MEME - Introduction

MEME -- Multiple EM for Motif Elicitation

Motif discovery tool

The input to MEME contains the following fields.

e-mail address
This is the address where the confirmation message and motifs will be sent. Make sure this is a valid e-mail address.
description[optional]
This will be included in the subject lines of the messages MEME will send you. This field is optional so you may leave it blank if you wish.
sequences
This is the group of sequences (the "training set") which you want MEME to analyze for patterns that are shared among the sequences and/or repeat within individual sequences. All of the sequences must be either protein or DNA. You may not mix different types of sequences in the same group. MEME supports a large number of sequence formats. The Web version of MEME requires that the sequences in your group have fewer than characters in total. To specify the sequences you wish MEME to analyze, you can enter either a file name or the actual sequences. Do not enter both.
- file name This should be the name of a file on your computer containing a group of related sequences in an appropriate sequence format.
- actual sequences You may type or cut-and-paste the sequences in an appropriate sequence format in the window provided here.
motif distribution
This is where you tell MEME how you believe occurrences of the motifs are distributed among the sequences. Selecting the correct type of distribution improves the sensitivity and quality of the motif search.
number of motifs
MEME will look for up to this number of distinct motifs in the training set. MEME will stop when this number of motifs has been found, or when none can be found with E-value less than 100.

number of sites[optional]
This is the total number of sites in the training set where a single motif occurs. You can choose different limits for the minimum and maximum number of occurrences that MEME will consider. If you have prior knowledge about the number of occurrences that motifs have in your trainig set, limiting MEME's search in this way can can increase the likelihood of MEME finding true motifs.
For example, if you know that each motif is likely to occur at least 5 times but no more than 8 times in the training set, you could specify:

Minimum

Maximum

MEME will then only report motifs with between 5 and 8 occurrences, inclusive, in the training set. (The same range [5,...,8] will apply, separately, to each motif MEME finds.) MEME may still find motifs with slightly fewer or more occurrences then those you specify. In the above example, if there is a motif in the training set with only 4 occurrences, MEME may still find it, but it will report 5 occurrences, one of which will be erroneous. Likewise, if a motif in the training set has 9 occurrences, MEME will probably still find it, but it will report only 8 of its occurrences.
MEME chooses the number of occurrences to report for each motif by optimizing a statistical heuristic function, restricting the number of occurrences to the range you give here, or using defaults described below if you leave these fields blank.
Note 1:
Leave these fields blank if you have selected "One per sequence" in the "How you think the occurrences... are distributed" field. In that case, each sequence must have exactly one occurrence of each motif. It also doesn't make any sense to set the maximum number of sites to a number larger than the number of sequences if you have chosen the "Zero or one per sequence distribution. In that case, there can never be more occurrences of a motif than there are sequences.
Note 2:
These fields are optional. If you leave them blank, MEME will choose limits depending on the type of occurrence distribution you have specified and the number of sequences (n) in the training set. MEME will also override your settings if they conflict with the type of distribution you have chosen (see Note 1, above).

Default Numbers of Sites for each Motif
type of distribution	minimum sites	maximum sites
one occurrence per sequence	n	n
zero or one occurrence per sequence	sqrt(n)	n
any number of repetitions per sequence	sqrt(n)	min(5*n, 50)

motif width
This is the width (number of characters in the sequence pattern) of a single motif. MEME chooses the optimal width of each motif individually using a statistical heuristic function. You can choose different limits for the minimum and maximum motif widths that MEME will consider. The width of each motif that MEME reports will lie within the limits you choose.
text output format
Choosing this option will cause MEME to produce plain text (ASCII) output. By default, MEME output is in hypertext (HTML) format.
shuffle letters in input sequences
You can ask MEME to shuffle the letters in each of your input sequences. This can be useful for determining if the motifs found by MEME using your (unshuffled) sequences are not statistically significant. To determine this, compare the MAST output you received from MEME for your original sequences with that received using the "Shuffle letters in input sequences" option. (Keep all other MEME parameter settings the same so that the comparison will be valid.) Compare the best p-values for the first motif in the original run to the best p-values for the first motif in the shuffled run. If they are similar (or the p-values in the shuffled run tend to be smaller), then the motif is probably not significant. Repeat this process for each motif bearing in mind that the earlier motifs are most likely to be significant. Concluding that a motif is significant is more problematic. Low p-value occurrences of the motif in many sequences and in a conserved position relative to other motifs (or the ends of the sequence) is evidence that it is statistically significant. You can use the shuffle option to help determine what "low" is for the particular set of sequences and MEME parameters you are using.
search given strand only
MEME searches for motifs on both the given DNA strand and the reverse complement strand by default. Checking this box will cause MEME to search the given DNA strand only.
look for palindromes only
Checking this box causes MEME to search only for DNA palindromes. This causes MEME to average the letter frequencies in corresponding motif columns together. For instance, if the width of the motif is 10, columns 1 and 10, 2 and 9, 3 and 8, etc., are averaged together. The averaging combines the frequency of A in one column with T in the other, and the frequency of C in one column with G in the other. If this box is not checked, the columns are not averaged together.
Clicking on the Start search button causes your sequences to be sent to San Diego Supercomputer Center (SDSC) and analyzed by MEME for repeated patterns.
The results of the MEME analysis are sent to you by e-mail.
No copies of your sequences or analysis results are saved at SDSC after the results have been sent to you.

Discover motifs using MEME
MEME introduction
MEME SYSTEM introduction