Metagenomic binning and association of plasmids with bacterial host genomes using DNA methylation.
Beaulaurier J, Zhu S, Deikus G, Mogno I, Zhang XS, Davis-Richardson A, Canepa R, Triplett EW, Faith JJ, Sebra R, Schadt EE, Fang G
Nat Biotechnol. Dec 2017. doi: 10.1038/nbt.4037
COMMENT: Shotgun metagenomics analysis provide sequence data of all the genetic content present in a given microbiome (not only of a particular tag sequence like in 16S based analysis) allowing the characterization of complete bacterial chromosomes, plasmids and phages. However, given sequencing technology limitations, shotgun metagenomics data can not completely resolve whole genomes so computational methods are applied to assign reads and assembled contigs into 'genome bins'. The obtained 'genome bins' can then be considered as a genome in further analysis.
Sequence based binning can not distinguish between closely related species so binning strategies based solely on this kind of methods might lead to mis-assignments of reads and contigs to the genome bins.
It is known and described that bacterial genomes are methylated in a species and even strain specific manner. Thus, this endogenous epigenetic barcode can then be used for the reads and assembly binning.
The authors describe a method for the use of methylation markers to guide the genome binning. The methylation data is obtained with the PacBio sequencing technology. The method is validated on synthetic and real microbiome samples and it is proven to be valid not only for the genome binning but also to link plasmids and other mobile genetic elements to their host species.