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Blocks analysis is a method of motif finding that restricts motifs to ungapped regions in the alignment. Blocks can be generated from an MSA or they can be extracted from unaligned sequences using a precalculated set of common motifs previously generated from known gene families.<ref name="henikoff1991">{{cite journal | vauthors = Henikoff S, Henikoff JG | title = Automated assembly of protein blocks for database searching | journal = Nucleic Acids Res. | volume = 19 | issue = 23 | pages = 6565–72 | date = December 1991 | pmid = 1754394 | pmc = 329220 | doi = 10.1093/nar/19.23.6565 }}</ref> Block scoring generally relies on the spacing of high-frequency characters rather than on the calculation of an explicit substitution matrix. The [https://web.archive.org/web/20130328131920/http://blocks.fhcrc.org/ BLOCKS] server provides an interactive method to locate such motifs in unaligned sequences.
Statistical pattern-matching has been implemented using both the [[expectation-maximization algorithm]] and the [[Gibbs sampler]]. One of the most common motif-finding tools, known as [[Multiple EM for Motif Elicitation|MEME]], uses expectation maximization and hidden Markov methods to generate motifs that are then used as search tools by its companion MAST in the combined suite [http://meme.sdsc.edu/meme/intro.html MEME/MAST] {{Webarchive|url=https://web.archive.org/web/20100822143504/http://meme.sdsc.edu/meme/intro.html |date=2010-08-22 }}.<ref name="baileyelkan1994">{{cite book |vauthors=Bailey TL, Elkan C |year=1994 |chapter=Fitting a mixture model by expectation maximization to discover motifs in biopolymers |title=Proceedings of the Second International Conference on Intelligent Systems for Molecular Biology |pages=28–36 |publisher=AAAI Press |___location=Menlo Park, California|chapter-url=http://www.cs.toronto.edu/~brudno/csc2417_15/10.1.1.121.7056.pdf}}</ref><ref name="baileygribskov1998">{{cite journal | vauthors = Bailey TL, Gribskov M | title = Combining evidence using p-values: application to sequence homology searches | journal = Bioinformatics | volume = 14 | issue = 1 | pages = 48–54 | date = 1998 | pmid = 9520501 | doi = 10.1093/bioinformatics/14.1.48 | doi-access = free }}</ref>
===Non-coding multiple sequence alignment===
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