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Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):9623-9628. doi: 10.1073/pnas.1707009114. Epub 2017 Aug 22.

Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA.

Author information

1
Department of Physics, Stanford University, Stanford, CA 94305.
2
Department of Bioengineering, Stanford University, Stanford, CA 94305.
3
Chan Zuckerberg Biohub, San Francisco, CA 94158.
4
Department of Pediatrics, Stanford University School of Medicine, Stanford University, Stanford, CA 94305.
5
Pediatric Stem Cell Transplantation, Lucille Packard Children's Hospital, Stanford University, Stanford, CA 94305.
6
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305.
7
Metabiota, San Francisco, CA 94104.
8
Global Viral, San Francisco, CA 94104.
9
Department of Bioengineering, Stanford University, Stanford, CA 94305; quake@stanford.edu.
10
Department of Applied Physics, Stanford University, Stanford, CA 94305.

Abstract

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.

KEYWORDS:

biological dark matter; cell-free DNA; metagenomics; microbiome

PMID:
28830999
PMCID:
PMC5594678
DOI:
10.1073/pnas.1707009114
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Conflict of interest statement: N.D.W. is an employee of Metabiota and founder of Global Viral; S.R.Q. is a founder of Karius. M. Kertesz is an employee and founder of Karius, but all work was performed while at Stanford and before he joined the company. All other authors declare no conflict of interest.

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