Microbiology, Metagenomics and Bioinformatics

Johan Bengtsson-Palme, University of Gothenburg | Wisconsin Institute for Discovery

Browsing Posts tagged Genome sequencing

I proudly announce that today Metaxa has been officially released. Metaxa is a a software tool for automated detection and discrimination among ribosomal small subunit (12S/16S/18S) sequences of archaea, bacteria, eukaryotes, mitochondria, and chloroplasts in metagenomes and environmental sequence datasets. We have been working on Metaxa for quite some time, and it has now been in beta for about two months. However, it seems to be stable enough for public consumption. In addition, the software package is today presented in a talk at the SocBiN conference in Helsinki.

A more thorough post on the rationale behind Metaxa, and how it works will follow when I am not occupied by the SocBiN conference. A paper on Metaxa is to be published in the journal Antonie van Leeuwenhoek. The  software can be downloaded from here.

Assemblathon

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There is currently an interesting competition going on organised by UCSC called the Assemblathon. The idea is that participating research groups will try to assemble simulated short-reads to a simulated genome, with the winner being the group doing it “best” (by some criteria set up by the evaluation team at the UC Davis Genome Center). The complete set of rules can be found here. The whole thing will culminate in a Genome Assembly Workshop at UC Santa Cruz in mid-March.

I think the competition is an interesting initiative, hopefully inspiring new, more efficient, sequence assembly ideas. Those are desperately needed in these times of ever-incresing DNA sequence generation. In addition, there are numerous already existing genome assembly programs, but (as noted on the Assemblathon site) it is not obvious which one is the best in a given situation. Hopefully the competition can shed some light on that too. The deadline for participation is the sixth of February, and even though I am not myself competent enough to participate, I hope the ones who do are successful in their work.

In a recent Nature article (1), Craig Venter and his co-workers at JCVI has not only sequenced one marine bacterium, but 137 different isolates. Their main goal of this study was to better understand the ecology of marine picoplankton in the context of Global Ocean Sampling (GOS) data (2,3). As I see it, there are at least two really interesting things going on here:

First, this is a milestone in sequencing. Were not talking one genome – one article anymore. Were talking one article – 137 new genomes. This vastly raises the bar for any sequencing efforts in the future, but even more importantly, it shifts the focus even further from the actual sequencing to the purpose of the sequencing. One sequenced genome might be interesting enough if it fills a biological knowledge gap, but just sequencing a bacterial strain isn’t worth that much anymore. With the arrival of second- and third-generation sequencing techniques, this development was pretty obvious, but this article is (to my knowledge) the first real proof of that this has finally happened. I expect that five to ten years from now, not sequencing an organism of interest for your research will be viewed as very strange and backwards-looking. “Why didn’t you sequence this?” will be a highly relevant review question for many publications. But also the days when you could write “we here publish for the first time the complete genome sequence of <insert organism name here>” and have that as the central theme for an article will soon be over. Sequencing will simply be reduced to the (valuable) tool it actually is. Which is probably good, as it brings us back to biology again. Articles like this one, where you look at ~200 genomes to investigate ecological questions, are simply providing a more relevant biological perspective than staring at the sequence of one genome in a time when DNA-data is flooding over us.

Second, this is the first (again, to my knowledge) publication where questions arising from metagenomics (2,3,4) has initiated a huge sequencing effort to understand the ecology or the environment to which the metagenome is associated. This highlights a new use of metagenomics as a prospective technique, to mine various environments for interesting features, and then select a few of its inhabitants and look closer at who is responsible for what. With a number of emerging single cell sequencing and visualisation techniques (5,6,7,8) as well as the application of cell sorting approaches to environmental communities (5,9), we can expect metagenomics to play a huge role in organism, strain and protein discovery, but also in determining microbial ecosystem services. Though Venter’s latest article (1) is just a first step towards this new role for metagenomics, it’s a nice example of what (meta)genomics could look like towards the end of this decade, if even not sooner.

  1. Yooseph et al. Genomic and functional adaptation in surface ocean planktonic prokaryotes. Nature (2010) vol. 468 (7320) pp. 60-6
  2. Yooseph et al. The Sorcerer II Global Ocean Sampling expedition: expanding the universe of protein families. Plos Biol (2007) vol. 5 (3) pp. e16
  3. Rusch et al. The Sorcerer II Global Ocean Sampling expedition: northwest Atlantic through eastern tropical Pacific. Plos Biol (2007) vol. 5 (3) pp. e77
  4. Rusch et al. Characterization of Prochlorococcus clades from iron-depleted oceanic regions. Proceedings of the National Academy of Sciences of the United States of America (2010) pp.
  5. Woyke et al. Assembling the marine metagenome, one cell at a time. PLoS ONE (2009) vol. 4 (4) pp. e5299
  6. Woyke et al. One bacterial cell, one complete genome. PLoS ONE (2010) vol. 5 (4) pp. e10314
  7. Moraru et al. GeneFISH – an in situ technique for linking gene presence and cell identity in environmental microorganisms. Environ Microbiol (2010) pp.
  8. Lasken. Genomic DNA amplification by the multiple displacement amplification (MDA) method. Biochem Soc Trans (2009) vol. 37 (Pt 2) pp. 450-3
  9. Mary et al. Metaproteomic and metagenomic analyses of defined oceanic microbial populations using microwave cell fixation and flow cytometric sorting. FEMS microbiology ecology (2010) pp.