"Application of Electronic Mapping to Metagenomic Characterization of a Complex Microbial Sample" - ASHG 2017

November 17, 2017

The microbiome is a complex and dynamic mixture of microbes inhabiting many surfaces on and within the human body. While increasing lines of evidence point to the crucial role that these microbes play in maintaining health, disruptions in population compositions also correlate with a variety of diseases. The characterization of microbe populations has historically been limited to known genetic markers of strains such as 16S rRNA genes. More recently, shotgun sequencing has been employed in an attempt to provide a more accurate measure of biodiversity. While whole metagenome sequencing is more comprehensive than single marker typing, short read lengths prevent accurate quantitation of related strains within a mixture as well as consistent characterization of large-scale structural variation that can significantly impact pathogenicity.

To address these issues, Nabsys has applied the HD-MappingTM platform to the identification and quantitation of microbial strains in the context of a single defined complex
sample. HD-Mapping employs fully electronic detection of tagged single DNA molecules, hundreds of kilobases in length, at a resolution superior to existing optical mapping approaches. The preservation of long-range information coupled with superior resolution allows for highly sensitive and specific genome detection and structural characterization.

Nabsys single-molecule reads derived from this complex mixture were mapped to a database of microbial references resulting in identification of strains within the sample. Titrating the relative abundance of a single bacterial genome in a complex sample resulted in quantitation that was linear over 3 orders of magnitude. In addition, assembly of the mixed reads into independent, map-level contigs allowed for the identification and structural comparison of distinct but related strains contained within the same sample.

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