# The MEME Suite

## Motif-based sequence analysis tools

## Frequently Asked Questions

- Q. I haven't received my MEME confirmation email?
- Q. Why don't the motif occurrences in the "Summary of Motifs" block diagrams match the occurrences shown in the individual motif block diagrams?
- Q. MAST returns "Your sequence contains unrecognized characters..."
- Q. Is it possible to introduce specific amino acid compositions in the MEME and MAST programs?
- Q. I don't really understand what the pseudocount parameters for tomtom represent, nor how to use them properly.
- Q. MEME Suite won't compile! I get error messages about libxml2 or libxslt. What should I do?

- Q. I haven't received my MEME confirmation email?

  A. You should have received a confirmation email that your job is submitted. If you haven't received this email, then you might have typed in the wrong email address.

  Alternatively, your mail program may be filtering the MEME emails as spam, so check your folders designated as junk e-mail or spam. Try to configure your mail program not to filter out emails from meme@sdsc.edu.

  Please also check with your mail server administrator and see whether your email has been filtered out by spam filters run automatically on all incoming messages by your organization.

- Q. Why don't the motif occurrences in the "Summary of Motifs" block diagrams match the occurrences shown in the individual motif block diagrams?

  A. The motif occurrences shown for a motif in its section of the output are the ones discovered by the MEME algorithm. These occurrences are then used to create a position specific scoring matrix (PSSM) for the motif. The PSSMs for all of the motifs discovered by MEME are then used to search for non-overlapping sets of occurrences of motifs with p-values under 0.0001 using the MAST algorithm. These are displayed in the "Summary of Motifs" block diagram. Individual motif occurrences will sometimes be missing from the "Summary of Motifs" block diagram because of the non-overlapping or minimum p-value requirements. Conversely, there may be motif occurrences in the summary diagram that were not discovered by the MEME algorithm.

- Q. MAST returns "Your sequence contains unrecognized characters..."

  A. The file must be a plain text file. MSWord files, for example, are not acceptable. MSWord files can be converted to plain text by:
  "File"-->"Save As"-->"Save As Type"-->"Plain Text' (*.txt)".

- Q. Is it possible to introduce specific amino acid compositions in the MEME and MAST programs?

  A. MEME can use higher-order background models. However, doing this requires a locally installed MEME and running "fasta-get-markov", which is included in the distribution. The relevant switch to MEME is "-bfile".

  MAST can only use zero-order (compositional) models. This is done automatically on the web server when searching the "upstream" databases using a file based on all upstream regions for the particular organism. As with MEME, users of locally installed MAST can specify their own background files. The switch to MAST is "-bfile".

- Q. I don't really understand what the pseudocount parameters for tomtom represent, nor how to use them properly.

  A. Essentially, a pseudocount corresponds to a Bayesian prior. If you flip a coin 10 times and observe 10 heads in a row, then without a prior, you would estimate the probability of observing a heads on the next round as 100%. But because you have a prior belief that the coin is probably fair, you might pretend that you started off with one heads and one tails. Then you would say that you've seen 1 tails and 11 heads, so your probability of heads would be 91.7%. If you keep flipping the coin all day, and you only ever see heads, then the estimated probability of heads would eventually get very close to 100%.

  The motif pseudocounts work they same way: they allow you to say that, even though we've never seen an "A" in position 3 of the motif, it's still a possibility. Pseudocounts are important for motifs with few known occurrences. If you have a motif built from 100 instances, then the pseudocount is not likely to be important, but if the motif is based on only a handful of instances, then it is.

  Motifs coming out of MEME already have pseudocounts included in them. Otherwise, it's a good idea to add a small pseudocount.

- Q. MEME Suite won't compile! I get error messages about `libxml2` or `libxslt`. What should I do?

  A. `libxml2` is a library for parsing XML files. `libxslt` is a library for processsing XML files. using XSLT stylesheets. MEME Suite will try to use the versions of these libraries already installed on your system. If the libraries can't be found on your system, MEME Suite will build its own copies from source included in the MEME Suite distribution. If MEME Suite detects a local copy of `libxml2`, but no local copy of `libxslt`, it will try to build its own copy of `libxslt`, but it may run into conflicts between the installed versions of `libxml2` and included version of `libxslt` that will keep MEME suite from compiling. If you run into this problem you can force MEME Suite to build both libraries from the included source. Just add the options `--enable-build-libxml2` and `--enable-build-libxslt` to your `configure` command line. For further information about `configure` options see the installation guide.