Choose this mode to look for motifs that are enriched
in the centers of your sequences relative to their flanks.
This mode is appropriate for ChIP-seq and other types of data where you expect
the distribution of motifs to be symmetrical around the sequence centers.
Anywhere
Choose this mode to look for motifs that are enriched in
some confined (local) region along the sequences.
This mode is appropriate when your sequences are all aligned on a genomic
landmark such as transcription start sites or splice junctions and you expect that motifs may be enriched
at specifc locations relative to the genomic landmark.
This mode can also detect centrally enriched motifs, but will have lower statistical power due
to more multiple tests being performed.
Choose this mode if you have just one set of sequences to search for
enriched motifs.
In this mode, CentriMo uses the binomial test
to determine if the number of sequences that have their best
matches to a motif in a given region is greater than expected given
that matches should be uniformly distributed along the sequence.
Absolute and Differential (two datasets)
Choose this mode if you would also like to find motifs that are more
locally enriched in the first set of sequences compared to the second set.
When you choose this mode, you will be able to view the motifs sorted by either
absolute enrichment (E-value) or by differential enrichment (Fisher E-value) via the Sort
menu on CentriMo's report.
CentriMo first determines the regions of localized enrichment in the
primary set of sequences for a given motif as in Absolute mode,
and then it computes the differential enrichment of those regions.
For differential enrichment, CentriMo uses Fisher's exact test
to determine if the number of best matches to the motif in the region
in the primary sequences is surpringly higher than the number of best matches
in the same region of the control sequences.
Using the menu below, select the way you want to input motifs that
will be tested for enrichment in your input sequences.
Use the first menu below to choose how you want to input the motifs, and
the second menu to choose the particular motif database you require.
The background model normalizes for biased distribution of
individual letters in your sequences.
By default CentriMo will create a 0-order Markov sequence model from
the letter frequencies in the primary input sequences.
You may also choose to use a uniform background model or to use
the background model specified by the motifs.
Alternately you may select "Upload background" and input a file containing
a background model.
The downloadable version of the MEME Suite contains a script named
"fasta-get-markov" that you can use to create sequence model files in
the correct format from a FASTA sequence file.
Choose this mode if your sequences are DNA and you want CentriMo
to consider motif matches on either strand to be equivalent.
This mode is usually appropriate for ChIP-seq and similar data.
match given strand only
Choose this mode if your sequences are RNA or if you want to
CentriMo to ignore motif matches on the reverse-complement strand of DNA sequences.
This mode is usually appropriate with CLIP-seq and similar data.
separately
Choose this mode if you want to treat matches on the reverse-complement
strand separately from those on the given strand.
CentriMo will produce separate site distribution plots for each motif
and its reverse-complement.
This mode is is useful when your sequences have strand information,
such as when they are promoter regions.
reflected
Choose this mode if you think the positions of motif matches on the reverse-complement strand should
be reflected around the sequence centers.
This mode is useful with ChIP-seq data for detecting the presence
of (non-palindromic) motifs for co-factors--transcription factors other than the one that was ChIP-ed.
Increase the match score threshold if want CentriMo to ignore
weaker matches to motifs, or decrease it to include them in the analysis.
Sequences with no match to a given motif above the match score threshold are ignored
in computating that motif's enrichment.
Optimize Score
Select option this if you want CentriMo to find the optimal match score threshold.
Independently for each motif, CentriMo will consider all thresholds
above 0 and will choose the one
that maximizes the statistical significance of the motif's enrichment.
This option increases running time and can reduce statistical power
due to increased multiple tests.
Reduce the E-value threshold if you want CentriMo to report
only more significant motif enrichments; increase it to include less significant motif enrichments in the report.
Setting the E-value threshold to the number of motifs in the input database
will cause CentriMo to report a result for every motif.
Note that if there are multiple, overlapping enriched regions, then CentriMo
reports the most significant overlapping region.
Disable this option if you don't want CentriMo to store sequence identifiers
in its output file.
Disabling this option will make the CentriMo output file smaller, but the
CentriMo output will not be able to interactively show you the sizes of the intersection and union
sets of sequences matching the motifs you select.
Click on the menu at the left to see which of the following motif input methods are available.
Type in motifs
When this option is available you may directly input multiple motifs
by typing them (or using "cut-and-paste").
First select the desired motif alphabet using the menu
immediately to the left. If you select the "Custom" option then
you must provide an alphabet definition
in the file input that immediately follows. Warning: custom alphabets are case-sensitive.
You may optionally give each motif an identifier and alternate name by
inputting a line like >Identifer Alternate-Name preceeding the motif.
You can then enter each motif as either matrices, sequence sites or regular expressions.
You can enter multiple motifs by typing an empty line after each motif.
Individual motifs will be shown in square brackets, and errors in your
motifs will be highlighted in red while warnings will be highlighted in
yellow.
Mouse-over individual motifs to display their sequence logos.
View the examples for more information on what is possible.
Upload motifs
When this option is available you may upload a file containing
motifs in MEME motif format. This includes the outputs generated by MEME
and DREME, as well as files you create using the
motif conversion scripts
or manually following the
MEME motif format guidelines.
Databases (select category)
When this option is available you can select the category of
motif database desired from the list below it. Then select the motif
database from the displayed list.
Consult the
motif database documentation
for descriptions of all the motif databases present on this MEME Suite server.
Submitted motifs
This option is only available when you have invoked the current
program by clicking on a button in the output report of a different MEME Suite program.
By selecting this option you will input the motifs sent by that program.
You may input both probability and count matrices of either orientation
and the rules described below will be used to convert the matrix into a
MEME formatted motif.
Alphabet Order
The counts/probabilities are expected to be ordered based on the
alphabetical ordering of their codes. So DNA is ordered ACGT and
protein is ordered ACDEFGHIKLMNPQRSTVWY. For custom alphabets the ordering
goes uppercase letters (A-Z), lowercase letters (a-z), numbers (0-9) and
finally the symbols '*', '-' and '.'.
Matrix Orientation
Matrix motifs may be input with either one position per row (preferred)
which is called row orientation, or one position per column which is
called column orientation. The orientation is determined by picking
which dimension (row or column) is equal to the alphabet size. If both
dimensions are equal to the alphabet size then row orientation is assumed.
If neither dimension is equal to the alphabet size then the closest
that is still smaller than the alphabet size is picked, however if both
are equally smaller then column orientation is assumed. Finally if none of
the above rules work to determine the orientation then row orientation is
assumed.
Site counts
Once the orientation is determined, the sum of the numbers that make up
the first position is calculated and rounded to the nearest integer.
If that value is larger than 1 then the matrix is assumed to be a count
matrix and that value is used as the site count, otherwise the matrix is
assumed to be a probability matrix and a site count of 20 is used.
Converting to a normalized probability matrix
Once the orientation is determined then each number in the matrix is
converted to a normalized probability by dividing by the sum of all the
numbers for that motif position. If any numbers are missing they are
assumed to have the value zero. As a special case if all numbers in a
motif position have the value zero then they are given the uniform
probability of 1 / alphabet size.
Yellow highlighting and red annotations
Red asterisks (*) indicate where the
parser thinks values are missing. A yellow highlighted row or column
with a red number at the end indicates that the counts for that position
don't sum to the same count as the first position. The red number shows
the difference. If the red number is negative then that position sums to
less then the first position, if it is positive then it sums to more than
the first position.
Typed Motifs - Sequence Sites or Regular Expressions
You may input one or more sites of the motif including using ambiguity
codes or bracket expressions to represent multiple possibilities for a
single motif position.
Ambiguity Codes
The DNA and protein alphabets include additional codes that represent
multiple possible bases. For example the DNA alphabet includes W (for weak)
which represents that the given position could be either a A (for adenosine)
or a T (for thymidine).
Bracket Expressions
Bracket expressions also group together multiple codes so they share
a single position. Their syntax is a opening square bracket '[' followed
by one or more codes and a closing square bracket ']'. For example with a
DNA motif the bracket expression [AT] means that both A and T are
acceptable and is equivalent to the ambiguity code W. Any repeats of a
base in a bracket expression are ignored so for example a DNA bracket
expression [AAT] has the same effect as [AT] or [AW] or W.
Multiple sites
When only one site is provided the site count is set to 20, however
you can precisely control the motif by providing multiple sites. Each of
these sites can still contain ambiguity codes and bracket expressions
but a single count will be divided among the selected bases for each
position. When multiple sites are provided the site count will be set
to the number of sites provided.
DNA motifs support the standard 4 codes for the bases: adenosine (A),
cytidine (C), guanosine (G) and thymidine (T) as well as supporting
the following ambiguity codes.
When enabled this field supports selecting motifs from the file with a
space separated list of motif identifiers and/or their positions in the
file.
Any numbers in the range 1 to 999 are assumed to refer to the position
of the selected motif in the file, so the entry "3" always refers to the
third motif. Any other entry is assumed to be a motif identifier.
Motif identifiers can not start with a dash and can only contain
alphanumeric characters as well as colon ':', underscore '_', dot '.'
and dash '-'.
This option can help change the alphabet of motifs from
a base alphabet to a derived alphabet.
This might be useful if you need to compare an extended DNA motif with
a library of DNA motifs, or if you wish to compare RNA motifs to DNA motifs.
Note that this option will also let you do nonsensical things like compare
Protein motifs to DNA motifs so use it with care.
The derived alphabet must have all the core symbols of the alphabet
that it is derived from. For example if the alphabet is derived from DNA
it must have ACGT as core symbols. Expanding the alphabet adds frequencies
of zero for every symbol in the derived alphabet that did not exist in the
base alphabet.
Click on the menu at the left to see which of the following sequence input methods are available.
Type in sequences
When this option is available you may directly input multiple
sequences by typing them. Sequences must be input in
FASTA format.
Upload sequences
When this option is available you may upload a file containing
sequences in FASTA format.
Upload BED file
When this option is available you may upload a file containing
sequence coordinates in BED format.
Databases (select category)
When this option is available you may first select a category of
sequence database from the list below it. Two additional menus will then appear
where you can select the particular database and version desired, respectively.
The full list of available sequence databases and their descriptions
can be viewed HERE.
Submitted sequences
This option is only available when you have invoked the current
program by clicking on a button in the output report of a different MEME Suite program.
By selecting this option you will input the sequences sent by that program.
Specify a file to upload containing
sequence coordinates in BED format.
The file must be based on the exact genome version you specified in the
menus above.
Selecting this option will filter the sequence menu to only contain
databases that have additional information that is specific to a tissue
or cell line.
This option causes MEME Suite to use tissue/cell-specific information
(typically from DNase I or histone modification ChIP-seq data) encoded
as a position specific prior that
has been created by the MEME Suite create-priors
utility. You can see a description of the sequence databases
for which we provide tissue/cell-specific priors
here.
Note that you cannot upload or type in your own sequences
when tissue/cell-specific scanning is selected.
Enter the email address where you want the job notification email to
be sent. Please check that this is a valid email address!
The notification email will include a link to your job results.
Note: You can also access your jobs via the Recent Jobs
menu on the left of all MEME Suite input pages. That menu only
keeps track of jobs submitted during the current session of your internet browser.
Note: Most MEME Suite servers only store results for a couple of days.
So be sure to download any results you wish to keep.
