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Weinstock Provides Human Microbiome Project Update at ASM

By Andrea Anderson

SAN DIEGO (GenomeWeb News) – The Human Microbiome Project recently implemented the first data freeze for 16S rRNA sequence data generated from samples of apparently healthy individuals — and plans a similar freeze of shotgun sequence data this summer, according to George Weinstock, associate director of Washington University's Genome Center and an HMP leader.

Speaking at the American Society for Microbiology conference here today, Weinstock said HMP researchers decided to set their initial 16S rRNA sequence data freeze for May 1st of this year, with a shotgun sequence data freeze expected on around July 1st.

The 16S rRNA dataset, which includes Roche 454 sequence information on specific 16S regions for more than 5,000 specimens, is currently making its way through the National Center for Biotechnology Information (NCBI) system, he said. Analysis of the data is ongoing.

As part of the HMP, a National Institutes of Health Roadmap Initiative launched in late 2007, researchers intend to get microbiome information for least 300 individuals with no known health problems sampled at 15 to 18 body sites over two to three visits. Samples from these healthy individuals are being characterized using 16S rRNA, shotgun, and transcriptome sequencing.

So far some 285 individuals have been recruited for that arm of the project, with clinical samples being collected at the Baylor College of Medicine and Washington University, Weinstock said. Those samples are being passed along to sequencing centers at Baylor, WashU, the Broad Institute, and the J. Craig Venter Institute. Of the study participants sampled so far, 166 have returned for a second round of sampling and 28 individuals have been sampled a third time.

"This is going along very well," Weinstock said, explaining that the 16S and upcoming shotgun sequence data freezes reflect HMP members' desire to aid data analysis within the consortium and to make data available to the broader research community.

Preliminary data shows 16S sequence clusters correspond to different body sites, Weinstock explained. For instance, he presented 16S rRNA V3-V5 variable region sequence data on samples from 18 individuals showing clustering of sequences from mouth, skin, nose, stool, and vagina samples.

In addition, the team is seeing some sub-structure within 16S rRNA data at each body site, he added, as well as differences in microbial diversity both at various body sites and when comparing one individual to the next.

Weinstock also outlined progress being made on shotgun sequencing of samples from healthy individuals, noting that HMP researchers are using Illumina 100 base pair, paired-end reads to generate about 10 gigabases of sequence data per specimen, currently targeting 572 specimens from six body sites.

Again, early results from those studies are providing information about the communities found on and in the human body, the stability of these communities over time, and the diversity that exists within and between individuals.

Along with these efforts to gauge the microbial communities associated with healthy individuals, members of the HMP are also characterizing a growing set of reference strains in order to better interpret metagenomic data.

Just last week, members of the HMP Jumpstart Reference Strains Consortium published a paper analyzing the first 178 reference genomes. Weinstock said that team has now sequenced more than 360 reference strains and identified many more both cultured and uncultured microbes that they plan to study through the reference effort.

So while the HMP's goal is to sequence at least 900 reference strains, the total number of strains sequenced may eventually exceed that, he added, noting that some 945 candidates strains for sequencing have been identified.

"I'm hoping we go well beyond this by the time the project is over," Weinstock said.

The HMP also has plans for 15 disease-oriented demonstration projects, along with supporting projects focused on everything from technology development to ethics.

And as the bacterial studies already underway continue to advance, Weinstock noted, HMP researchers are starting to tackle viral and eukaryotic components of human microbiomes.

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