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Home Current Topics Focus for Sequencing Consortium: Select Agents, Microbial Forensics
Focus for Sequencing Consortium: Select Agents, Microbial Forensics Print E-mail
Federal agencies now sponsor a broad variety of microbial genomic sequencing programs, making it difficult to keep up with their progress. Here is a look at one of them, launched in 2009 and targeting select agents, that is, pathogens which could be used by terrorists as weapons.  This program involves five-year contracts to three institutions, with resources totaling more than $106 million, according to officials from the National Institute of Allergy and Infectious Diseases (NIAID), the federal sponsor. The awards went to the Broad Institute in Cambridge, Mass., the J. Craig Venter Institute (JCVI) in Rockville, Md., and the Institute for Genome Science (IGS) at the University of Maryland School of Medicine in Baltimore. Each of these institutes is designated a Genomic Sequencing Center for Infectious Diseases (GSCID), and together they form a consortium. The Broad Institute and JCVI each received $43.3 million, and the IGS, $20 million.

"The focus . . . is to develop organism- specific genomic resources and improve the sequencing and analysis tools needed for microbial forensics and emerging disease research," says William C. Nierman, who codirects the GSCID at JCVI. "The GSCIDs are also researching the use of large-scale genomic and transcriptomic sequencing to expand the understanding of virulence factors and host response to infection," adds Bruce Birren, who directs the Broad Institute GSCID. The longer-term goal is to develop new diagnostics, vaccines, and drugs.

The pace of work within the consortium is brisk. For example, one group recently completed the genomic sequence of the bacterium responsible for causing plague, Yersinia pestis, according to Nierman. A key finding from this project is that redundant and overlapping analytic approaches are needed to assure sequencing accuracy and correct for the shortcomings of specific sequencing platforms and informatics tools, he says.

In a related project, IGS Director Claire Fraser-Liggett, other researchers there, and their collaborators at several other institutions compared a series of Y. pestis genomes, confirming that this bacterial species is most genetically diverse in and around China, where it likely originated more than 2,600 years ago. "The GSCID-funded sequencing of additional plague genomes was crucial in identifying subtle, yet important genomic differences," says Mark Eppinger, co-lead author of that study. All the U.S. Y. pestis isolates appear to stem from a single import of infected rats traveling on a merchant ship from Hong Kong that arrived in San Francisco in 1899, he notes. (See the November 1, 2010, Nature Genetics for details.)

JCVI scientists and those at Walter Reed Army Medical Center in Washington, D.C., are collaborating to sequence genomes from strains of wound-associated Acinetobacter baumannii that infect U.S. soldiers returning from Iraq and Afghanistan, according to Nierman. Separately, researchers from the consortium and other institutions recently analyzed the genome sequence of the southern house mosquito, Culex quinquefasciatus, which is a vector for the West Nile and St. Louis encephalitis viruses as well as the nematodes that cause lymphatic filariasis. (Findings appear in the 1 October 2010 Science.)

The three centers are planning a new round of projects, according to Nierman. These include developing tools and performing analysis across numerous sequenced microbial genomes for both core and pan genome definitions; eukaryotic gene model definitions using RNA sequencing; associating genome sequence variations with virulence and other phenotypic differences; and analyzing the seasonal evolution and diversity of viral pathogens, including the influenza virus. Notably, the JCVI has already generated sequence data for more than 75% of all influenza genomes (_6,000) and made them available in public databases.

Investigators are encouraged to collaborate with GSCID scientists; the process begins by submitting proposals to NIAID (http://www.niaid.nih.gov/labsandresources/resources/gsc/pages/data.aspx).

More information on research on select agents and emerging pathogens will be presented at the 9th Annual ASM Biodefense and Emerging Diseases Research Meeting, which will be held on 6-9 February in Washington, D.C. See http://www.asm.org for details.

Marcia Stone