Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 36, Pages 9623-9628Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1707009114
Keywords
cell-free DNA; microbiome; metagenomics; biological dark matter
Categories
Funding
- US Agency for International Development (USAID) Emerging Pandemic Threats PREDICT program [GHN-AOO-09-00010-00]
- John Templeton Foundation of the Boundaries of Life Initiative [51250]
- Bill and Melinda Gates Foundation
- March of Dimes Prematurity Research Center at Stanford University
- Stanford Child Health Research Institute
- John Templeton Foundation [51250]
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Blood circulates throughout the human body and contains molecules drawn from virtually every tissue, including the microbes and viruses which colonize the body. Through massive shotgun sequencing of circulating cell-free DNA from the blood, we identified hundreds of new bacteria and viruses which represent previously unidentified members of the human microbiome. Analyzing cumulative sequence data from 1,351 blood samples collected from 188 patients enabled us to assemble 7,190 contiguous regions (contigs) larger than 1 kbp, of which 3,761 are novel with little or no sequence homology in any existing databases. The vast majority of these novel contigs possess coding sequences, and we have validated their existence both by finding their presence in independent experiments and by performing direct PCR amplification. When their nearest neighbors are located in the tree of life, many of the organisms represent entirely novel taxa, showing that microbial diversity within the human body is substantially broader than previously appreciated.
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