Abstract
Short linear motifs (SLiMs) are small protein sequence patterns that mediatea large number of critical protein-protein interactions, involved in processes suchas complex formation, signal transduction, localisation and stabilisation. SLiMsshow rapid evolutionary dynamics and are frequently the targets of molecularmimicry by pathogens. Identifying enriched sequence patterns due to convergentevolution in non-homologous proteins has proven to be a successful strategy forcomputational SLiM prediction. Tools of the SLiMSuite package use this strategy,using a statistical model to identify SLiM enrichment based on the evolutionary relationships,amino acid composition and predicted disorder of the input proteins.The quality of input data is critical for successful SLiM prediction. Cytoscape providesa user-friendly, interactive environment to explore interaction networks andselect proteins based on common features, such as shared interaction partners.SLiMScape embeds tools of the SLiMSuite package for de novo SLiM discovery(SLiMFinder and QSLiMFinder) and identifying occurrences/enrichment of knownSLiMs (SLiMProb) within this interactive framework. SLiMScape makes it easier to(1) generate high quality hypothesis-driven datasets for these tools, and (2) visualisepredicted SLiM occurrences within the context of the network.To generate new predictions, users can select nodes from a protein network orprovide a set of Uniprot identifiers. SLiMProb also requires additional query motifinput. Jobs are then run remotely on the SLiMSuite server ( http://rest.slimsuite.unsw.edu.au) for subsequent retrieval and visualisation. SLiMScapecan also be used to retrieve and visualise results from jobs run directly onthe server. SLiMScape and SLiMSuite are open source and freely available viaGitHub under GNU licenses.
Highlights
Many protein-protein interactions (PPIs) are mediated by a short linear motif (SLiM) in one protein interacting with globular domains in another[1]
To take advantage of the recent developments and features of Cytoscape, we have developed SLiMScape 3.x, a redesigned and updated app for Cytoscape 3.x
Implementation and operation SLiMScape calls on the original Python implementations of programs in SLiMSuite; namely SLiMFinder[9], QSLiMFinder[11] and SLiMProb[14]
Summary
Many protein-protein interactions (PPIs) are mediated by a short linear motif (SLiM) in one protein interacting with globular domains in another[1]. SLiMs are short (2–15 amino acids in length) and degenerate (with few residues determining specificity)[4], which makes them hard to identify against a backdrop of highly conserved structural domains These features impart remarkable evolutionary plasticity, and convergent (i.e. independent) evolution of new SLiM occurrences is common[5,6]. Cytoscape is a useful resource for SLiM discovery, enabling visual groupings of proteins that share a common interaction partner and may share a SLiM-mediated mechanism of binding. Such proteins can either be used as input for de novo SLiM discovery approaches[5,6] or explored for enrichment of known motifs[14]. SLiMSuite server jobs can be executed online (http://www.slimsuite.unsw.edu.au/servers.php) and the results imported and visualised using SLiMScape
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