DoReMi: context-based prioritization of linear motif matches.

Many protein domains bind to short peptide sequences, called linear motifs. Data on their sequence specificities is sparse, which is why biologists usually resort to basic pattern searches to identify new putative binding sites for experimental follow-up. Most motifs have poor specificity and prioritization of the matches is thus crucial when scanning a full proteome with a pattern.

SLiMScape: a protein short linear motif analysis plugin for Cytoscape.

Background: Computational protein short linear motif discovery can use protein interaction information to search for motifs among proteins which share a common interactor. Cytoscape provides a visual interface for protein networks but there is no streamlined way to rapidly visualize motifs in a network of proteins, or to integrate computational discovery with such visualizations.

Results: We present SLiMScape, a Cytoscape plugin, which enables both de novo motif discovery and searches for instances of known motifs.

PeptideLocator: prediction of bioactive peptides in protein sequences.

Motivation: Peptides play important roles in signalling, regulation and immunity within an organism. Many have successfully been used as therapeutic products often mimicking naturally occurring peptides. Here we present PeptideLocator for the automated prediction of functional peptides in a protein sequence.

Towards the improved discovery and design of functional peptides: common features of diverse classes permit generalized prediction of bioactivity.

The conventional wisdom is that certain classes of bioactive peptides have specific structural features that endow their particular functions. Accordingly, predictions of bioactivity have focused on particular subgroups, such as antimicrobial peptides. We hypothesized that bioactive peptides may share more general features, and assessed this by contrasting the predictive power of existing antimicrobial predictors as well as a novel general predictor, PeptideRanker, across different classes of peptides.

Peptide-binding domains: are limp handshakes safest?

Interactions between short peptides within proteins and peptide-binding domains can trigger many important cell signaling processes, and their interactions are typically of modest affinity. A study showed that this modest affinity appears to be favored by evolution. They used phage display selection to discover "superbinder" Src Homology 2 (SH2) domains, which bound peptides with much stronger affinity than naturally occurring SH2 domains.

Profile-based short linear protein motif discovery.

Background: Short linear protein motifs are attracting increasing attention as functionally independent sites, typically 3-10 amino acids in length that are enriched in disordered regions of proteins. Multiple methods have recently been proposed to discover over-represented motifs within a set of proteins based on simple regular expressions. Here, we extend these approaches to profile-based methods, which provide a richer motif representation.

ELM--the database of eukaryotic linear motifs.

Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization.

Prediction of short linear protein binding regions.

Short linear motifs in proteins (typically 3-12 residues in length) play key roles in protein-protein interactions by frequently binding specifically to peptide binding domains within interacting proteins. Their tendency to be found in disordered segments of proteins has meant that they have often been overlooked. Here we present SLiMPred (short linear motif predictor), the first general de novo method designed to computationally predict such regions in protein primary sequences independent of experimentally defined homologs and interactors.

SLiMSearch 2.0: biological context for short linear motifs in proteins.

Short, linear motifs (SLiMs) play a critical role in many biological processes. The SLiMSearch 2.0 (Short, Linear Motif Search) web server allows researchers to identify occurrences of a user-defined SLiM in a proteome, using conservation and protein disorder context statistics to rank occurrences.

SLiMFinder: a web server to find novel, significantly over-represented, short protein motifs.

Short, linear motifs (SLiMs) play a critical role in many biological processes, particularly in protein-protein interactions. The Short, Linear Motif Finder (SLiMFinder) web server is a de novo motif discovery tool that identifies statistically over-represented motifs in a set of protein sequences, accounting for the evolutionary relationships between them. Motifs are returned with an intuitive P-value that greatly reduces the problem of false positives and is accessible to biologists of all disciplines.

EpiC: an open resource for exploring epitopes to aid antibody-based experiments.

Antibodies are a primary research tool for a diverse range of experiments in biology, from development to pathology. Their utility is derived from their ability to specifically identify proteins at a high level of sensitivity. This diversity of experimental requirements stretches the capabilities of these key research reagents.

ELM: the status of the 2010 eukaryotic linear motif resource.

Linear motifs are short segments of multidomain proteins that provide regulatory functions independently of protein tertiary structure. Much of intracellular signalling passes through protein modifications at linear motifs. Many thousands of linear motif instances, most notably phosphorylation sites, have now been reported.

A community standard format for the representation of protein affinity reagents.

Protein affinity reagents (PARs), most commonly antibodies, are essential reagents for protein characterization in basic research, biotechnology, and diagnostics as well as the fastest growing class of therapeutics. Large numbers of PARs are available commercially; however, their quality is often uncertain. In addition, currently available PARs cover only a fraction of the human proteome, and their cost is prohibitive for proteome scale applications.

Thermal equivalence of DNA duplexes for probe design.

We present the theory of thermal equivalence in the framework of the Peyrard-Bishop model and some of its anharmonic variants. The thermal equivalence gives rise to a melting index τ which maps closely the experimental DNA melting temperatures for short DNA sequences. We show that the efficient calculation of the melting index can be used to analyse the parameters of the Peyrard-Bishop model and propose an improved set of Morse potential parameters.

Optimal probe length varies for targets with high sequence variation: implications for probe library design for resequencing highly variable genes.

Background: Sequencing by hybridisation is an effective method for obtaining large amounts of DNA sequence information at low cost. The efficiency of SBH depends on the design of the probe library to provide the maximum information for minimum cost. Long probes provide a higher probability of non-repeated sequences but lead to an increase in the number of probes required whereas short probes may not provide unique sequence information due to repeated sequences.

Understanding eukaryotic linear motifs and their role in cell signaling and regulation.

It is now clear that a detailed picture of cell regulation requires a comprehensive understanding of the abundant short protein motifs through which signaling is channeled. The current body of knowledge has slowly accumulated through piecemeal experimental investigation of individual motifs in signaling. Computational methods contributed little to this process.

An analysis of the feasibility of short read sequencing.

Several methods for ultra high-throughput DNA sequencing are currently under investigation. Many of these methods yield very short blocks of sequence information (reads). Here we report on an analysis showing the level of genome sequencing possible as a function of read length.