Masking residues using context-specific evolutionary conservation significantly improves short linear motif discovery


Davey, Norman E., Shields, Denis C. and Edwards, Richard J. (2009) Masking residues using context-specific evolutionary conservation significantly improves short linear motif discovery Bioinformatics, 25, (4), pp. 443-450. (doi:10.1093/bioinformatics/btn664).

Download

[img] PDF davey_shields_edwards_2009.pdf - Version of Record
Restricted to Repository staff only

Download (169kB)

Description/Abstract

Motivation:

Short linear motifs (SLiMs) are important mediators of protein–protein interactions. Their short and degenerate nature presents a challenge for computational discovery. We sought to improve SLiM discovery by incorporating evolutionary information, since SLiMs are more conserved than surrounding residues.

Results:

We have developed a new method that assesses the evolutionary signal of a residue in its sequence and structural context. Under-conserved residues are masked out prior to SLiM discovery, allowing incorporation into the existing statistical model employed by SLiMFinder. The method shows considerable robustness in terms of both the conservation score used for individual residues and the size of the sequence neighbourhood.

Optimal parameters significantly improve return of known functional motifs from benchmarking data, raising the return of significant validated SLiMs from typical human interaction datasets from 20% to 60%, while retaining the high level of stringency needed for application to real biological data. The success of this regime indicates that it could be of general benefit to computational annotation and prediction of protein function at the sequence level.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1093/bioinformatics/btn664
ISSNs: 1367-4803 (print)
Related URLs:
Subjects:
Organisations: University of Southampton
ePrint ID: 143455
Date :
Date Event
2009Published
Date Deposited: 12 Apr 2010 09:09
Last Modified: 18 Apr 2017 20:03
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/143455

Actions (login required)

View Item View Item