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An integrated metagenomics pipeline for strain profiling reveals novel patterns of bacterial transmission and biogeography

10/18/2016
Strain-level genetic differences within bacterial species yield new insights into mother-infant microbiomes 
E. coli

Genetic diversity within a bacterial species, such as in Escherichia coli(shown here), can be captured by sequencing microbial communities and MIDAS. Credit: National Institute of Allergy and Infectious Diseases, NIH


October 18, 2016 - Direct microbial sequencing of environmental samples, such as from ocean water, hospital surfaces, and the human gut, have illuminated the vast number of microbes present in our world. However, a microbial species can be genetically diverse, and this variability is often not captured during metagenomic analysis. In a study published online today in Genome Research, scientists developed a new tool to examine genetic differences within bacterial species and uncover novel transmission patterns in mother-infant microbiomes and marine metagenomes not previously appreciated by species-level analyses.

Within a given bacterial species, gene content can vary by 50% or more from the reference genome. "This suggests massive variability at the strain level that could have real functional consequences," said senior author Katherine Pollard, PhD, from the Gladstone Institutes and the University of California, San Francisco (UCSF). "We saw a need for a computationally efficient tool to quantify this variation from shotgun metagenomics data."

The researchers developed the tool, MIDAS, for rapidly profiling differences in gene content and single nucleotide variants across bacterial strains. To build MIDAS, researchers first generated a database of 31,007 high-quality bacterial genomes. Using a set of 30 informative "universal" genes, they hierarchically clustered the genomes to define species. The researchers were able to assign 8.6% of the previously unannotated genomes to a species, and reassigned species for 9.8%.

Applying MIDAS to 98 mother and infant stool metagenomes, the researchers found that the similarity between mother and infant microbiomes has been largely overestimated.

"Strain-level variants reveal patterns that contradict what one would assume from patterns at the species level," said Pollard. Previous studies suggested that mother and infant microbiomes become more similar over the first year of life. However, by examining "marker alleles," or rare genetic differences unique to the mother's strain, the researchers found that very few strains are transferred from the mother but rather are likely acquired from the environment. "The maturation of the infant gut microbiome over the first year gives the impression of ongoing transmissions from the mother," said Pollard. "But the genetic variants in the bacteria show that the acquired strains are not the same as the mother's."

The researchers also applied MIDAS to marine samples collected at varying depths across the world's oceans. The most prevalent marine bacteria had differences in gene content that were associated with geography, and these differences were not detected by species-level analysis. Additional work will be needed to distinguish whether genetic differences between locations are the result of adaptation or genetic drift within the species. "The next big challenge is to disentangle the forces that drive population structure in the microbiome and to associate this variability with traits of the host or environment," Pollard said.

Researchers from Gladstone and UCSF contributed to this work. The study was funded by the National Science Foundation, the Gordon & Betty Moore Foundation, the San Simeon Fund, and the Gladstone Institutes.

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Media Contacts:

The authors are available for more information by contacting: Dana Smith, Communications and Media Relations Specialist, Gladstone Institutes (; +1-415-734-2532).

Interested reporters may obtain copies of the manuscript via email from Dana Macciola, Administrative Assistant, Genome Research (macciol@cshl.edu, +1-516-422-4012).

The manuscript will be published online ahead of print on 18 October 2016. Its full citation is as follows:
Nayfach S, Rodriguez-Mueller B, Garud N, Pollard KS. An integrated metagenomics pipeline for strain profiling reveals novel patterns of bacterial transmission and biogeography. Genome Res doi: 10.1101/gr.201863.115

About Genome Research:

Launched in 1995, Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.

About Cold Spring Harbor Laboratory Press:
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Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. The Press is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit our website at http://cshlpress.org/

Genome Research issues press releases to highlight significant research studies that are published in the journal.



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