release_notes.html

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<HR>
<P>
<B>MEME version 3.0 -- December, 2000 </B>
<P>

<UL>
  <LI> <B>MEME enhancements</B>
  <P>
  <UL>
    <LI><B>Hypertext output:</B> 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.
    <LI><B>Direct MAST search:</B>  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.
    <LI><B>Direct BLOCKS search:</B>  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.
    <LI><B>New objective function:</B>  MEME searches for motifs that optimize
	the statistical significance of the log likelihood ratio of the
	occurrences of the motif.
    <LI><B>E-values:</B>  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.
    <LI><B>E-value stopping criterion:</B>  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.
    <LI><B>Handling reverse complement DNA strands:</B>  MEME now handles
	reverse complement DNA strands correctly with all model types:
	OOPS, ZOOPS and TCM.
    <LI><B>Handling of ambiguous characters:</B>  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.
    <LI><B>Higher-order background models:</B> 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.
    <LI><B>Multiple-alignment-based motif trimming:</B>  
	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 <minw> wide is not
	found, MEME searches for a set with at most 1, 2, ... etc gaps until
	a set is found.
    <LI><B>Prior distribution on the number of occurrences:</B>  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.
  </UL>

  <P>
  <LI><B>MAST enhancements</B>
  <P>
  <UL>
    <LI><B>Combining DNA strands:</B>  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.)
    <LI><B>Scoring DNA strands separately:</B>  MAST still allows each strand
	of a DNA sequence to be treated as a separate sequence at the
	user's request.
    <LI><B>Ignoring reverse complement DNA:</B>  MAST also allows the user to
	score only the given DNA strand, not scoring the reverse complement
	strand at all.
    <LI><B>Background model:</B>  MAST now allows the user to specify the
	background residue frequencies used for computing E-values of scores.
    <LI><B>Composition-adjusted statistics:</B>  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.
    <LI><B>New databases:</B>

	The MAST website includes several new databases including "upstream"
        sequences for E. coli, B. subtilis and S. cerevesiae, and many complete
	genomes from GenBank.
  </UL>

  <P>
  <LI><B>MEME and MAST enhancements</B>
  <P>
  <UL>
    <LI><B>MEME and MAST can be installed under the following operating systems:</B>
    <UL>

      <LI> Mac OS X
      <LI> Linux (various manufacturers)
      <LI> SunSparc workstations (SunOS and Solaris operating systems)
      <LI> Decalpha workstations (OSF/1 operating system)
      <LI> Silicon Graphics workstations (IRIX version 5.3 operating system)
      <LI> Intel Paragon parallel computers
      <LI> Cray T3D parallel computers
      <LI> IBM SP (AIX operating system)
    </UL>

  </UL>

</UL>

<HR> 
<P>
<B>MEME version 2.2 -- February 25, 1998 </B>
<P>
<UL>
  <LI><B>MEME enhancements</B>
  <UL>
    <LI>Sequence weights can be given in the input sequence file.  
    <LI>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 <A HREF="http://blocks.fhcrc.org/blocks/process_blocks.html">

    Blocks Multiple Alignment Processor</A>.
    <LI>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.)
    <LI>An advanced version of the MEME data submission form allows 
    <UL>
      <LI> discovering palindromic DNA motifs,
      <LI> discovering motifs occurring on both DNA strands, and
      <LI> discovering more than ten motifs.
    </UL>
  </UL>
  <LI><B>MAST enhancements</B>

  <UL>
    <LI>DNA sequences (translated in six reading frames) can be searched
	using protein motifs. 
    <LI><A HREF="mast-output-example.html">Hypertext (HTML) output</A>
	including links to the ENTREZ database and
	improved motif diagrams are now output.
    <LI>Additional searchable databases added to the MAST website.
    <LI>The annotation section of output is smaller now since only
      	regions in sequences where the motifs are present are printed.
    <LI>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.
  </UL>
</UL>

<HR>
<P>
<B>MEME version 2.1 -- March 25, 1997 </B>

<P>
<UL>
  <LI><B>Enhancements</B>
  <UL>
    <LI>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.)
    <LI>Cray T3E parallel computer now supported for MEME and MAST.
  </UL>
</UL>

<HR> 
<P>
<B>MEME version 2.0 -- October 17, 1996 </B>

<P>
<UL>
  <LI><B>Enhancements</B>
  <UL>
    <LI> The output format of MEME has been 
         improved to aid readability and user-friendliness.
    <LI> MEME and MAST  have been compiled and tested on:
    <UL>
      <LI> SunSparc workstations (SunOS and Solaris operating systems)
      <LI> Decalpha workstations (OSF/1 operating system)
      <LI> Silicon Graphics workstations (IRIX version 5.3 operating system)
      <LI> Intel Paragon parallel computers
      <LI> Cray T3D parallel computers 
    </UL>

    <LI>MAST has been completely rewritten to provide more accurate 
        p-values and to run significantly faster.
    <LI>A MAST server has been added to the MEME system website.
    <LI>The MAST server lets you use the motifs found by MEME in your sequences
        to search a wide variety of sequence databases including:
    <UL>
      <LI> nr (non-redundant protein and nucleotide databases)
      <LI> month (new or revised sequences in the last 30 days)
      <LI> swissprot (the last major release of the SWISS-PROT protein sequence 
           database)
      <LI> genpept (protein translations from the GenBank feature table)
      <LI> dbest (expressed sequence tag database)
      <LI> dbsts (sequence tag site database)
    </UL>

    <LI> Several improvements have been made to the MEME website: 
    <UL>
      <LI> You can now give the name of a file containing your sequences 
           instead of having to cut-and-paste the sequences themselves.
      <LI> 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.)
      <LI> The on-line documentation of MEME has been expanded and improved.
      <LI> MEME now determines the type of your sequences
           (PROTEIN or DNA) automatically.
      <LI>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.
    </UL>
    <LI>NOTE and PROBER have been removed from the MEME system since their 
	functionality is now superseded by MAST.
  </UL>

</UL>

<HR>
<P>
<B>MEME version 1.4 -- February 29, 1996 </B>
<P>
<UL>
  <LI>Megaprior heuristic added to MEME.
  <UL>
    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.
  </UL>
  <LI>P-value computation added to MAST.
  <UL> 
    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.
  </UL>

  <LI> Various bug fixes to MEME. 
</UL>

<HR>
<P>
<B>MEME version 1.3 -- December 18, 1995 </B>
<P>
<UL>
  <LI>MEME web server introduced!
  <LI> Various bug fixes to MEME. 
</UL>

<HR>
<P>
<B>MEME version 1.2 -- November 27, 1995 </B>
<P>
<UL>
  <LI> MAST homology searcher introduced!
  <UL>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.
  </UL>
  <LI> Various bug fixes to MEME.
</UL>

<HR> 

<P>
<B>MEME version 1.1 -- June 30, 1995 </B>
<P>
<UL>
  <LI> Initial release of MEME, NOTE and PROBER.
</UL>

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