April journal club: genomes from metagenomes.

Research into the composition and effect that the human microbiome can have on its host has advanced significantly with the application of 16S rRNA gene sequencing techniques and improvements in next generation sequencing technology. Using this marker gene, we can get a pretty good picture of “who” is there using standard, easy-to-use techniques.

However, in order to move forward with mechanistic, functional research, we need to know more than the coarse outline of the bacteria that are present in these communities. First, 16S studies only allow for the identification of the bacterial portion of the microbiome (though we have looked at ways of assessing fungal communities as well in past JCs). Additionally, 16S sequencing does not have the ability to differentiate between bacterial strains, and at the length that most high-throughput methods are currently optimized for, sequencing of specific regions of the 16S rRNA gene generally can only identify bacteria accurately to the genus level.

Inevitable advances in the biology and sequencing will improve 16S sequencing in the coming years; however, another interesting avenue for studying the composition of the (human) microbiome is by whole genome shotgun metagenomics. This method is advantageous in that they give us more biological information about a sample by identifying the genes that are present, and non-bacterial components such as viruses, phage, and fungi. However, if we do not have the computational tools to be able to re-assemble the metagenomic jigsaw puzzle into individual genomes, mechanistic and functional research will still be difficult.

This Friday, we will be examining a semi-recent paper entitled “Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes” where Nielsen et al. design a bioinformatic approach for sub-dividing the jigsaw puzzle of metagenomics into neat little piles, each representing a genome present within the sample.

Together we’ll investigate:

-the what of this algorithm (for a non-bioinformatic audience): what it is, and how it works to disentangle the input information into pseudo-genomes

-the howhow the authors applied this algorithm to a set of gut microbiome samples from which they identified and assembled 238 microbial genomes

For those who stick around to philosophize over beer, we can discuss the future of metagenomic technologies, how it might interact with 16S sequencing for the microbiome centre-stage, and how algorithms like these could be used to explore the human microbiome further.

Details: I will give a short presentation with discussion Friday, April 1st (no joke) at 3:00pm in HSC-3N10A (just outside of the Farncombe Institute). Following, all are welcome to continue discussions at the Phoenix.

Note: You MUST read the paper! This is a more technical paper than we usually pick, but you must make an honest effort to go through the manuscript to attend HMBJC. Highlight areas you are unsure of, and we’ll go through them together!

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