Biomedical Computation

MEME ChIP – motif discovery in ChIP-seq datasets

Usage:

meme-chip [options] [-db <motif database>]+ <sequences>

Description

MEME-ChIP performs several motif analysis steps on a set of DNA sequences that you provide. It is especially appropriate for analyzing the bound genomic regions identified in a transcription factor (TF) ChIP-seq experiment.

MEME-ChIP can

  1. discover novel DNA-binding motifs (with MEME and DREME),
  2. determine which motifs are most centrally enriched (with CentriMo),
  3. analyze them for similarity to known binding motifs (with Tomtom), and
  4. automatically group the found motifs by similarity.

It is worth noting that MEME-ChIP is not a motif scanner, but the motifs discovered by it can be used by FIMO or MAST to scan for motif sites.

Input

A set of sequences in FASTA format. Ideally the sequences should be all the same length, between 100 and 500 base-pairs long and centrally enriched for motifs. The immediate regions around individual ChIP-seq “peaks” from a transcription factor (TF) ChIP-seq experiment are ideal. The suggested 100 base-pair minimum size is based on the typical resolution of ChIP-seq peaks but it is useful to have more of the surrounding sequence to give CentriMo the power to tell if a motif is centrally enriched. We recommend that you “repeat mask” your sequences, replacing repeat regions to the “N” character.

Output

MEME ChIP runs each program in its analysis in a different folder in the output directory. A summary file (index.html) is created in the output directory which lists the top motifs found and links to the results for each program.

Options

Option Parameter Description Default Behaviour
General Options
-o name Create a folder called name and write output files in it. This option is not compatible with -oc as only one output folder is allowed. The program behaves as if -oc memechip_out had been specified.
-oc name Create a folder called name but if it already exists allow overwriting the contents. This option is not compatible with -o as only one output folder is allowed. The program behaves as if -oc memechip_out had been specified.
-index-name name Set the file name for the output summary to name. The output summary is named index.html .
-db file Use file containing a database of DNA motifs in MEME format. This database will used by Tomtom and CentriMo. This option may be used multiple times to pass multiple databases. When no databases are provided Tomtom can’t suggest similar motifs and CentriMo is limited to the discovered motifs.
-bfile file Use file specifying background frequencies with programs that support a background (MEME, Tomtom and CentriMo). A background file is calculated from the input sequences and passed to the programs which support it.
-nmeme limit The upper bound on the number of sequences that are passed to MEME. This is required because MEME takes too long to run for very large sequence sets. The number of sequences passed to MEME will be limited to 600.
-ccut size The maximum length of a sequence to use before it is trimmed to a central region of this size. A value of 0 indicates that sequences should not be cut down. A maximum size of 100 is used.
-group-thresh gthr Main threshold for clustering highly similar motifs in MEME-ChIP output. All motifs in a group will have a TOMTOM E-value less than or equal to gthr when compared to the seed motif for the group, which is the most significant motif in the group. A value of 0.05 is used.
-group-weak wthr Secondary threshold for clustering highly similar motifs in MEME-ChIP output. If this is specified by the user, groups will be merged into a more significant group if all their motifs are weakly similar to the seed motif of the more significant group. wthr specifies the TOMTOM E-value threshold for merging groups. Set to be equal to twice the value of the main clustering threshold: 2 * gthr.
-time minutes The maximum time that MEME-ChIP has to run and create output. There is no time limit
-desc description A description of the MEME ChIP run which is displayed in the summary file. No description is displayed in the summary file.
-fdesc file A file containing a description of the MEME ChIP run which will be included in the summary file. The summary file will try to preserve some of the formatting by presenting blocks of text separated by multiple new lines as different paragraphs and replacing single new line characters with line breaks. Only the first 500 characters are used. No description is displayed in the summary file.
-norc Find motifs in given strand only. Find motifs in both strands.
-noecho Don’t echo the commands run. Echo the commands run to standard output.
-help Display a usage message
MEME Specific Options
-meme-mod oops|zoops|anr The number of motif sites that MEME will find per sequence.

oops – One Occurrence Per Sequence,
zoops – Zero or One Occurrence Per Sequence,
anr – Any Number of Repetitions

See -mod in the MEME command-line documentation.

MEME defaults to using zoops mode.
-meme-minw width The minimum motif width that MEME should find. A minimum width of 6 is used unless the maximum width has been set to be less than 6 in which case the maximum width is used.
-meme-maxw width The maximum motif width that MEME should find. A maximum width of 30 is used unless the minimum width has been set to be larger than 30 in which case the minimum width is used.
-meme-nmotifs num The number of motifs that MEME should search for. If 0, MEME will not be run. MEME will find 3 motifs.
-meme-minsites sites The minimum number of sites that MEME needs to find for a motif. MEME doesn’t require any minimum number of sites for a motif.
-meme-maxsites sites The maximum number of sites that MEME will find for a motif. MEME doesn’t limit the number of sites it will find for a motif.
-meme-p np Use parallel version of meme with np processors
-meme-maxsize size Change the largest allowed dataset to be size. Note that the default maximum size exists to warn users that their dataset is possibly too large to process in a reasonable time so please consider carefully before increasing this value. The maximum dataset size is 100000. This should be fine with the default settings for -nmeme and -ccut as the largest possible dataset size would be 60000.
-meme-pal Restrict MEME to searching for palindromes only. MEME searches for any motif not just palindromes.
DREME Specific Options
-dreme-e E-value Stop searching for more motifs if the next best motif found has a worse E-value An E-value threshold of 0.05 is used.
-dreme-m count Stop searching for more motifs if count motifs have been found. If 0, DREME will not be run. There is no limit on the number of motifs.
CentriMo Specific Options
-centrimo-local CentriMo perform local motif enrichment analysis, computing enrichment in every possible sequence region. CentriMo will perform central motif enrichment analysis, computing enrichment in centered regions only.
-centrimo-score score Set the minimum accepted score for a match. A minimum score of 5 is used.
-centrimo-maxreg region Set the size of the maximum region size tested. CentriMo will test all valid region sizes.
-centrimo-ethresh E-value Set the E-value threshold for reporting enriched central regions. An E-value threshold of 10 will be used.
-centrimo-noseq Do not store sequence IDs in the output of CentriMo. CentriMo stores a list of the sequence IDs with matches in the best region for each motif.