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IGS Agenda for 2011 Includes New PacBio Platform, Microbiome Effort

By Alex Philippidis

NEW YORK (GenomeWeb News) – In 2011, the Institute for Genome Sciences at the University of Maryland School of Medicine will take delivery on a new Pacific Biosciences single-molecule, real-time sequencing platform, as well as hire additional faculty and consider how to enhance its computing infrastructure.

"We are looking forward to that arriving in the first quarter of 2011. That may be a little bit too optimistic, but certainly we hope that by April or May it will be here," IGS Director Claire Fraser-Liggett told GenomeWeb Daily News.

In a recent interview about IGS' 2011 plans, she said IGS has secured a five-year microbial genome sequencing contract from the National Institute of Allergy and Infectious Diseases (NIAID). The contract permits infectious disease researchers to submit white papers for review to generate DNA sequence or transcriptome sequence from interesting collections of isolates of high priority pathogens. Each project planned for review can propose one or a combination of platforms, depending on the goals of a project.

"We have a large number of projects that have been approved as part of that, and most of these, I would say, are focusing on looking at one to 200+ isolates of various pathogens of interest," Fraser-Liggett said. "What we're really very excited about is the theoretical ability of the PacBio platform to really revolutionize how quickly we can process those samples and drive down the cost, and increase the speed at which we get data."

According to Fraser-Liggett, that speed would allow IGS to use the remaining time on the contract to "continue to bring in new projects, and get a whole lot more done for a given set of dollars."

She cited a study published earlier this month in the New England Journal of Medicine in which PacBio and Harvard Medical School researchers characterized the bacterial strain from the recent Haitian cholera epidemic. The study's main finding pinpointed the origin of the Haitian cholera strain as being from South Asia, rather than Latin America, and introduced by human activity.

But unlike a team from the US Centers for Disease Control and Prevention, which used DNA fingerprinting to obtain similar results, the PacBio-Harvard Medical collaboration provided a more complete picture of the Haitian cholera strain and its virulence, at relatively modest cost. The study's senior author told GWDN sister publication In Sequence that the age of sequencing-based rapid pathogen analysis may finally have arrived.

"What was also very exciting to me about that paper was that from acquisition of the sample to availability of the data, that all happened in less than 24 hours," Fraser-Liggett said.

The arrival of the PacBio platform, she added, means that IGS will "in all likelihood" start to phase out its Roche 454 platform. While the institute has already shifted the bulk of its sequencing work to its Illumnia HiSeq platform, IGS still uses Roche 454 pyrosequencing technology for some applications.

Most of IGS' research efforts in 2011, she said, will be a continuation "and hopefully some scale-up" of existing projects — in particular a set of both new and continuing projects related to the Human Microbiome Project.

Fraser-Liggett said she will begin a collaboration with Patricia Hibberd at Massachusetts General Hospital to do microbiome characterization in two different sets of patients Hibberd has enrolled in clinical trials to examine the safety of various probiotics — a new effort within the Human Gut Microbiome Initiative.

Another research initiative moving forward, according to Fraser-Liggett, is the University of Maryland effort to create a new division focused on the interaction between the human body and the microbes that inhabit it, using expertise from IGS. The new institute will be within a new research "enterprise" the university is establishing for the study of autoimmune and inflammatory diseases. The enterprise is being funded with UM's largest-ever donation, a $45 million gift from Indiana businessman Ken Cafferty and his wife Sheila.

Fraser-Liggett said creation of the third institute will entail some transfers of UMSOM faculty members to IGS, which is now in the works. That institute will have new space built out on part of the university's Baltimore campus next door to the building that houses IGS, she said, but the space is not likely to be ready for 18 months to two years.

Also next year, IGS will examine how best it can build up its computational infrastructure, in part by taking advantage of existing clouds such as those of Amazon and Google. Fraser-Liggett said several IGS researchers have received National Science Foundation funding to develop interfaces allowing any investigator with a computer terminal to run data analysis on a cloud compared with doing it locally.

"It starts to become very limiting and impractical in terms of thinking about continuing to build computational infrastructure to do some of these largest computes," Fraser-Liggett said, especially when so many next-generation sequencing platforms are available outside of traditional sequencing centers — though many of those venues don't have the computer infrastructure to deal with the torrent of data generated.

Principal investigators involved in the effort are Owen White, director of IGS' bioinformatics department and a professor of epidemiology and public health at UMSOM, and Florian Fricke, a microbial geneticist and assistant professor at IGS' Department for Microbiology and Immunology.

Fricke and White are among UM and IGS researchers who have developed the CloVR virtual machine, which provides push-button pipelines for analysis of microbial genome sequences and runs on a desktop or a cloud. Funding for CloVR's latest version, released Sept. 1, originated with the American Recovery and Reinvestment Act and came to nearly $1.4 million from NIH and about $460,000 from NSF.

The end of ARRA in 2011 is not expected to have a major impact on IGS, since only a handful of research projects were funded through the two-year stimulus measure, Fraser-Liggett added.

IGS has received positive indications over the past three to four months on applications for a combined $14 million in multi-year grant awards, she noted. The institute's volume of current multi-year open grants and contracts stands at $80 million, up from $71 million in the past year — of which IGS generates about $20 million annually.

Fraser-Liggett also said that most of IGS' strategic planning efforts over the last six months have focused on making decisions on additional faculty hires. She said that IGS has developed a short list of candidates for two new faculty positions IGS plans to create in 2011, with expertise in bioinformatics and/or cancer genomics. "We're hoping to have a decision by the spring," she said.

The two hires would add to IGS' current staff of 24 faculty members among 109 total employees. As a result of hiring the new faculty members, who will in turn hire support staffers, IGS expects its workforce to swell to around 125, Lori McKay, IGS senior administrator, told GWDN.

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