MEME System Release Notes
MEME version 3.0 -- December, 2000
- MEME enhancements
- Hypertext output: MEME now reports its output in hypertext (HTML)
format with appropriate internal hot links among the results and the
self-contained documentation on how to interpret them. The
alignments are color-coded by nucleic acid or amino acid category.
- Direct MAST search: MEME motifs can now be used to search
sequence databases using MAST simply by clicking on a button on the
MEME HTML output document in an HTML-capable email reader or browser.
- Direct BLOCKS search: MEME motifs can now be submitted to the
BLOCKS multiple alignment processor by clicking on a button on
the MEME HTML output document in an HTML-capable email reader or
browser. This allows MEME motifs to be converted to LOGOS or trees,
and to be used to search other databases of motifs.
- New objective function: MEME searches for motifs that optimize
the statistical significance of the log likelihood ratio of the
occurrences of the motif.
- E-values: MEME computes and reports the statistical significance
of motifs as the E-value of the log likelihood ratio. This provides
an objective measure of how likely the motif is to be biologically
significant.
- E-value stopping criterion: MEME will now stop when a motif
whose E-value is above a user-given threshold is found. This guarantees
that only motifs with a given E-value or better will be present in the
output.
- Handling reverse complement DNA strands: MEME now handles
reverse complement DNA strands correctly with all model types:
OOPS, ZOOPS and TCM.
- Handling of ambiguous characters: MEME now handles ambiguous
DNA and protein letters by converting them to the character "X".
MEME treats the "X" character as "unknown", and correctly computes
the probabilities of motif occurrences containing it.
- Higher-order background models: MEME now allows the user to
specify a Markov model of arbitrary order via a file of tuple
frequencies. This appears to improve the ability to discriminate
between biologically interesting DNA motifs and motifs that are
artifacts of the higher order statistics of DNA sequence.
- Multiple-alignment-based motif trimming:
MEME defines a motif as
a set of subsequences that can be correctly aligned without gaps.
MEME can now trim
the edges of motifs based on a local multiple alignment with gaps. MEME
first determines the occurrences of the motif, then aligns each
occurrence to the highest-scoring occurrence. These are combined
into a multiple alignment, and MEME looks for a set of columns with
no gaps. If a set of gapless columns at least wide is not
found, MEME searches for a set with at most 1, 2, ... etc gaps until
a set is found.
- Prior distribution on the number of occurrences: MEME now
places a prior on the number of occurrences that controls how
strong the bias towards motifs with a given number of sites is.
Using a prior improves the performance of MEME with DNA, where the
megaprior heuristic (used by default with protein sequences),
is not applicable.
- MAST enhancements
- Combining DNA strands: MAST now combines the score of a
site in a DNA sequence with the score of the corresponding site
on the reverse complement strand. (The final score for the site
is the maximum of the two scores.)
- Scoring DNA strands separately: MAST still allows each strand
of a DNA sequence to be treated as a separate sequence at the
user's request.
- Ignoring reverse complement DNA: MAST also allows the user to
score only the given DNA strand, not scoring the reverse complement
strand at all.
- Background model: MAST now allows the user to specify the
background residue frequencies used for computing E-values of scores.
- Composition-adjusted statistics: MAST can now use a different
random model for each target sequence, based on the letter composition
of that sequence. This can greatly reduce erroneous matches due
to biased sequence compostion.
- New databases:
The MAST website includes several new databases including "upstream"
sequences for E. coli, B. subtilis and S. cerevesiae, and many complete
genomes from GenBank.
- MEME and MAST enhancements:
- Both MEME and MAST can be installed under the following operating systems:
- Linux (various manufacturers)
- SunSparc workstations (SunOS and Solaris operating systems)
- Decalpha workstations (OSF/1 operating system)
- Silicon Graphics workstations (IRIX version 5.3 operating system)
- Intel Paragon parallel computers
- Cray T3D parallel computers
MEME version 2.2 -- February 25, 1998
MEME enhancements:
- Sequence weights can be given in the input sequence file.
- The sites composing each motif are output in BLOCKS or FASTA format.
BLOCKS format motifs can be converted to LOGOS, PSSMS and phylogeny trees
using the
Blocks Multiple Alignment Processor.
- A "negative" dataset may be specified causing the motifs to be optimized
to discriminate between the training set family and the negative family.
(This option is only available when you install MEME on your own computer.)
- An advanced version of the MEME data submission form allows
- discovering palindromic DNA motifs,
- discovering motifs occurring on both DNA strands, and
- discovering more than ten motifs.
MAST enhancements:
- DNA sequences (translated in six reading frames) can be searched
using protein motifs.
- Hypertext (HTML) output
including links to the ENTREZ database and
improved motif diagrams are now output.
- Additional searchable databases added to the MAST website.
- The annotation section of output is smaller now since only
regions in sequences where the motifs are present are printed.
- The ambiguous characters "*" and "-" are now permitted in motifs
and sequence databases. They are treated as a single, unknown
character in databases, and replaced by a weighted average of
scores in motifs.
MEME version 2.1 -- March 25, 1997
MAST output now includes measurements of similarities between
all pairs of motifs in the query and a warning if any motifs
are too similar. (Too similar motifs in a query can cause
some p-values and e-values to be underestimated. These motifs
can be removed from the query and MAST re-run to avoid the problem.)
Cray T3E parallel computer now supported for MEME and MAST.
MEME version 2.0 -- October 17, 1996
The output format of MEME has been
improved to aid readability and user-friendliness.
MEME and MAST (Version 2.0) have been compiled and tested on
- SunSparc workstations (SunOS and Solaris operating systems)
- Decalpha workstations (OSF/1 operating system)
- Silicon Graphics workstations (IRIX version 5.3 operating system)
- Intel Paragon parallel computers
- Cray T3D parallel computers
MAST has been completely rewritten to provide more accurate
p-values and to run significantly faster.
A MAST server has been added to the MEME system website.
The MAST server lets you use the motifs found by MEME in your sequences
to search a wide variety of sequence databases including:
- nr (non-redundant protein and nucleotide databases)
- month (new or revised sequences in the last 30 days)
- swissprot (the last major release of the SWISS-PROT protein sequence
database)
- genpept (protein translations from the GenBank feature table)
- dbest (expressed sequence tag database)
- dbsts (sequence tag site database)
Several improvements have been made to the MEME website:
- You can now give the name of a file containing your sequences
instead of having to cut-and-paste the sequences themselves.
- You may ask MEME to favor wide motifs instead of the (default) narrow
motifs; this is especially useful with small sequence sets (fewer than
10 sequences.)
- The on-line documentation of MEME has been expanded and improved.
- MEME now determines the type of your sequences
(PROTEIN or DNA) automatically.
- The MEME server now runs MAST on your sequences to
make it easy for you to see the ordering and spacing of the motifs
MEME discovered.
NOTE and PROBER have been removed from the MEME system since their
functionality is now superseded by MAST.
MEME version 1.4 -- February 29, 1996
Megaprior heuristic added to MEME.
MEME now uses the megaprior heuristic with TCM models and the modified
megaprior heuristic with ZOOPS models (by default). This greatly improves
the sensitivity and selectivity of motifs using these types of models.
P-value computation added to MAST.
MAST now computes p-values for sequences when searching large databases.
This provides better discrimination between true and false positives than
using z-scores. MAST is still only available via ftp, not via the web
server.
Various bug fixes to MEME.
MEME version 1.3 -- December 18, 1995
MEME web server introduced!
Various bug fixes to MEME.
MEME version 1.2 -- November 27, 1995
MAST homology searcher introduced!
MAST allows accurate homology searches of databases using motifs generated
by MEME. The scores from all motifs characterizing a family are combined,
normalized for sequence length, and sorted by z-score. The output of MAST
is similar to that of BLAST, but, used in conjunction with MEME, MAST
allows searching for sequences related to an entire family, not just a
single sequence in the family. This provides better sensitivity and
selectivity than single-sequence homology searches.
MAST is currently only available in the ftp-able code, not via the web server.
Various bug fixes to MEME.
MEME version 1.1 -- June 30, 1995
Initial release of MEME, NOTE and PROBER.