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How does DNA sequence motif discovery work?

How can we computationally extract an unknown motif from a set of target sequences? What are the principles behind the major motif discovery algorithms? Which of these should we use, and how do we know we've found a 'real' motif?

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Figure 1: Starting from a single site, expectation maximization algorithms such as MEME4 alternate between assigning sites to a motif (left) and updating the motif model (right).

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D'haeseleer, P. How does DNA sequence motif discovery work?. Nat Biotechnol 24, 959–961 (2006). https://doi.org/10.1038/nbt0806-959

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