-Lavigne continued: "It is a terrific accomplishment in itself, and also provides an important model for cooperation among New York institutions, which will be increasingly important as we work to build the biomedical enterprise in New York City and to attract pharma and biotech companies here."

One of the frst decisions made by NYGC was to select Illumina as its initial sequencing platform. "By choosing Illumina as its next-generation sequencing (NGS) provider, NYGC is showing its commitment to making the vision of revolutionizing personal healthcare a reality," said Jay Flatley, president and CEO of Illumina. "The launch of NYGC ranks as a significant development in advancing the knowledge and understanding of health-related genomics."

Harold Swerdlow, head of sequencing technology at the UK’s Wellcome Trust Sanger Institute, expressed excitement about the arrival of a major genomics hub in his home town. "The coming together of so many great institutions to form the New York Genome Center represents the culmination of a lot of hard work and a clear vision. Nancy and the other founding members should be applauded for this achievement. As one of NYGC's nearest neighbours to the east, we wish them all the success in building a world-class facility."

Also offering congratulations was Spike Willcocks, VP business and corporate development at Oxford Nanopore, a British NGS company. "We are excited that the NYGC team is building an exceptional technology development team as well as building a world class core facility," said Willcocks. "This is the mark of a team seeking to lead with innovation as well as provision of genomics services. We are really looking forward to working with NYGC’s Innovation Center."

The funding for NYGC, which could open as early as March 2012 with a location in central Manhattan almost settled, comes from a variety of public and private sources, including 11 institutional founding members (see below), private philanthropists, founding member companies, technology collaborators, as well as the New York City Economic Development Corporation and the New York City Investment Fund.

Made in Manhattan  

Kelley is a lawyer and commercial real estate developer who spent much of the past two decades working on behalf of biotech and non-profit medical organizations. Several years ago, while working for Alexandria Real Estate, she oversaw the development of the East River Science Park in Manhattan -- three towers, nearly $1 billion and 1 million square feet.

Two years ago, Kelley began working with a client seeking to establish an institute for personalized medicine, discussions that flirted with New York as a possible location. But while that institute did not materialize as originally conceived, Kelley said it "opened up the idea and possibility of introducing a large sequencing operation in New York. Given the fact I’d been working there for ten years and had many long-standing relationships with scientists there, I brought it to New York to see if there was interest… Things developed from there."

Kelley admits there was enormous skepticism around the proposal, but she was undaunted. After consulting with Maniatis and others, she met with representatives from leading New York medical institutions in August 2010. "It started with Columbia, went to Sloan Kettering and Rockefeller University," she recalled. "They enthusiastically endorsed it, to the extent that within 30 days, we had eight institutions putting seed money into a feasibility study." The seed funding was less than $1 million, but enough to get the venture going.

Eventually 11 charter institutions signed on (see below) including Cold Spring Harbor Laboratory and the Jackson Lab from Maine (where Kelley serves on the Board of Trustees). Perhaps the only notable abstention among New York academic organizations is the Albert Einstein College of Medicine of Yeshiva University. A spokesperson told Bio-IT World: "Einstein chose not to join NYGC because we felt it was not the most cost-effective approach to providing our faculty with genome sequencing services."

Kelley says the vision for NYGC is "to achieve transformational results for healthcare and research… For a long time, [New York has] had the leading global institutions in healthcare, but for whatever reason, haven’t always come together to collaborate and leverage that strength. With this enterprise, it will allow them to do that and take their role on the global stage -- as they should be."

At the core of NYGC will be large high-throughput sequencing center, offering services to founding members and other organizations. Much of the research focus will be in bioinformatics. "There’s also the idea of an innovation center that would introduce new technologies that would be utilized throughout New York," she says.

Kelley said getting NYGC off the ground has been "very, very challenging," but the process was helped by institutional leadership "knowing how important this was going to be for New York." Another key factor was the "participatory and collaborative" nature of the process. "That helped everyone feel they were… on the same playing field, no matter what their size," she said.

Many issues inevitably cropped up about the way the center would be governed. "Some institutions stepped back and stepped forward again," says Kelley. "The reasons for hesitation by some Institutions were more organizational than financial. Some of the institutions are in the midst of major building projects and research programs, so [had to ask] whether spending capital in this area was more important to their ongoing operations."

Kelley’s Heroes  

Funding NYGC proved to be a massive undertaking. "There are a number of pieces to the quilt that had to be knit together to be able to put this all together," said Kelley. "One of the strengths of this effort is that its success is not dependent upon one funding source, especially a public funding source, which has proved to be a problem in some other large projects like this one."

Kelley says Maniati played a pivotal role. "He was the first person whom I talked to about this, and has been instrumental at every level in guiding this forward. So we’ve really done this together."

She also praised Kelly and the relatively new leadership at Sloan Kettering and Rockefeller University -- Craig Thompson and Marc Tessier-Lavigne respectively. Russ Carson (Welsh Carson/New York City Investment Fund) "immediately saw the benefits of this to the City," and is now chairman of NYGC’s Board of Directors.

NYGC’s bioinformatics center will be named after the Simons Foundation, the first major philanthropic donor, offering a $20-million matching challenge grant. The Bloomberg Philanthropies have kicked in $2.5 million. In addition to Tony Evnin’s "very significant commitment to the Center," Carson has also pledged what Kelley calls "a very substantial sum of money."

There are two industrial partners – Hoffman La Roche and Illumina. Kelley says both Illumina and Life Technologies were invited to make presentations on how they would partner with NYGC. "In the end, there’s just been enormous progress made by Illumina in their productivity and turnaround times this year, and that proved to be one of the deciding factors," says Kelley.

NYGC expects to launch with 30 next-gen sequencing instruments in its first year. "This will not be an exclusive technology in any way," Kelley noted. "In the Innovation Center, we’ll be testing new technologies and making them available to the scientists in New York."

A search committee (chaired by Evnin) has been assembled to recruit a world-class scientific director. In addition to the sequencing center, serving the founding members, pharma collaborators and hospitals, Kelley says there will be "a very robust bioinformatics presence" and an internal research program.

The Innovation Center will allow scientists to use the facility and develop new technologies and products. A training component is planned in conjunction with Cold Spring Harbor Laboratory and other organizations. And, Kelley said, there will be a small philanthropic unit.

Kelley fully expects there to be a strong clinical component to NYGC. "There will be a CLIA-certified portion of the facility and we’ll be interacting very closely with hospitals like NewYork-Presbyterian Hospital and North Shore-LIJ."

As for Kelley’s future role, she points out that creating the strategic plan and raising the money is only a small component of building a successful institute. "There’s a huge ongoing financial, executive and operational role that has to be put together with a large organization, and I’d expect to play a key role in doing that," she said.

"At one point, Richard Gibbs said something to me: ‘You have to be absolutely fearless to do this.’ He’s right… I don’t think there was one day this year when I had full confidence we’d actually make it, but I knew it was important to try."