Measure Selective Pressure On Transcription Factor Binding Sites

Question

[Whetting]

Hi,
My transcription factor binds to the consensus ACCN6GGT. However, I have evidence that there are preferred nucleotides within the N6-linker region. I would like to test whether the nucleotide at N1 is under selective pressure. Obviously, this cannot be answered through dN/dS measurements. Does anyone know of any available tools to measure this? I have found several really cool theoretical papers, but no real functional programs yet. The one program i found is evoNC (http://evonc.sourceforge.net/). I would appreciate all suggestions!

Answer 1

[Istvan Albert]

Well that code seems to be about 5 years old - and that does not inspire confidence.

But your problem seems to be fairly simple in that all you need is to characterize the nucleotide distribution at one position relative of the others. You may get by with a much simpler approach. For example get counts for each base or by various ambiguity groups then do a statistical test to see if the counts for the first base differ from the other six.

If they do then you can pursue it further and identify and characterize the differences.

[Whetting]

thanks, I have done the "simple count" approach. It appears to support my hypothesis. What test would you suggest? I am worried about multiple testing?

[Istvan Albert]

well you don't have to worry about multiple testing - just keep track of them and apply the corrections as needed ;-)

Perhaps building a contingency table with the counts and applying something like Fischer Exact test or chi-square test would be a good start.