Mailund on the Internet

I am now responsible for the BiRC webpages. I have the fancy title of Chairman of the Web Committee (the committe is just Christian Storm and Enette), but I prefer Web Fascist myself.

Anyway, we need to update some of the pages because they are a bit outdated (and somewhat messy on unorganised). The trouble is mainly with the publications page, the software page and the research page.

We need to update the publications page because our old publication manager is dead — we don’t really know what is wrong with it, but no one can log in any more — and in any case the university has mandated a global publication manager anyway. So we are changing our publications page to one that extracts the relevant information from the university publication manager. Not as simple a task as it sounds, but we will manage.

The software page just needs to be cleaned up. There is a lot of software there that is no longer maintained, and we want to get rid of that. Otherwise, it is a simple clean up.

The research page is a bit more of a problem.

How do we present our research to the outside world?

Our current research page is just a list of keywords, with little if any information about what we actually do. So we have known for a while that we should change them. We just haven’t been able to agree on how.

We spent an entire day discussing back and forth on our retreat to Mols Bjerge, last summer, but nothing came out of it. With twenty odd people, there are just too many opinions to get any kind of consensus. (Plus, some of the ideas were clearly thought up by people who didn’t expect to implement them themselves — why are people always so ambitions on others’ behalf?)

This is why you need a Web Fascist. Now I am simply going to dictate how the pages should be!

What do I want on the research pages, then?

I want our research pages to give a clear and accurate picture of the research we do at BiRC. I do not think that the current page does that. It is just a list of random keywords that hints at bioinformatics. If I didn’t know about BiRC, and only had that page to go by, I would think that there was something dodgy about the research center.

I want a list of what we really do work on, and I want to put up proof that we work in these areas!

I believe in honesty when it comes to presenting your work. If you pretend to work on more than you actually do, or if you pretend that your research is cooler than it really is, you end up doing more harm than good. Eventually, people will see the truth, and resent your deception. You are better off being honest, and who knows, maybe your work really is interesting and cool in the first place!

So I want an honest description of what we are doing, and I want to back up that we are honest by proof.

So what do I want?

I want to have a list of our main research areas, with a short description of the research we are doing, and I want a list of recent publications to proof that this is something we are actively working on.

What is a research area, and when are we actively working on it?

I don’t want a long list of everything and the kitchen sink. I want a list of the main research areas.

What is a main research area, then? In the email I sent to BiRC when asking for input in deciding this, I had this definition:

That leads me then to what I consider MAJOR and ACTIVE projects, and thus what I think should be listed on the Research page.

To be even considered, I think it should have at least one of “Current funding”, “Software” or “Recent publications”. If it has none of these, it is not a research project — at best it is an area of interest. Nothing has been produced in such a project, so I am sceptical that it even exists as anything more than a dream.

Now, to be a MAJOR project it should be capable of producing at least a couple of papers a year. When you look at Recent publications, you don’t want to see several years between the papers and you don’t want to see that the latest paper is two years old. Projects that produce less than a couple of papers a year should probably belong as part of another MAJOR project.

The funding isn’t so important for the projects here, I think. It is nice to list it when it exists, since it gives a little bit credibility to the project description, but a project shouldn’t be tied to a grant. We are aiming for projects that lasts longer than individual grants, and ideally we want more grants associated to each project. So go ahead and group minor projects under some broad title until you have grouped enough that you can produce several papers!

This quote might also hint at what I consider an active research area.

To be an ACTIVE project, we again look at the recent publications. If a project didn’t produce a paper within the last two years, it is probably no longer active. Unless we expect something to happen soon (getting new funding or getting a paper accepted Any Day Now(tm)) the project probably should be retired from active projects to old projects.

So this is the approach I am taking. Is it reasonable?

In a previous post I mentioned this review of a recent PLoS Genetics paper. I still haven’t read the actual paper, I am ashamed to admit, but we will read it for a journal club at BiRC next week. Anyway, this morning I read another interesting review, again at Genetic Future: Climate genes: positive or balancing selection?

I should probably bring it to our journal club.

The points in this review is that a linear relationship between climate and gene frequency would only be linear if we ignored the history of the human diaspora out of Africa. The time where selection has affected the genes varies a lot from South East Asia, where humans got to early, to South America, where humans got to late.

Would this type of selection actually result in a neat linear trend, like that seen for the RAPTOR gene? Well, it might, if the timing was just right, but it’s by no means a necessary outcome. There are at least three variables in play here, each of which will have some effect on the current frequency of a positively selected allele: the strength of selection, the starting frequency of the allele in that population, and the amount of time the population has existed in its current environment. For positive selection to result in a clean linear correlation between allele frequency and a climate variable, the latter two factors would have to have had a negligible impact, so that most of the variation is determined by selection intensity.

I think that’s pretty unlikely given what we know about human population history: native Americans, for instance, are the descendants of a cold-adapted population living in Siberia that only relatively recently moved down into the warmer climates of central America; selection has not yet had much time to act in these populations. In contrast, humans in Southern Asia have been in their current climate much longer, giving selection more time to do its work. Thus for variants under positive selection, current frequency will be substantially affected by historical contingencies, and the correlation between allele frequency and selective strength will be rough at best.

There’s also a reference to Voight et al. 2007, a paper I reviewed a few weeks back, on signals of selection in humans, based on extended haplotypes around genes under positive selection. Apparently, these signals are missing for the climate genes.

There is an alternative to positive selection, that could also explain the association between climate and gene frequency:

You’ve probably already guessed my hypothesis: at least some of the genes pulled out from this study (and probably the ones with the tightest correlations) have been the targets of balancing selection. Balancing selection could be acting on climate genes in different ways, but in my mind the most likely mechanism is via heterozygote advantage.

…

This model would result in each population reaching a stable allele frequency that is correlated with the local temperature, regardless of its starting frequency and how long the population had been subjected to that particular environment – so long as there has been enough time for the population to reach equilibrium. This scenario is much more likely to result in a linear correlation between allele frequency and climate variables than a simple positive selection model.

Now, what I am wondering is, how strong does the selection have to be for the allele frequency to reach equilibrium in the late arrival populations (say South Americans), and what kind of signals would we look for in the genome to test if balancing, rather than positive, selection is going on?

I really don’t know — I am too new to genetics to even have a clue — but I bet that this is old stuff in the genetics literature. I’ll have to ask around…