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I thought that Needleman-Wunsch is the best approach to align sequences. However, I read that it is impossible to evaluate the statistical significance of the alignment if you do global alignment. So I would like to ask, what is the point of global alignment if we cannot evaluate statistical significance?

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    $\begingroup$ Can you provide more context to this? Statistical significance doesn't normally have anything directly to do with an alignment. Dynamic programming has nothing to do with any of this other than it's a convenient way of implementing things like Needleman-Wunsch. $\endgroup$ – Devon Ryan May 24 at 19:10
  • $\begingroup$ I am sorry. In my notes, it is mentioned that in the case of global alignment you cannot know the statistical significance of the alignment, whereas in the local alignment without gaps you know that the distribution of score is Gumbel and you can calculate p-value, bit score and e-value. And yes when I said dynamic programming, I meant Needleman-Wunsch algorithm. $\endgroup$ – marilu May 24 at 19:25
  • $\begingroup$ Can you say more about how these two things are related? We use dynamic programming in alignment just to speed things up I think. I am not sure whether people are interested in a p-value for global or local alignment. $\endgroup$ – Phoenix Mu May 25 at 2:20
  • $\begingroup$ i mean sequence alignment like in blast. to be sure that the alignment is not by chance $\endgroup$ – marilu May 26 at 16:45
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It's best to flip the question on its head and ask yourself instead, "Do we care about the statistical significance of an individual alignment?" The answer is "yes" if you're in a context like homology modeling, where you're aligning two protein sequences. The answer, however, is a very definite "no" in the context of NGS, where you just want the most likely alignment and a vague assessment of its likelihood of being wrong (for filtering purposes).

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  • $\begingroup$ thank you!but i am interested in homology modeling and not in ngs. So alignment in order to find some relationship between sequences. $\endgroup$ – marilu May 26 at 16:46

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