DEVELOPMENT OF A REFERENCE SET OF MICROBIAL GENOME SEQUENCES AND PRELIMINARY CHARACTERIZATION OF THE HUMAN MICROBIOME
ELUCIDATION OF THE RELATIONSHIP BETWEEN DISEASE AND CHANGES IN THE HUMAN MICROBIOME
- This initiative will begin with the sequencing of up to 600 genomes from both cultured and uncultured bacteria, plus several non-bacterial microbes. Combined with existing and other currently planned efforts, the total reference collection should reach over 1000 genomes.
- The initiative will continue with metagenomic analysis to characterize the complexity of microbial communities at individual body sites, and to determine whether there is a core microbiome at each site. Pilot studies will implement shallow and then deep 16S rRNA sequencing, progressing into deep metagenomic sequencing. Several body sites will be studied, including the gastrointestinal and female urogenital tracts, oral cavity, naso-pharyngeal tract, and skin.
- For more information and updates on this component of the project, visit http://www.hmpdacc.org
The second initiative includes a set of demonstration projects to determine the relationship between human health and changes in the human microbiome. The initiative will be implemented by investigator-initiated projects that can leverage the advances of the Human Microbiome Project to examine the relationship between changes in the human microbiome and diseases of interest.
DEVELOPMENT OF NEW TECHNOLOGIES FOR COMPUTATIONAL ANALYSIS
Taking full advantage of the decreased cost of sequencing to improve our knowledge of the human microbiome will require advances in microbial genomics technologies. The ability to generate whole genome sequences is currently limited to the relatively small class of microbes that can be cultured. In order to maximize the number of sequences available in the reference set, new techniques must be developed to culture or otherwise isolate for analysis currently unculturable organisms. In the long-term, methods for sequencing individual microbes or otherwise analyzing all of the members of complex populations will substantively advance this field.
DEVELOPMENT OF NEW TOOLS FOR COMPUTATIONAL ANALYSIS
The data sets produced by metagenomic sequencing and related components will be very large and complex, requiring novel analytical tools for distilling useful information from vast amounts of sequence data, functional genomic data and subject metadata. In addition, if next generation sequencing platforms are used, they will produce large quantities of sequence data that will need new analysis methods.
ESTABLISHMENT OF A DATA ANALYSIS AND COORDINATING CENTER (DACC)
The DACC will be a resource to find information about the project, along with its results and conclusions. Since the HMP, as a community resource project, is committed to rapid data release, the DACC will prove invaluable for coordination of data access and analysis. The DACC will have several specific functions:
ESTABLISHMENT OF RESEARCH REPOSITORIES
- Track, store and distribute raw data, metadata and processed data
- Coordinate data analyses
- Develop data retrieval tools for the research community
- Coordinate development of metadata standards
- Establish a portal to display activities of international projects
Repositories are needed to store materials and reagents generated under the HMP including:
- Cultured organisms
- Amplified DNA from uncultured organisms
- Metagenomic DNA samples
The repositories aim to make resources widely available to the scientific community at a reasonable cost and provide a newsletter to inform sample donors and interested members of the lay public about on-going project progress.
To order an HMP reference strain please visit http://www.beiresources.org/
EXAMINATION OF THE ETHICAL, LEGAL AND SOCIAL IMPLICATIONS (ELSI) OF HMP RESEARCH
The ethical, legal and social implications of HMP research will be studied including:
- Clinical and health implications (e.g. probiotic use)
- Potential forensic uses of microbiome profiles
- Bioterrorism and biodefense applications
- Uses of new technology driven by the HMP
- Ownership of one's own microbiome and privacy issues
EVALUATION OF MULTI-‘OMIC DATA IN UNDERSTANDING THE HUMAN MICROBIOME’S ROLE IN HEALTH AND DISEASE
This initiative seeks to
- Generate microbiome taxonomic, metagenomic and functional data from clinical biospecimens obtained from a cohort(s) of carefully-phenotyped subjects with a specific disease or health state.
- Combine the microbiome and host data to produce a community resource.
The long-term objective of this initiative is to develop a dataset that the community can utilize to explore whether study of the human microbiome beyond sequenced-based analyses will yield important new insights in understanding human health and disease.
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