ORCID Profile
0000-0002-5065-4980
Current Organisation
Dalhousie University
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Publisher: Public Library of Science (PLoS)
Date: 20-02-2009
Publisher: Oxford University Press (OUP)
Date: 22-02-2005
DOI: 10.1093/BIOINFORMATICS/BTI335
Abstract: Multiple sequence alignment at the level of whole proteomes requires a high degree of automation, precluding the use of traditional validation methods such as manual curation. Since evolutionary models are too general to describe the history of each residue in a protein family, there is no single algorithm/model combination that can yield a biologically or evolutionarily optimal alignment. We propose a 'shotgun' strategy where many different algorithms are used to align the same family, and the best of these alignments is then chosen with a reliable objective function. We present WOOF, a novel 'word-oriented' objective function that relies on the identification and scoring of conserved amino acid patterns (words) between pairs of sequences. Tests on a subset of reference protein alignments from BAliBASE showed that WOOF tended to rank the (manually curated) reference alignment highest among 1060 alternative (automatically generated) alignments for a majority of protein families. Among the automated alignments, there was a strong positive relationship between the WOOF score and similarity to the reference alignment. The speed of WOOF and its independence from explicit considerations of three-dimensional structure make it an excellent tool for analyzing large numbers of protein families. On request from the authors.
Publisher: Oxford University Press (OUP)
Date: 29-10-2019
DOI: 10.1093/NAR/GKZ935
Abstract: The Comprehensive Antibiotic Resistance Database (CARD card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models and bioinformatics tools on the molecular basis of bacterial antimicrobial resistance (AMR). CARD focuses on providing high-quality reference data and molecular sequences within a controlled vocabulary, the Antibiotic Resistance Ontology (ARO), designed by the CARD biocuration team to integrate with software development efforts for resistome analysis and prediction, such as CARD’s Resistance Gene Identifier (RGI) software. Since 2017, CARD has expanded through extensive curation of reference sequences, revision of the ontological structure, curation of over 500 new AMR detection models, development of a new classification paradigm and expansion of analytical tools. Most notably, a new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes. By adding these resistance variants to CARD, we are able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants. Here, we describe updates and recent expansions to CARD and its biocuration process, including new resources for community biocuration of AMR molecular reference data.
Publisher: AIP
Date: 2008
DOI: 10.1063/1.2883829
Publisher: Cold Spring Harbor Laboratory
Date: 27-07-2009
Abstract: The increasing availability of genetic sequence data associated with explicit geographic and ecological information is offering new opportunities to study the processes that shape bio ersity. The generation and testing of hypotheses using these data sets requires effective tools for mathematical and visual analysis that can integrate digital maps, ecological data, and large genetic, genomic, or metagenomic data sets. GenGIS is a free and open-source software package that supports the integration of digital map data with genetic sequences and environmental information from multiple s le sites. Essential bioinformatic and statistical tools are integrated into the software, allowing the user a wide range of analysis options for their sequence data. Data visualizations are combined with the cartographic display to yield a clear view of the relationship between geography and genomic ersity, with a particular focus on the hierarchical clustering of sites based on their similarity or phylogenetic proximity. Here we outline the features of GenGIS and demonstrate its application to georeferenced microbial metagenomic, HIV-1, and human mitochondrial DNA data sets.
Publisher: Springer New York
Date: 29-11-2016
DOI: 10.1007/978-1-4939-6622-6_16
Abstract: Lateral genetic transfer (LGT) is the process by which genetic material moves between organisms (and viruses) in the biosphere. Among the many approaches developed for the inference of LGT events from DNA sequence data, methods based on the comparison of phylogenetic trees remain the gold standard for many types of problem. Identifying LGT events from sequenced genomes typically involves a series of steps in which homologous sequences are identified and aligned, phylogenetic trees are inferred, and their topologies are compared to identify unexpected or conflicting relationships. These types of approach have been used to elucidate the nature and extent of LGT and its physiological and ecological consequences throughout the Tree of Life. Advances in DNA sequencing technology have led to enormous increases in the number of sequenced genomes, including ultra-deep s ling of specific taxonomic groups and single cell-based sequencing of unculturable "microbial dark matter." Environmental shotgun sequencing enables the study of LGT among organisms that share the same habitat.This abundance of genomic data offers new opportunities for scientific discovery, but poses two key problems. As ever more genomes are generated, the assembly and annotation of each in idual genome receives less scrutiny and with so many genomes available it is tempting to include them all in a single analysis, but thousands of genomes and millions of genes can overwhelm key algorithms in the analysis pipeline. Identifying LGT events of interest therefore depends on choosing the right dataset, and on algorithms that appropriately balance speed and accuracy given the size and composition of the chosen set of genomes.
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.TIM.2005.11.004
Abstract: Non-tree-based ("surrogate") methods have been used to identify instances of lateral genetic transfer in microbial genomes but agreement among predictions of different methods can be poor. It has been proposed that this disagreement arises because different surrogate methods are biased towards the detection of certain types of transfer events. This conjecture is supported by a rigorous phylogenetic analysis of 3776 proteins in Escherichia coli K12 MG1655 to map the ages of transfer events relative to one another.
Publisher: Springer Science and Business Media LLC
Date: 09-08-2011
Abstract: The assignment of taxonomic attributions to DNA fragments recovered directly from the environment is a vital step in metagenomic data analysis. Assignments can be made using rank-specific classifiers, which assign reads to taxonomic labels from a predetermined level such as named species or strain, or rank-flexible classifiers, which choose an appropriate taxonomic rank for each sequence in a data set. The choice of rank typically depends on the optimal model for a given sequence and on the breadth of taxonomic groups seen in a set of close-to-optimal models. Homology-based ( e.g ., LCA) and composition-based ( e.g ., PhyloPythia, TACOA) rank-flexible classifiers have been proposed, but there is at present no hybrid approach that utilizes both homology and composition. We first develop a hybrid, rank-specific classifier based on BLAST and Naïve Bayes (NB) that has comparable accuracy and a faster running time than the current best approach, PhymmBL. By substituting LCA for BLAST or allowing the inclusion of suboptimal NB models, we obtain a rank-flexible classifier. This hybrid classifier outperforms established rank-flexible approaches on simulated metagenomic fragments of length 200 bp to 1000 bp and is able to assign taxonomic attributions to a subset of sequences with few misclassifications. We then demonstrate the performance of different classifiers on an enhanced biological phosphorous removal metagenome, illustrating the advantages of rank-flexible classifiers when representative genomes are absent from the set of reference genomes. Application to a glacier ice metagenome demonstrates that similar taxonomic profiles are obtained across a set of classifiers which are increasingly conservative in their classification. Our NB-based classification scheme is faster than the current best composition-based algorithm, Phymm, while providing equally accurate predictions. The rank-flexible variant of NB, which we term ε-NB, is complementary to LCA and can be combined with it to yield conservative prediction sets of very high confidence. The simple parameterization of LCA and ε-NB allows for tuning of the balance between more predictions and increased precision, allowing the user to account for the sensitivity of downstream analyses to misclassified or unclassified sequences.
Publisher: Springer Science and Business Media LLC
Date: 18-09-2006
Abstract: Genetic recombination can produce heterogeneous phylogenetic histories within a set of homologous genes. These recombination events can be obscured by subsequent residue substitutions, which consequently complicate their detection. While there are many algorithms for the identification of recombination events, little is known about the effects of subsequent substitutions on the accuracy of available recombination-detection approaches. We assessed the effect of subsequent substitutions on the detection of simulated recombination events within sets of four nucleotide sequences under a homogeneous evolutionary model. The amount of subsequent substitutions per site, prior evolutionary history of the sequences, and reciprocality or non-reciprocality of the recombination event all affected the accuracy of the recombination-detecting programs examined. Bayesian phylogenetic-based approaches showed high accuracy in detecting evidence of recombination event and in identifying recombination breakpoints. These approaches were less sensitive to parameter settings than other methods we tested, making them easier to apply to various data sets in a consistent manner. Post-recombination substitutions tend to diminish the predictive accuracy of recombination-detecting programs. The best method for detecting recombined regions is not necessarily the most accurate in identifying recombination breakpoints. For difficult detection problems involving highly ergent sequences or large data sets, different types of approach can be run in succession to increase efficiency, and can potentially yield better predictive accuracy than any single method used in isolation.
Publisher: Springer Science and Business Media LLC
Date: 02-08-2012
Publisher: Proceedings of the National Academy of Sciences
Date: 21-09-2005
Abstract: The extent to which lateral genetic transfer has shaped microbial genomes has major implications for the emergence of community structures. We have performed a rigorous phylogenetic analysis of ,000 proteins from genomes of 144 prokaryotes to determine the contribution of gene sharing to current prokaryotic ersity, and to identify “highways” of sharing between lineages. The inferred relationships suggest a pattern of inheritance that is largely vertical, but with notable exceptions among closely related taxa, and among distantly related organisms that live in similar environments.
Publisher: Oxford University Press (OUP)
Date: 04-02-2009
DOI: 10.1093/BIOINFORMATICS/BTP044
Abstract: Summary: A phenotypic character has a convex mapping to a given phylogenetic tree if each character state can be assigned a single point of origin in the tree. However, phenomena such as convergent evolution and lateral genetic transfer can lead to intermingling of character states and a consequent non-convex mapping. The phylogenetic heterogeneity of different characters can identify subsets of states that are non-randomly associated or which may have been transferred from one lineage to another. We have developed Radié, an interactive 3D Java application for mapping character states to the leaves and internal edges of a radial phylogenetic tree. In Radié each state of a given character is associated with a unique color, and internal edges with many descendant character states can be represented in a number of different ways to illustrate the ersity within each group. Availability: Radié is freely available for download at kiwi.cs.dal.ca/~beiko/software-and-data/radie source code is available upon request from the authors. Contact: beiko@cs.dal.ca Supplementary information: Supplementary data are available at Bioinformatics online.
Publisher: IEEE
Date: 08-2009
Publisher: Springer Science and Business Media LLC
Date: 2003
DOI: 10.1038/421217A
Publisher: American Society for Microbiology
Date: 15-04-2002
DOI: 10.1128/JB.184.8.2072-2080.2002
Abstract: Darwin's paradigm holds that the ersity of present-day organisms has arisen via a process of genetic descent with modification, as on a bifurcating tree. Evidence is accumulating that genes are sometimes transferred not along lineages but rather across lineages. To the extent that this is so, Darwin's paradigm can apply only imperfectly to genomes, potentially complicating or perhaps undermining attempts to reconstruct historical relationships among genomes (i.e., a genome tree). Whether most genes in a genome have arisen via treelike (vertical) descent or by lateral transfer across lineages can be tested if enough complete genome sequences are used. We define a phylogenetically discordant sequence (PDS) as an open reading frame (ORF) that exhibits patterns of similarity relationships statistically distinguishable from those of most other ORFs in the same genome. PDSs represent between 6.0 and 16.8% (mean, 10.8%) of the analyzable ORFs in the genomes of 28 bacteria, eight archaea, and one eukaryote ( Saccharomyces cerevisiae ). In this study we developed and assessed a distance-based approach, based on mean pairwise sequence similarity, for generating genome trees. Exclusion of PDSs improved bootstrap support for basal nodes but altered few topological features, indicating that there is little systematic bias among PDSs. Many but not all features of the genome tree from which PDSs were excluded are consistent with the 16S rRNA tree.
Publisher: Humana Press
Date: 2009
Publisher: American Society for Microbiology
Date: 08-2011
DOI: 10.1128/JB.01524-10
Abstract: The widespread presence of antibiotic resistance and virulence among Staphylococcus isolates has been attributed in part to lateral genetic transfer (LGT), but little is known about the broader extent of LGT within this genus. Here we report the first systematic study of the modularity of genetic transfer among 13 Staphylococcus genomes covering four distinct named species. Using a topology-based phylogenetic approach, we found, among 1,354 sets of homologous genes examined, strong evidence of LGT in 368 (27.1%) gene sets, and weaker evidence in another 259 (19.1%). Within-gene and whole-gene transfer contribute almost equally to the topological discordance of these gene sets against a reference phylogeny. Comparing genetic transfer in single-copy and in multicopy gene sets, we observed a higher frequency of LGT in the latter, and a substantial functional bias in cases of whole-gene transfer (little such bias was observed in cases of fragmentary genetic transfer). We found evidence that lateral transfer, particularly of entire genes, impacts not only functions related to antibiotic, drug, and heavy-metal resistance, as well as membrane transport, but also core informational and metabolic functions not associated with mobile elements. Although patterns of sequence similarity support the cohesion of recognized species, LGT within S. aureus appears frequently to disrupt clonal complexes. Our results demonstrate that LGT and gene duplication play important parts in functional innovation in staphylococcal genomes.
Publisher: Humana Press
Date: 2008
DOI: 10.1007/978-1-60327-159-2_21
Abstract: Nucleotide sequences of microbial genomes provide evidence that genes have been shared among organisms, a phenomenon known as lateral genetic transfer (LGT). Hypotheses about the importance of LGT in the evolution and ersification of microbes can be tested by analyzing the extensive quantities of sequence data now available. Some analysis methods identify genes with sequence features that differ from those of the surrounding genome, whereas other methods are based on inference and comparison of phylogenetic trees. A large-scale search for LGT in 144 genomes using phylogenetic methods has revealed that although parent-to-offspring ("vertical") inheritance has been the dominant mode of gene transmission, LGT has nonetheless been frequent, especially among organisms that are closely related or share the same habitat. This chapter outlines how bioinformatic and phylogenetic analyses can be built into a workflow to identify LGT among microbial genomes.
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.WATRES.2010.07.028
Abstract: The role of Candidatus "Accumulibacter phosphatis" (Accumulibacter) in enhanced biological phosphorus removal (EBPR) is well established but the relevance of different Accumulibacter clades to the performance of EBPR systems is unknown. We developed a terminal-restriction fragment length polymorphism (T-RFLP) technique to monitor changes in the relative abundance of key members of the bacterial community, including Accumulibacter clades, in four replicate mini-sequencing batch reactors (mSBRs) operated for EBPR over a 35-day period. The ability of the T-RFLP technique to detect trends was confirmed using fluorescence in situ hybridisation (FISH). EBPR performance varied between reactors and over time by day 35, performance was maintained in mSBR2 whilst it had deteriorated in mSBR1. However, reproducible trends in structure-function relationships were detected in the mSBRs. EBPR performance was strongly associated with the relative abundance of total Accumulibacter. A shift in the ratio of the dominant Accumulibacter clades was also detected, with Type IA associated with good EBPR performance and Type IIC associated with poor EBPR performance. Changes in ecosystem function of the mSBRs in the early stages of the experiment were more closely associated with changes in the abundance of (unknown) members of the flanking community than of either Accumulibacter or Candidatus "Competibacter phosphatis". This study therefore reveals a hitherto unrecorded and complex relationship between Accumulibacter clades, the flanking community and ecosystem function of laboratory-scale EBPR systems.
Publisher: Public Library of Science (PLoS)
Date: 24-09-2009
Publisher: Oxford University Press (OUP)
Date: 23-07-2014
DOI: 10.1093/BIOINFORMATICS/BTU494
Abstract: Summary: STAMP is a graphical software package that provides statistical hypothesis tests and exploratory plots for analysing taxonomic and functional profiles. It supports tests for comparing pairs of s les or s les organized into two or more treatment groups. Effect sizes and confidence intervals are provided to allow critical assessment of the biological relevancy of test results. A user-friendly graphical interface permits easy exploration of statistical results and generation of publication-quality plots. Availability and implementation: STAMP is licensed under the GNU GPL. Python source code and binaries are available from our website at: kiwi.cs.dal.ca/Software/STAMP Contact: donovan.parks@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online.
Publisher: Oxford University Press (OUP)
Date: 10-2006
DOI: 10.1086/507537
Abstract: The factors behind the reemergence of severe, invasive group A streptococcal (GAS) diseases are unclear, but it could be caused by altered genetic endowment in these organisms. However, data from previous studies assessing the association between single genetic factors and invasive disease are often conflicting, suggesting that other, as-yet unidentified factors are necessary for the development of this class of disease. In this study, we used a targeted GAS virulence microarray containing 226 GAS genes to determine the virulence gene repertoires of 68 GAS isolates (42 associated with invasive disease and 28 associated with noninvasive disease) collected in a defined geographic location during a contiguous time period. We then employed 3 advanced machine learning methods (genetic algorithm neural network, support vector machines, and classification trees) to identify genes with an increased association with invasive disease. Virulence gene profiles of in idual GAS isolates varied extensively among these geographically and temporally related strains. Using genetic algorithm neural network analysis, we identified 3 genes with a marginal overrepresentation in invasive disease isolates. Significantly, 2 of these genes, ssa and mf4, encoded superantigens but were only present in a restricted set of GAS M-types. The third gene, spa, was found in variable distributions in all M-types in the study. Our comprehensive analysis of GAS virulence profiles provides strong evidence for the incongruent relationships among any of the 226 genes represented on the array and the overall propensity of GAS to cause invasive disease, underscoring the pathogenic complexity of these diseases, as well as the importance of multiple bacteria and/or host factors.
Publisher: Oxford University Press (OUP)
Date: 08-2006
DOI: 10.1080/10635150600812544
Abstract: Markov chain Monte Carlo (MCMC) is a methodology that is gaining widespread use in the phylogenetics community and is central to phylogenetic software packages such as MrBayes. An important issue for users of MCMC methods is how to select appropriate values for adjustable parameters such as the length of the Markov chain or chains, the s ling density, the proposal mechanism, and, if Metropolis-coupled MCMC is being used, the number of heated chains and their temperatures. Although some parameter settings have been examined in detail in the literature, others are frequently chosen with more regard to computational time or personal experience with other data sets. Such choices may lead to inadequate s ling of tree space or an inefficient use of computational resources. We performed a detailed study of convergence and mixing for 70 randomly selected, putatively orthologous protein sets with different sizes and taxonomic compositions. Replicated runs from multiple random starting points permit a more rigorous assessment of convergence, and we developed two novel statistics, delta and epsilon, for this purpose. Although likelihood values invariably stabilized quickly, adequate s ling of the posterior distribution of tree topologies took considerably longer. Our results suggest that multimodality is common for data sets with 30 or more taxa and that this results in slow convergence and mixing. However, we also found that the pragmatic approach of combining data from several short, replicated runs into a "metachain" to estimate bipartition posterior probabilities provided good approximations, and that such estimates were no worse in approximating a reference posterior distribution than those obtained using a single long run of the same length as the metachain. Precision appears to be best when heated Markov chains have low temperatures, whereas chains with high temperatures appear to s le trees with high posterior probabilities only rarely.
Publisher: Oxford University Press (OUP)
Date: 24-04-2012
DOI: 10.1093/NAR/GKS335
Publisher: Wiley
Date: 17-09-2018
DOI: 10.1111/MEC.14849
Abstract: Conservation of exploited species requires an understanding of both genetic ersity and the dominant structuring forces, particularly near range limits, where climatic variation can drive rapid expansions or contractions of geographic range. Here, we examine population structure and landscape associations in Atlantic salmon (Salmo salar) across a heterogeneous landscape near the northern range limit in Labrador, Canada. Analysis of two licon-based data sets containing 101 microsatellites and 376 single nucleotide polymorphisms (SNPs) from 35 locations revealed clear differentiation between populations spawning in rivers flowing into a large marine embayment (Lake Melville) compared to coastal populations. The mechanisms influencing the differentiation of embayment populations were investigated using both multivariate and machine-learning landscape genetic approaches. We identified temperature as the strongest correlate with genetic structure, particularly warm temperature extremes and wider annual temperature ranges. The genomic basis of this ergence was further explored using a subset of locations (n = 17) and a 220K SNP array. SNPs associated with spatial structuring and temperature mapped to a erse set of genes and molecular pathways, including regulation of gene expression, immune response, and cell development and differentiation. The results spanning molecular marker types and both novel and established methods clearly show climate-associated, fine-scale population structure across an environmental gradient in Atlantic salmon near its range limit in North America, highlighting valuable approaches for predicting population responses to climate change and managing species sustainability.
Publisher: Wiley
Date: 14-09-2017
DOI: 10.1111/EVA.12524
Publisher: Wiley
Date: 11-03-2018
DOI: 10.1111/EVA.12606
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: Oxford University Press (OUP)
Date: 21-08-2012
Abstract: Environmental drivers of bio ersity can be identified by relating patterns of community similarity to ecological factors. Community variation has traditionally been assessed by considering changes in species composition and more recently by incorporating phylogenetic information to account for the relative similarity of taxa. Here, we describe how an important class of measures including Bray-Curtis, Canberra, and UniFrac can be extended to allow community variation to be computed on a phylogenetic network. We focus on phylogenetic split systems, networks that are produced by the widely used median network and neighbor-net methods, which can represent incongruence in the evolutionary history of a set of taxa. Calculating β ersity over a split system provides a measure of community similarity averaged over uncertainty or conflict in the available phylogenetic signal. Our freely available software, Network Diversity, provides 11 qualitative (presence-absence, unweighted) and 14 quantitative (weighted) network-based measures of community similarity that model different aspects of community richness and evenness. We demonstrate the broad applicability of network-based ersity approaches by applying them to three distinct data sets: pneumococcal isolates from distinct geographic regions, human mitochondrial DNA data from the Indonesian island of Nias, and proteorhodopsin sequences from the Sargasso and Mediterranean Seas. Our results show that major expected patterns of variation for these data sets are recovered using network-based measures, which indicates that these patterns are robust to phylogenetic uncertainty and conflict. Nonetheless, network-based measures of community similarity can differ substantially from measures ignoring phylogenetic relationships or from tree-based measures when incongruent signals are present in the underlying data. Network-based measures provide a methodology for assessing the robustness of β- ersity results in light of incongruent phylogenetic signal and allow β ersity to be calculated over widely used network structures such as median networks.
Publisher: Oxford University Press (OUP)
Date: 03-02-2010
DOI: 10.1093/BIOINFORMATICS/BTQ041
Abstract: Motivation: Metagenomics is the study of genetic material recovered directly from environmental s les. Taxonomic and functional differences between metagenomic s les can highlight the influence of ecological factors on patterns of microbial life in a wide range of habitats. Statistical hypothesis tests can help us distinguish ecological influences from s ling artifacts, but knowledge of only the P-value from a statistical hypothesis test is insufficient to make inferences about biological relevance. Current reporting practices for pairwise comparative metagenomics are inadequate, and better tools are needed for comparative metagenomic analysis. Results: We have developed a new software package, STAMP, for comparative metagenomics that supports best practices in analysis and reporting. Examination of a pair of iron mine metagenomes demonstrates that deeper biological insights can be gained using statistical techniques available in our software. An analysis of the functional potential of ‘Candidatus Accumulibacter phosphatis’ in two enhanced biological phosphorus removal metagenomes identified several subsystems that differ between the A.phosphatis stains in these related communities, including phosphate metabolism, secretion and metal transport. Availability: Python source code and binaries are freely available from our website at kiwi.cs.dal.ca/Software/STAMP Contact: beiko@cs.dal.ca Supplementary information: Supplementary data are available at Bioinformatics online.
Publisher: The Royal Society
Date: 12-08-2009
Abstract: Lateral genetic transfer (LGT) is an important adaptive force in evolution, contributing to metabolic, physiological and ecological innovation in most prokaryotes and some eukaryotes. Genomic sequences and other data have begun to illuminate the processes, mechanisms, quantitative extent and impact of LGT in erse organisms, populations, taxa and environments deep questions are being posed, and the provisional answers sometimes challenge existing paradigms. At the same time, there is an enhanced appreciation of the imperfections, biases and blind spots in the data and in analytical approaches. Here we identify and consider significant open questions concerning the role of LGT in genome evolution.
Publisher: Public Library of Science (PLoS)
Date: 22-09-2009
No related grants have been discovered for Robert Beiko.