SLiMPrints paper published

The SLiMPrints paper is now available online at Nucleic Acids Research (doi: 10.1093/nar/gks854; PMID: 22977176).

SLiMPrints: conservation-based discovery of functional motif fingerprints in intrinsically disordered protein regions

Davey NE, Cowan JL, Shields DC, Gibson TJ, Coldwell MJ, Edwards RJ.

Large portions of higher eukaryotic proteomes are intrinsically disordered, and abundant evidence suggests that these unstructured regions of proteins are rich in regulatory interaction interfaces. A major class of disordered interaction interfaces are the compact and degenerate modules known as short linear motifs (SLiMs). As a result of the difficulties associated with the experimental identification and validation of SLiMs, our understanding of these modules is limited, advocating the use of computational methods to focus experimental discovery. This article evaluates the use of evolutionary conservation as a discriminatory technique for motif discovery. A statistical framework is introduced to assess the significance of relatively conserved residues, quantifying the likelihood a residue will have a particular level of conservation given the conservation of the surrounding residues. The framework is expanded to assess the significance of groupings of conserved residues, a metric that forms the basis of SLiMPrints (short linear motif fingerprints), a de novo motif discovery tool. SLiMPrints identifies relatively overconstrained proximal groupings of residues within intrinsically disordered regions, indicative of putatively functional motifs. Finally, the human proteome is analysed to create a set of highly conserved putative motif instances, including a novel site on translation initiation factor eIF2A that may regulate translation through binding of eIF4E.

Server available at bioware.ucd.ie.

CompariMotif V3.6

Both the webserver and SLiMSuite download have now been updated to CompariMotif Version 3.6.

One of the main changes over earlier versions of CompariMotif is that ELM Class exports can now be used directly as input. Any tab-delimited file (*.tdt or *.tsv) with a "Regex" field header will be recognised and motifs extracted using the ELMIdentifier, Regex and Description fields.

To handle some of the more complex motifs now in ELM, the motif splitting function has also been expanded and strengthened. (The caveat is the small bug in the current download which will be fixed in the next release.) In addition to either/or regex elements, variable length non-wildcards are now recognised and will be reformatted for CompariMotif searching.

For example:

Motif [IL]{1,2}[^P].(RG|K)

will be split to form:

Motif_a [IL][^P].RG
Motif_b [IL][^P].K
Motif_c [IL][IL][^P].RG
Motif_d [IL][IL][^P].K

The descriptions will also be appended with "Version 1", "Version 2" etc.

The final minor update replaces ? in motif Regex patterns with .{0,1}. As it uses the same modules for motif input, these changes will also affect SLiMSearch input but not (yet) be taken into consideration for the SLiMChance statistics.

Note. The 2008 version of ELM on the bioware server was manually split and therefore the suffixes added by CompariMotif for later versions of ELM will not necessarily match up.

Minor bug in CompariMotif 3.6 download

The recent fixing up of the server has highlighted a couple of bugs that have crept in during the upgrading of CompariMotif to handle complex motifs better. (More on this in a later post.) The problem is restricted to lower case motifs, so stick to upper case and all will be well. It will be fixed in the next release. A replacement rje_slimlist.py file is available on request if anyone needs to fix it urgently. (This also features replacement of "?" characters with "{0,1}" so these motifs are no longer rejected.)

Bioware servers back up

Following the recent move-induced technical issues, the Bioware webservers are now back on line, with the exception of SLiMSearch 1.0. SLiMSearch2 is also operating with reduced function until another upgrade can be performed in the near future. CompariMotif has been upgraded to Version 3.6 in line with the recent package updates.

A few of the links to help pages etc. might still be broken, so please report anything that is not quite behaving as expected.

New software downloads available

SLiMsuite and SeqSuite downloads have now been updated and are available from my homepage.

The only real change of note since the last release is that CompariMotif can now recognise ELM Class downloads and the motif splitting has been updated to cope with variable-length non-wildcard repeats (e.g. R{0,1}).

The CompariMotif webserver is undergoing some final checks and should be back up shortly, with SLiMFinder and SLiMSearch to follow.

SLiMSuite servers temporarily down

Following some technical issues that have arisen due to some quite major behind-the-scenes re-organisation, the Bioware webserver implementations of SLiMSuite programs have been temporarily taken off-line.

The plan is to give them a bit of attention, iron out any wrinkles that have developed, and then hopefully get them back online over the next week or so. The servers affected are:

• CompariMotif
  
• GOPHER
  
• SLiMDisc (now part of SLiMFinder)
  
• SLiMFinder
  
• SLiMSearch
  
• SLiMSearch 2.0
  

These programs (except SLiMSearch 2.0) are available for download. If you have a particular need for any of these servers, please contact me and I will accelerate its re-appearance.

As each server becomes available, it will be posted here.

Bioware servers behaving erratically

The SLiMSuite servers housed at bioware.ucd.ie are currently behaving a bit strangely. This is under investigation and we hope to have it sorted out soon. If you spot any odd or unexpected behaviour with the servers, please let us know.