Tip of the week: phiGENOME for bacteriophage genome exploration

How many of you remember the first time you saw that phage image in your Bio 100 textbook? You know–the one that had the angular head, the coiled tube, and the spiky leg-looking things? That’s been burned into my memory banks ever since. And to find out that it was just a teeny packet of injectible nucleotides looking for a place to attach…still gives me chills. Couldn’t have been designed better by a sci-fi writer.

And I can remember hearing about them being among the first sequenced entities. Researching this post I went to look back at some of the early sequence literature, and found this figure, which made me laugh out loud. It was a full 1 1/2 page of nucleotides and amino acids for a single gene, from a 1976 paper by Fiers et al:

The last line in this same paper also cracked us up:

The secondary structure of the coat gene resembles a flower, and there are similar foldings in other parts of the molecule; the secondary structure of the whole viral RNA therefore constitutes a bouquet.

Awww….isn’t that significantly less creepy than my image of phages??

The famous position of  lambda phage in helping us to understand many of the first well-studied features of gene regulation was among my earliest memories in college molecular biology classes too. But as sequencing technology ramped up, and the focus turned to bigger and bigger biology, I hadn’t heard much about phage research for a while–I thought of them mostly as tools in my library screens.

But recently in certain discussions of antibiotic resistance I’ve been hearing about them again–and how their properties may be useful tools again to target infection-causing and other unwanted bacteria. In fact, they have a long history of use for this–they pre-dated the antibiotic revolution, but were upstaged by the discovery and development of penicillin and the rest.

So when my recent results from the standing MyNCBI search I have running pointed me to a new bacteriophage resource, I was intrigued. Having had a chance to look at it, I’m really glad to have explored it and to revisited phage biology. The new phiGENOME tool is a very nice item in the bioinformatics arsenal.

phiGENOME is a new addition on to an already existing resource called phiSITE, which is a curated database of cis-regulatory elements in bacteriophages. Currently it contains details about 32 phages and 732 regulatory sites (428 experimentally identified) in total.

But the researchers who developed phiSITE first, and now phiGENOME explain why they needed to create a new browser suited to their specific needs. They considered the others–Ensembl, UCSC, GBrowse, Map Viewer, etc–but those didn’t seem right for their purposes for various reasons, and their paper describes that. To accommodate the many types of bacteriophages, they needed to be flexible–some of these are double-stranded (ds) DNA genomes, some single stranded (ss), some are ds or ss RNA genomes. Some are linear, some are circular. That’s a lot of diversity–and there are just over 600 of them sequenced now (and over 500 are in their viewer at this time). The authors say estimates exist that there are, in fact, 1031 phages actually out there–making them the most abundant biological entities on the planet (yeah, now try to sleep….).

Anyway–their browser had to deal with all of that. So they created a genome viewer that indicates the nature of each one graphically, and provides access to the sequence. Their database of regulation information also enables them to annotate the features with handy color codes on the graphic viewer and on the text-based sequence, and provides additional links to the information. And they have more graphics that enable you to understand the regulatory interactions in further detail.

This tip of the week explores phiGENOME and the visualization options. This fills a nice niche in our collection as the first bacteriophage resource collection, and it’s also the first Slovakian bioinformatics site we can remember highlighting!

Be sure to check out their publications for more detailed information on the background and framework they used to develop this tool. And I contacted the team with questions before I did this, and they assure me they are eager for your feedback on features and functionality that you’d like to see here.  You can contact them from their Help page. Go have a look. It’s not just like every other browser you’ve seen.

Quick links:

phiGENOME: http://www.phisite.org/genome

phiSITE: http://www.phisite.org

List of phage genomes at NCBI: http://www.ncbi.nlm.nih.gov/genomes/genlist.cgi?taxid=10239&type=6&name=Phages

Bacteriophage ecology group: http://www.mansfield.ohio-state.edu/~sabedon/ aka phage.org for some cool images and other phage info.

References:

Fiers, W., Contreras, R., Duerinck, F., Haegeman, G., Iserentant, D., Merregaert, J., Min Jou, W., Molemans, F., Raeymaekers, A., Van den Berghe, A., Volckaert, G., & Ysebaert, M. (1976). Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene Nature, 260 (5551), 500-507 DOI: 10.1038/260500a0

Klucar, L., Stano, M., & Hajduk, M. (2009). phiSITE: database of gene regulation in bacteriophages Nucleic Acids Research, 38 (Database) DOI: 10.1093/nar/gkp911

Stano, M., & Klucar, L. (2011). phiGENOME: An integrative navigation throughout bacteriophage genomes Genomics DOI: 10.1016/j.ygeno.2011.07.004