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A Replica Exchange Monte Carlo Algorithm for Protein Folding in the HP Model

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2007
Abstract: 

Background: The ab initio protein folding problem consists of predicting protein tertiary structurefrom a given amino acid sequence by minimizing an energy function; it is one of the most importantand challenging problems in biochemistry, molecular biology and biophysics. The ab initio proteinfolding problem is computationally challenging and has been shown to be -hard even whenconformations are restricted to a lattice. In this work, we implement and evaluate the replicaexchange Monte Carlo (REMC) method, which has already been applied very successfully to morecomplex protein models and other optimization problems with complex energy landscapes, incombination with the highly effective pull move neighbourhood in two widely studied HydrophobicPolar (HP) lattice models.Results: We demonstrate that REMC is highly effective for solving instances of the square (2D)and cubic (3D) HP protein folding problem. When using the pull move neighbourhood, REMCoutperforms current state-of-the-art algorithms for most benchmark instances. Additionally, weshow that this new algorithm provides a larger ensemble of ground-state structures than theexisting state-of-the-art methods. Furthermore, it scales well with sequence length, and it findssignificantly better conformations on long biological sequences and sequences with a provablyunique ground-state structure, which is believed to be a characteristic of real proteins. We alsopresent evidence that our REMC algorithm can fold sequences which exhibit significant interactionbetween termini in the hydrophobic core relatively easily.Conclusion: We demonstrate that REMC utilizing the pull move neighbourhood significantlyoutperforms current state-of-the-art methods for protein structure prediction in the HP model on2D and 3D lattices. This is particularly noteworthy, since so far, the state-of-the-art methods for2D and 3D HP protein folding – in particular, the pruned-enriched Rosenbluth method (PERM) and,to some extent, Ant Colony Optimisation (ACO) – were based on chain growth mechanisms. Tothe best of our knowledge, this is the first application of REMC to HP protein folding on the cubiclattice, and the first extension of the pull move neighbourhood to a 3D lattice.

Document type: 
Article

Trombone Synthesis by Model and Measurement

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2011
Abstract: 

A physics-based synthesis model of a trombone is developed using filter elements that are both theoretically-based and estimatedfrom measurement. The model consists of two trombone instrument transfer functions: one at the position of the mouthpieceenabling coupling to a lip-valve model and one at the outside of the bell for sound production. The focus of this work is onextending a previously presented measurement technique used to obtain acoustic characterizations of waveguide elements forcylindrical and conical elements, with further development allowing for the estimation of the flared trombone bell reflection andtransmission functions for which no one-parameter traveling wave solution exists. A one-dimensional bell model is developedproviding an approximate theoretical expectation to which estimation results may be compared. Dynamic trombone modelelements, such as those dependent on the bore length, are theoretically and parametrically modeled. As a result, the trombonemodel focuses on accuracy, interactivity, and efficiency, making it suitable for a number of real-time computer music applications.

Document type: 
Article

Generating Test Cases for Marine Safety and Security Scenarios: A Composition Framework

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2012
Abstract: 

In this paper we address the problem of testing complex computer models forinfrastructure protection and emergency response based on detailed and realisticapplication scenarios using advanced computational methods and tools. Specifically,we focus here on testing situation analysis decision support models for marine safety& security operations as a sample application domain. Arguably, methodicalapproaches for analyzing and validating situation analysis methods, decision supportmodels, and information fusion algorithms require realistic vignettes that describe ingreat detail how a situation unfolds over time depending on initial configurations,dynamic environmental conditions and uncertain operational aspects. Meaningfulresults from simulation runs require appropriate test cases, the production of whichis in itself a complex activity. To simplify this task, we introduce here the conceptualdesign of a Vignette Generator that has been developed and tested in an industrialresearch project. We also propose a framework for composing vignettes fromreusable vignette elements together with a formal representation for vignettes usingthe Abstract State Machine method and illustrate the approach by means of variouspractical examples.

Document type: 
Article

A Web-Based Graphical User Interface for Evidence-Based Decision Making for Health Care Allocations in Rural Areas

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2008
Abstract: 

Background: The creation of successful health policy and location of resources increasingly relieson evidence-based decision-making. The development of intuitive, accessible tools to analyse,display and disseminate spatial data potentially provides the basis for sound policy and resourceallocation decisions. As health services are rationalized, the development of tools such graphicaluser interfaces (GUIs) is especially valuable at they assist decision makers in allocating resourcessuch that the maximum number of people are served. GIS can used to develop GUIs that enablespatial decision making.Results: We have created a Web-based GUI (wGUI) to assist health policy makers andadministrators in the Canadian province of British Columbia make well-informed decisions aboutthe location and allocation of time-sensitive service capacities in rural regions of the province. Thistool integrates datasets for existing hospitals and services, regional populations and road networksto allow users to ascertain the percentage of population in any given service catchment who areserved by a specific health service, or baskets of linked services. The wGUI allows policy makersto map trauma and obstetric services against rural populations within pre-specified travel distances,illustrating service capacity by region.Conclusion: The wGUI can be used by health policy makers and administrators with little or noformal GIS training to visualize multiple health resource allocation scenarios. The GUI is poised tobecome a critical decision-making tool especially as evidence is increasingly required fordistribution of health services.

Document type: 
Article

Fast Prediction of RNA-RNA Interaction

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2010
Abstract: 

Background: Regulatory antisense RNAs are a class of ncRNAs that regulate gene expression by prohibiting thetranslation of an mRNA by establishing stable interactions with a target sequence. There is great demand forefficient computational methods to predict the specific interaction between an ncRNA and its target mRNA(s).There are a number of algorithms in the literature which can predict a variety of such interactions - unfortunatelyat a very high computational cost. Although some existing target prediction approaches are much faster, they arespecialized for interactions with a single binding site.Methods: In this paper we present a novel algorithm to accurately predict the minimum free energy structure ofRNA-RNA interaction under the most general type of interactions studied in the literature. Moreover, we introducea fast heuristic method to predict the specific (multiple) binding sites of two interacting RNAs.Results: We verify the performance of our algorithms for joint structure and binding site prediction on a set ofknown interacting RNA pairs. Experimental results show our algorithms are highly accurate and outperform allcompetitive approaches.

Document type: 
Article

The Intelligence in Developing Systems for Molecular Biology

Author: 
Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2007
Document type: 
Report

OrthoClusterDB: An Online Platform for Synteny Blocks

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2009
Abstract: 

Background: The recent availability of an expanding collection of genome sequences driven bytechnological advances has facilitated comparative genomics and in particular the identification ofsynteny among multiple genomes. However, the development of effective and easy-to-use methodsfor identifying such conserved gene clusters among multiple genomes–synteny blocks–as well asdatabases, which host synteny blocks from various groups of species (especially eukaryotes) andalso allow users to run synteny-identification programs, lags behind.Descriptions: OrthoClusterDB is a new online platform for the identification and visualization ofsynteny blocks. OrthoClusterDB consists of two key web pages: Run OrthoCluster and View Synteny.The Run OrthoCluster page serves as web front-end to OrthoCluster, a recently developed programfor synteny block detection. Run OrthoCluster offers full control over the functionalities ofOrthoCluster, such as specifying synteny block size, considering order and strandedness of geneswithin synteny blocks, including or excluding nested synteny blocks, handling one-to-manyorthologous relationships, and comparing multiple genomes. In contrast, the View Synteny page givesaccess to perfect and imperfect synteny blocks precomputed for a large number of genomes,without the need for users to retrieve and format input data. Additionally, genes are cross-linkedwith public databases for effective browsing. For both Run OrthoCluster and View Synteny, identifiedsynteny blocks can be browsed at the whole genome, chromosome, and individual gene level.OrthoClusterDB is freely accessible.Conclusion: We have developed an online system for the identification and visualization ofsynteny blocks among multiple genomes. The system is freely available at http://genome.sfu.ca/orthoclusterdb/.

Document type: 
Article

Sparsification of RNA Structure Prediction Including Pseudoknots

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2010
Abstract: 

Background: Although many RNA molecules contain pseudoknots, computational prediction of pseudoknottedRNA structure is still in its infancy due to high running time and space consumption implied by the dynamicprogramming formulations of the problem.Results: In this paper, we introduce sparsification to significantly speedup the dynamic programming approachesfor pseudoknotted RNA structure prediction, which also lower the space requirements. Although sparsification hasbeen applied to a number of RNA-related structure prediction problems in the past few years, we provide the firstapplication of sparsification to pseudoknotted RNA structure prediction specifically and to handling gappedfragments more generally - which has a much more complex recursive structure than other problems to whichsparsification has been applied. We analyse how to sparsify four pseudoknot structure prediction algorithms,among those the most general method available (the Rivas-Eddy algorithm) and the fastest one (Reeder-Giegerichalgorithm). In all algorithms the number of “candidate” substructures to be considered is reduced.Conclusions: Our experimental results on the sparsified Reeder-Giegerich algorithm suggest a linear speedup overthe unsparsified implementation.

Document type: 
Article

Interaction Profile-Based Protein Classification of Death Domain

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2004
Abstract: 

Background: The increasing number of protein sequences and 3D structure obtained fromgenomic initiatives is leading many of us to focus on proteomics, and to dedicate our experimentaland computational efforts on the creation and analysis of information derived from 3D structure.In particular, the high-throughput generation of protein-protein interaction data from a feworganisms makes such an approach very important towards understanding the molecularrecognition that make-up the entire protein-protein interaction network. Since the generation ofsequences, and experimental protein-protein interactions increases faster than the 3D structuredetermination of protein complexes, there is tremendous interest in developing in silico methodsthat generate such structure for prediction and classification purposes. In this study we focused onclassifying protein family members based on their protein-protein interaction distinctiveness.Structure-based classification of protein-protein interfaces has been described initially by Ponstinglet al. [1] and more recently by Valdar et al. [2] and Mintseris et al. [3], from complex structures thathave been solved experimentally. However, little has been done on protein classification based onthe prediction of protein-protein complexes obtained from homology modeling and dockingsimulation.Results: We have developed an in silico classification system entitled HODOCO (Homologymodeling, Docking and Classification Oracle), in which protein Residue Potential InteractionProfiles (RPIPS) are used to summarize protein-protein interaction characteristics. This systemapplied to a dataset of 64 proteins of the death domain superfamily was used to classify eachmember into its proper subfamily. Two classification methods were attempted, heuristic andsupport vector machine learning. Both methods were tested with a 5-fold cross-validation. Theheuristic approach yielded a 61% average accuracy, while the machine learning approach yielded an89% average accuracy.Conclusion: We have confirmed the reliability and potential value of classifying proteins via theirpredicted interactions. Our results are in the same range of accuracy as other studies that classifyprotein-protein interactions from 3D complex structure obtained experimentally. While ourclassification scheme does not take directly into account sequence information our results are inagreement with functional and sequence based classification of death domain family members.

Document type: 
Article