Interesting PLoS One paper on local assembly from short reads by "tagging" DNA via restriction enzymes

Quick one here. Interesting paper from Paul Etter et al. from Eric Johnson's lab at U. Oregon in PLoS ONE: PLoS ONE: Local De Novo Assembly of RAD Paired-End Contigs Using Short Sequencing Reads

Here is the abstract:

"Despite the power of massively parallel sequencing platforms, a drawback is the short length of the sequence reads produced. We demonstrate that short reads can be locally assembled into longer contigs using paired-end sequencing of restriction-site associatedDNA (RAD-PE) fragments. We use this RAD-PE contig approach to identify single nucleotide polymorphisms (SNPs) and determine haplotype structure in threespine stickleback and to sequence E. coli and stickleback genomic DNA with overlapping contigs of several hundred nucleotides. We also demonstrate that adding a circularization step allows the local assembly of contigs up to 5 kilobases (kb) in length. The ease of assembly and accuracy of the individual contigs produced from each RAD site sequence suggests RAD-PE sequencing is a useful way to convert genome-wide short reads into individually-assembled sequences hundreds or thousands of nucleotides long."

Cool paper, & winner of "worst new omics word award": Predatosome

And the bad new omics words keep streaming in. Today's winner of the "Worst New Omics Word Award" is going to Carey Lambert, Chien-Yi Chang, Michael J. Capeness and R. Elizabeth Sockett from Nottingham for their use/ invention of "Predatosome". They use this term in the title of their new PLoS One paper: The First Bite— Profiling the Predatosome in the Bacterial Pathogen Bdellovibrio. Here is the very long sentence where the define it:

The gene products required for the initial invasive predatory processes have not been extensively studied but the genome sequencing of B. bacteriovorus HD100 [1] revealed a genome of 3.85Mb, including a core genome similar to that of non-predatory bacteria and some 40% of the genome comprising a potential predicted “predatosome” of genes, encoding both hydrolytic products that may be employed in prey degradation, and genes that may be required specifically for host predation and thus are not conserved across the Proteobacteria.

The paper is actually quite interesting. They use genomic approaches to characterize a fascinating organism - the bacterial species Bdellovibrio bacteriovorus. This bug is a predatory organism - eating other bacteria. Since it eats them from the inside out, some, including these authors, refer to this organism as a pathogen of other bacteria and their is some discussion here and elsewhere for its potential to serve as a "living antibiotic" in much the same way people are trying to use bacterial viruses (a.k.a. phage).

The paper overall is quite nice on first read. They used microarray studies to characterize gene expression patterns in different phases of the life cycle (see Figure above for the life cycle outline). They backed up this work by quantitative PCR studies and regular RT PCR. And based upon their analysis they found some genes that are "Up-Regulated in Predatory, but Not HI" phase (HI stands for host-independent). And here is where they really tell us what they mean by predatosome:

This category of 240 genes are very interesting as they potentially exclude those genes simply involved with release from attack-phase into growth, namely they should be part of the “predatosome” of predatorily specific genes.

It seems to me this terminology is completely unnecessary. All they need to do is say they are studying the genes related to the predatory phase. To assign these genes to the "predatosome" is a bit much. They continue in the paper to report some really interesting stuff. For example, they also examine another predatory bacterial species, and look at whether there are genes conserved in the process between species. They made some really nice figures by the way about the different phases of hte life cycle in this organism and which genes are expressed:

Anyway - the science in the paper is nice. However, the invention of yet another omics word is a bit much. And thus Lambert et al. are winners of the highly coveted "Worst New Omics Word Award" for their invention of "predatosome". Details on the paper are below - and that is where the figures come from too. (Hat tip to Bora for letting me know about the paper, and the word).

Lambert, C., Chang, C., Capeness, M., & Sockett, R. (2010). The First Bite— Profiling the Predatosome in the Bacterial Pathogen Bdellovibrio PLoS ONE, 5 (1) DOI: 10.1371/journal.pone.0008599

Friendfeed comments below:

#PLoSOne paper keywords revealing: (#Penis #Microbiome #Circumcision #HIV); press release misleading

UPDATE - READ COMMENTS - LEAD AUTHOR HAS GOTTEN PRESS RELEASE CHANGED

A new paper just showed up on PLoS One and it has some serious potential to be important The paper (PLoS ONE: The Effects of Circumcision on the Penis Microbiome) reports on analyses that show differences in the microbiota (which they call the microbiome - basically what bacterial species were present) in men before and after circumcision. And they found some significant differences. It is a nice study of a relatively poorly examined subject - the bacteria found on the penis w/ and w/o circumcision. This is a particularly important topic in light of other studies that have shown that circumcision may provide some protection against HIV infection.

In summary here is what they did - take samples from men before and after circumcision. Isolate DNA. Run PCR amplification reactions to amplify variable regions of rRNA genes from these samples. Then conduct 454 sequencing of these amplified products. And then analyze the sequences to look at the types and #s of different kinds of bacteria.

What they found is basically summarized in their last paragraph

"This study is the first molecular assessment of the bacterial diversity in the male genital mucosa. The observed decrease in anaerobic bacteria after circumcision may be related to the elimination of anoxic microenvironments under the foreskin. Detection of these anaerobic genera in other human infectious and inflammatory pathologies suggests that they may mediate genital mucosal inflammation or co-infections in the uncircumcised state. Hence, the decrease in these anaerobic bacteria after circumcision may complement the loss of the foreskin inner mucosa to reduce the number of activated Langerhans cells near the genital mucosal surface and possibly the risk of HIV acquisition in circumcised men."

And this all sounds interesting and the work seems solid. I note that some friends / colleagues of mine were involved in this including Jacques Ravel who used to be at TIGR and now is at U MD and Paul Kiem who is associated with TGen in Arizona. For anyone interested in HIV, the human microbiome, circumcision, etc, it is probably worth looking at.

However, the press release I just saw from TGen really ticked me off. The title alone did me in "Study suggests why circumcised men are less likely to become infected with HIV". Sure the study did suggest a possible explanation for why circumcised men are less likely to get HIV infections - the paper was justifiably VERY cautious about this inference. They basically state that there are some correlations worth following up.

The press release goes on to say "The study ... could lead to new non-surgical HIV preventative strategies for the estimated 70 percent of men worldwide (more than 2 billion) who, because of religious or cultural beliefs, or logistic or financial barriers, are not likely to become circumcised." Well sure, I guess you could say that. I think they are iplying you could change the microbiome somehow and therefore protect from HIV but that implies (1) that there really is a causal relationship between the microbial differences in HIV protection and (2) that one could change the microbiome easily, which is a big big stretch given how little we know right now.

Anyway - the science seems fine and not over-reaching. But the press release is annoying and misleading. Shocking I know. But this one got to me.

UPDATE - SEE COMMENTS HERE AND IN FRIENDFEED. LEAD AUTHOR GOT PRESS RELEASE CHANGED.



Price, L., Liu, C., Johnson, K., Aziz, M., Lau, M., Bowers, J., Ravel, J., Keim, P., Serwadda, D., Wawer, M., & Gray, R. (2010). The Effects of Circumcision on the Penis Microbiome PLoS ONE, 5 (1) DOI: 10.1371/journal.pone.0008422

PLoS One

Well, PLoS (The Public Library of Science) has announced a new publishing venture called PLoS One.

For those who do not know, PLoS was started a few years ago by a group of scientists (incuding my brother) with the goal of opening up access to scientific literature. For non scientists it may be surprising to find out that scientific and medical research is usually published in journals which are very expensive to purchase. Thus though the research is supposed to be for the benefit of humaninty, it turns out that one of the primary benefits goes to a few companies and societies that publish the journals. Amazingly, even though the journals frequently do little other than repackage papers written by scientists, they not only make enormous amounts of money off of this, they somehow get the copyright to the papers. In general, these journals are a massive roadblock to scientific and medical discovery.

PLoS started a few journals a few years ago to try and provide alternatives to the standard model. These journals are "Open Access" and thus much better for the world. What PLoS has done better than others attempting to make scientific literature open acces is to show that one can publish a very high quality journal that is still free to all (e.g., PLoS Biology).

Now PLoS has announced a completely new way to publish scientific literature. Called PLoS One this seems like a strong attemp to bring scientific publishing into the 21st century. Among the "features" they say will be there are much more rapid publication, publication of all science (with the only criteria being that it is validated by peer review - no restrictions will be made to force the publication to be radically novel) and development of an online community around the publications.

Stay tuned --- we will have to see how it works out but the initial impression I have is that it sounds quite nice.