Notes from the Biomass

The post on the interaction paper that I found peculiar due its stress on the "first analysis" received several comments by email and verbally. Several of them were rather disappointed with the paper in general and stressed that the body of interactions used for inferences was very small and that little novelty was described in general. However, I find nothing "wrong" with the paper and if the editors find it interesting, why shouldn't they publish it?

A similar paper by Zhong and Sternberg in Science this Friday might receive the same criticism - much of it has been seen previously in other organisms, there is little novelty in the methodology. The authors integrate transcription data and interaction data from several organisms and provide experimental evidence for their prediction. The approach is not different from strategies employed by in the String database (Disclaimer: done by my former lab) or work from Lee et al. that also appeared in Science and several others. One might want to comment on the lack of references but given the severe restrictions by the journals it is problematic to select the right ones.
Further in defense of it: The work by Zhong and Sternberg might not seem to be novel in the eyes of the pundits but it is probably of considerable interest for the C. elegans community.

Other memes that often go around with papers from your core expertise in prestigious journals: "This work should not be in Nature Genetics" and "I wonder how it got into Science". Maybe I am just getting older but I relax and think that if these works are accepted, my work has a better chance of getting published too. At the end of the day, good work is recognized in your field even if it is not published in Cell. There are just less people jealous people commenting - is that a bad thing?

Or as a collaborator recently put it: You can get away with publishing good work in mediocre journals but not publishing mediocre work. Focus on your work, not the impact factor accrued by other scientists.

[Note to self: Re-read every Friday until you really believe it]

The analysis of the current data on protein-protein interactions described in human by TBK Gandhi et al in the March issue of Nature Genetics delivers a fair overview - solid but yielding little surprises. The authors compare human, yeast, fly and worm networks and verify a few transfers between species experimentally.

What struck me about the manuscript is the abstract which starts with:
We present the first analysis of the human proteome with regard to interactions between proteins.
Did the work by Lehner and Fraser not analyze human interactions - it is even cited? Many other publications analyzed aspects of the human interactome on many levels, e.g. work from text mining. There are works describing first glimpses into organisms that are not readily accessible for high-throughput methods. For instance, a recent computational analysis of Plasmodium falciparum does not claim to analyze the "interactome" but limits itself to prediction of new functions using protein-protein interactions.


Then again, every step to obtain a complete picture of biological data sets is oversold traditionally. The "complete human genome" was published about five times. There were only few experimental approaches to the problem of delivering a one-dimensional sequence. Given the complexity and the plethora of methods, the "complete human interactome" will be published a hundred times.

If you are but moderately involved in research in innate immunity and Toll like receptors, the Science paper by Philip T. Liu et al, led by Robert Modlin entitled Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response will cross your path soon - in a journal club or on a coffee table conversation.

If your are just interested but have not been exposed to the questions of molecular biology in innate immunity, the publication is noteworthy as it reviews (and probably adds to) the challenges and controversies in the field of Toll like receptors (TLR) mediated signalling. TLRs are a *hot* class of molecules involved in recognition of pathogenic stimuli but are poorly understood given the amount of research they have been attracting.

The researchers focus on the known differences in the susceptibility of population groups to infections of Mycobacterium tuberculosis and on a particular group of TLR, the TLR 1 and 2 heterodimer. Tuberculosis was previously described to be influenced - amongst many other factors - by UV exposure which is involved in the production of vitamin D. The levels of skin melanin and consequently skin color limit the levels of UV light that reach lower regions of the skin where the vitamin is produced.

The hypothesis that vitamin D plays a role in the mediation of TLR signaling in the infection with Mycobacterium tuberculosis is experimentally augmented by showing that one of the key molecules, VDR is expressed upon stimulation with TLR-ligands in human monocytes. The differences in TLR between a caucasian and an afro-american group could be removed by adding the compound 25D3, a precursor to vitamin D, which suggests that it is directly involved in the signaling, not providing an overall benefit - the key finding of the study.

Finally, the authors argue that the some of differences in antimicrobial pathways of mice and humans might be explained by the nocturnal life style of the rodents, which relay TLR signals via nitric oxide instead of vitamin D.

Somehow, this sounds like it would be a good idea to spend some time in the sun to fight prevent infections. The work will be discussed in our lab for sure - if I learn some new insights from our experts, I'll comments it here.

[Links of interest to the article in The Scientist]

Three years after the yeast set, a complete set of knockouts of all genes in E. coli K-12 was published in Molecular Systems Biology[s]. Mutants resulting from transposon mutagenesis were available for about half of the genes previously but this study used the popular knockout method by Datsenko and Wanner to target each gene specifically.

The same group reports[s] the sequencing of another closely related K-12 strain - and probably provides the best sequence information we have for genomes currently.

Next on my wishlist: A complete set of double or triple knockout mutants for paralogous gene families in E.coli or yeast.

Experimental Study of Inequality and Unpredictability in an Artificial Cultural Market[s] is the title of a new study by Salganik, Dodds and Watts published in Science today. It is the perfect piece of publishing in our artificial cultural market containing everything to maximize public impact: pop culture, social networks and a bit of high-school math, showing why experts routinely fail to predict anything.

It would be the perfect forward pass to start a long rant on pop star scientists, scale free networks and the Arctic Monkeys if it wasn't a thought through study delivering unexpected results.

Damn.

[Pop-cultural coverage at Telepolis[de] and Seed magazine]

EMBO journal carries a serious survey [f] of how communication between scientists erodes over time due to "decay" of email addresses. Their survey is based on Medline, analyzed over the last ten years.

One in four e-mail addresses becoming invalid within one year of publication is an alarming rate of decay as it has an impact on the ability of scientists to communicate and exchange material.

The analysis includes - amongst typos and organizational problems - the factor that many email addresses are abandoned voluntarily - unhindered communication might be seen as a nuisance also. Recommended (and it's free).

A very comprehensive survey of protein complexes in yeast, performed by Cellzome AG and the EMBL, can now be found on the advanced online publication pages of Nature. It is obviously an important paper to me - I am one of the many contributors to the study - but I am sure one can consider it as a milestone in the research on protein-protein interactions and complexes.

You need to study molecular evolution longer than most of bioinformaticians grasp of it between writing Perl scripts designing XML interfaces before you can comment on progress in the understanding of molecular evolution. However, the forthcoming edition of Molecular Biology and Evolution includes a publication authored by Michael Lynch that has all the features of a landmark. It puts the view forward that evolution of the eukaryotic genome is largely dominated by the small population sizes that permits the creation and fixation of structures such as introns and long intergenic regions.

Or in Lynch's words:

However, by establishing an essentially permanent change in the population-genetic environment permissive to the genome-wide repatterning of gene structure, the eukaryotic condition also promoted a reliable resource from which natural selection could secondarily build novel forms of organismal complexity. Under this hypothesis, arguments based on molecular, cellular, and/or physiological constraints are insufficient to explain the disparities in gene, genomic, and phenotypic complexity between prokaryotes and eukaryotes.

According to Eike Staub, who notified me of the work, it gained much attention when it was presented at last year's conference of European Society for Evolutionary Biology in Krakow.
In addition to the hypothesis, the work builds upon a encompassing overview of the current state of our knowledge of molecular evolution and I can but recommend to take a couple of quiet hours to delve into it if you are interested in molecular evolution. And who isn't?

Usually, I don't read Nature Neuroscience. I've got nothing much to do with neurons.
Usually, I don't have post about pictures that display cuddly animals.
Usually, I don't link to German sites as I assume the majority of my readership prefers to read in the science pidgin that I use for communication on this site.
However, Riesenmaschine, the blog whose consumption will repay all your pain in having learned German, tells us about this fine work on how dopamin levels affect monogamy in praerie voles and I simply can't resist.

The observation that the selector sequences are complementary to the docking site occurred through a combination of staring at the sequences for months and sheer luck.

Nice final words for the methods section of a pure bioinformatics, single author Cell paper on DSCAM, the enigmatic gene that codes for 38,016 potential proteins via alternative splicing.
[Pubmed, Cell]