Here are a few notes about contributing to the Nature Genetics manuscript that I was talking about in a previous post.
note2: I have opened a discussion on Biostar, if you are interested in contributing, look there also.
Scope and purpose of the article
The main purpose of the article is to explain how the results from a GWAS study can be functionally validated. Let’s say that a study has identified a SNP variant that is likely to be associated with a trait: the collaborative article describes the methods that can be used to demonstrate the association, by identifying eQTLs and study them through microarrays to building animal models to simulate the effect of the variant.
In my opinion the key to understand what the manuscript is about, and why it is being written collaboratively, lays in this recent Nature Genetics editorial:
- On beyond GWAS, Nat Gen Editorial 2010
the authors of the Editorial say that most of the times, after a GWAS study has found association between a SNP variant and a risk for a trait, the result is not followed by a functional characterization of the SNP.
(edit) Moreover, you should also look at the home page of the group that has written the original draft, which is the Post Genome Wide Association Study Initiative.
It seems that the same Nature Genetics authors are sponsoring this article as a way to promote discussion about the future after GWAS studies. Instead of proposing to some selected authors to write a review on the topic, they are calling for help from all the scientists interested on Internet. I think it is a nice idea to promote discussion.
Ideas for new paragraphs
I thought of at least two paragraph that could be introduced in the article. I talked about them in the Discussion page of WikiGenes.
The first is to talk about the computational approaches that can be used to predict the function in which a SNP variant is involved. A gene prediction tool can determine whether the variant is within a non-annotated gene or pseudogene. For variants falling in a coding region, there are many approaches to predict the effect on the protein structure or modifications.
The second idea is more related to what I do in my lab, and it is about making use of the information on pathway and gene-gene interactions to improve the results of the study. The goal is that if we are able to understand how selective forces distribute over a pathway of genes, we can make better predictions on how a variant in a certain gene can affect the phenotype if we take into consideration the role of that gene in the pathway. It is kind of a better way to calculate the background distribution, to understand how much variability I should expect from a gene knowing its function. I am writing about this and putting some references in the discussion page and then in the article.