ROCKVILLE, Md. and LA JOLLA, Calif., June 13, 2012 /PRNewswire-USNewswire/ -- Researchers from the J. Craig Venter Institute (JCVI) along with members of the National Institutes of Health-funded Human Microbiome Project Consortium (HMP), have published a scientific paper in the journal Nature characterizing the human microbiome, the community of microbes that live in and on the human body. This research, the largest and most comprehensive study done to date on the human microbiome, has revealed an astonishing level of diversity and variety of microbes among the group of 242 healthy individuals. The researchers outlined a set of standardized methods and protocols by which these new human microbiome data and other metagenomic data sets can be readily accessed and analyzed by the scientific community.
This study published last week is part of a large group of coordinated scientific reports published on June 14, 2012, in Nature and several journals in the Public Library of Science (PLoS), by approximately 200 members of the HMP Consortium from nearly 80 multidisciplinary research institutions who are reporting on 5 years of research. HMP, launched in 2007, received $153 million from the NIH Common Fund, a source of funding for high-impact, innovative, trans-NIH research.
Barbara Methe, Ph.D., JCVI professor, was one of the researchers in the Consortium who was actively involved in the Nature paper described here and is also corresponding author on this publication. JCVI researchers were also important contributors to a second HMP Consortium Nature publication describing additional analysis of human microbiome data.
The HMP Consortium also published papers in PloS journals and JCVI researchers are key contributors to these papers. JCVI's Johannes Goll is the first author on a paper in PLoS ONE describing JCVI's large-scale human microbiome analysis tool, METAREP. The key features of and improvements to METAREP are enabling larger and larger datasets to be rapidly and easily analyzed, searched and compared. METAREP was successfully used with the HMP Consortium data analysis enabling more than 400 million genes from 14 billion segments of DNA to be analyzed. METAREP is an example of standardized tools available to the scientific community for their metagenomic research that have been developed by researchers at JCVI.
JCVI's Kelvin Li is first author on another paper in PLoS ONE describing diversity patterns, especially those of low abundant taxa, which represent the majority of genetic diversity in the human microbiome using sequences from the 16S rRNA gene as a biomarker. Li and colleagues determined that the low abundant taxa are not sufficiently quantified with standard ecological measures, which motivated the introduction of a novel statistic ("τ") which couples the ordering of taxonomic abundance with well-known statistical properties of standard deviation to better characterize this low abundant fraction.
JCVI scientists also participated in two additional papers that are part of the HMP Consortium PLoS virtual collection. A PLoS ONE paper (Ward et al.) describes the development of the protocol used by the HMP Consortium to sequence 16S rRNA gene sequences, and a PLoS Computational Biology paper (Abubucker et al.) describes methodology used in HMP data analysis to accurately and efficiently characterize microbial metabolic pathways and functional modules from the human microbiome directly from high-throughput sequencing reads.
According to Dr. Methe, "We are excited by the results of this work since we have long known that uncovering the secrets of the microbes that live in our bodies will undoubtedly lead to more in-depth information about human health and disease. We look forward to continued research with larger and larger groups of patients in the hopes that one day screening of the human microbiome will be a routine part of medical care."
JCVI researchers have a long and successful history of both human genomics and metagenomics research. In addition to the seminal work in sequencing the first draft human genome published in 2001, and sequencing, analysis and publishing the first complete diploid human genome in 2007, JCVI researchers were early pioneers in the human microbiome research. In the early 2000s Drs. Craig Venter and Hamilton Smith were awarded a grant from DARPA to examine the microbes found in the human gut. This work was carried out by researchers including JCVI's Karen Nelson, Ph.D., at The Institute for Genomic Research (TIGR, now part of JCVI) and several other institutions and published in 2006 in Science. This paper in which the researchers found more than 60,000 microbial genes was the first metagenomic description of the microbes residing anywhere on the human body.
In addition to the HMP, JCVI is currently involved in at least 15 other human microbiome studies all related to several aspects of disease and health. The Nature publication today is a follow up to another JCVI/HMP Consortium paper published in Science in 2010 that describes 178 reference microbes associated with the human body.
According to Dr. Nelson, Director of JCVI's Rockville, MD laboratory and head of JCVI's human microbiome research, "We are excited about the new series of papers that will appear this week and look forward to new findings as we expand our research portfolio to look at the human microbial metabolome and proteome in diverse populations. The HMP has presented a solid foundation for these additional follow-up studies."
METHODS AND RESULTS FROM HMP CONSORTIUM NATURE PAPER
The human body contains trillions of microorganisms—out numbering human cells by 10 to one. Because of their small size, however, microorganisms make up only about one to three percent of the body's mass but play a vital role in human health.
To define the normal human microbiome, HMP researchers sampled 242 healthy U.S. volunteers (129 male, 113 female), collecting tissues from 15 body sites in men and 18 body sites in women including three vaginal sites. Researchers collected up to three samples from each volunteer at the mouth, nose, skin (two behind each ear and each inner elbow), and lower intestine via stool samples.
The HMP researchers then purified all human and microbial DNA in each of more than 5,000 samples and sequenced these samples. Using bioinformatic tools, researchers could sort through all 3.5 terabases of genomic data and identify specific signals found only in bacteria – the variable genes of bacterial ribosomal RNA called 16S rRNA – that can identify microbial species. Focusing on this microbial signature allowed HMP researchers to subtract the human genome sequences and analyze only the bacterial DNA. In addition, metagenomic sequencing, or the sequencing all the genes in a microbial community, allowed the researchers to also study the metabolic capabilities encoded in the genes of these microbial communities.
HMP researchers now calculate that more than 10,000 species occupy the human ecosystem, and that they have found between 81 and 99 percent of all the genera of microorganisms in healthy adults. HMP researchers also reported that these microbes contribute more genes responsible for human survival than humans themselves. Where the human genome carries about 22,000 protein-coding genes that carry out metabolic activities, researchers estimate that the microbiome contributes about 8 million unique protein-coding genes or 360-times more bacterial genes than human genes.
In addition, the bacterial genomic contribution is critical for human survival. Genes carried by bacteria in the gastro-intestinal track, for example, allow humans to digest foods and absorb nutrients that otherwise would be unavailable.
The HMP Consortium is managed by National Human Genome Research Institute, in partnership with the NIH Office of the Director, the National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Cancer Institute, National Institute of Dental and Craniofacial Research, and National Institute of Diabetes and Digestive and Kidney Diseases, all part of NIH.
More information about HMP can be found at http://commonfund.nih.gov/hmp/index.aspx. An illustration showing the body sites that were sampled as part of the Human Microbiome Project healthy cohort study is available at: www.genome.gov/pressDisplay.cfm?photoID=20163. More information about the JCVI's work on the human microbiome can be found at: http://www.jcvi.org/cms/research/projects/hms/overview/.
Source: PR Newswire