After tesets of selection on WGS data, there would be a lot of regions as significant in at least one test under the correspongding 0.1% genome-wide FDR. And my question is:
How to prioritize regions for the subsequent research?
1 answer
There are many frameworks to combine the results of multiple tests for positive selection, identifying only those highlighted by more than one method. However this is a complex problem, complicated by the fact that each selection test measures a slightly different type of selection event (e.g. complete or incomplete sweeps, recent or ancient, population-specific sweeps, etc..)
The easiest way is to combine the p-values using Fisher's method. This is not completely correct because the p-values from multiple tests are not always independent, but in general it is accepted. For a discussion, see:
- Peng et al 2010 http://www.nature.com/ejhg/journal/v18/n1/full/ejhg2009115a.html
- Zaykin et al 2008 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569904/
- This biostar discussion How To Combine P-Values Obtained With Different Approaches?
- wikipedia article http://en.wikipedia.org/wiki/Fisher%27s_method
A more sophisticated approach is to use machine learning to combine the tests together. However, this usually requires calculating simulations using different demographic models, in order to have a training and test datasets.
- Grossman 2010, CMS http://www.ncbi.nlm.nih.gov/pubmed/20056855
- Lin et al 2011, Boosting http://www.ncbi.nlm.nih.gov/pubmed/21041556
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It all depends on what kind of research you want to do afterwards...
The mission is to find out genes under selection. But I found there were too many genes significant in at least one test...What do you recommend, such as some experience or papers?