Paul M K Gordon

The University of Calgary, Calgary, Alberta, Canada

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Publications (45)123.84 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Familial restrictive cardiomyopathy (RCM) caused by a single gene mutation is the least common of the inherited cardiomyopathies. Only a few RCM-causing mutations have been described. Most mutations causing RCM are located in sarcomere protein genes which also cause hypertrophic cardiomyopathy (HCM). Other genes associated with RCM include the desmin and familial amyloidosis genes. In the present study we describe familial RCM with severe heart failure triggered by a de novo mutation in TTN, encoding the huge muscle filament protein titin. Family members underwent physical examination, ECG and Doppler echocardiogram studies. The family comprised 6 affected individuals aged 12-35years. Linkage to candidate loci was performed, followed by gene sequencing. Candidate loci/gene analysis excluded 18 candidate genes but showed segregation with a common haplotype surrounding the TTN locus. Sequence analysis identified a de novo mutation within exon 266 of the TTN gene, resulting in the replacement of tyrosine by cysteine. p.Y7621C affects a highly conserved region in the protein within a fibronectin-3 domain, belonging to the A/I junction region of titin. No other disease-causing mutation was identified in cardiomyopathy genes by whole exome sequencing. Our study shows, for the first time, that mutations in TTN can cause restrictive cardiomyopathy. The giant filament titin is considered to be a determinant of a resting tension of the sarcomere and this report provides genetic evidence of its crucial role in diastolic function.
    International journal of cardiology 11/2013; · 7.08 Impact Factor
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    ABSTRACT: To investigate the role of gene localization and genome organization in cell-cell signalling and regulation, we mapped the distribution pattern of gene families that comprise core components of intercellular communication networks. Our study is centered on the distinct evolutionarily conserved metazoan signalling pathways that employ proteins in the receptor tyrosine kinase, WNT, hedgehog, NOTCH, Janus kinase/STAT, transforming growth factor beta, and nuclear hormone receptor protein families. Aberrant activity of these signalling pathways is closely associated with the promotion and maintenance of human cancers. The cataloguing and mapping of genes encoding these signalling proteins and comparisons across species has led us to propose that the genome can be subdivided into six genome-wide primary linkage groups (PLGs). PLGs are composed of assemblages of gene families that are often mutually exclusive, raising the possibility of unique functional identities for each group. Examination of the localization patterns of genes with distinct functions in signal transduction demonstrates dichotomous segregation patterns. For example, gene families of cell-surface receptors localize to genomic compartments that are distinct from the locations of their cognate ligand gene families. Additionally, genes encoding negative-acting components of signalling pathways (inhibitors and antagonists) are topologically separated from their positive regulators and other signal transducer genes. We, therefore, propose the existence of conserved genomic territories that encode key proteins required for the proper activity of metazoan signaling and regulatory systems. Disruption in this pattern of topologic genomic organization may contribute to aberrant regulation in hereditary or acquired diseases such as cancer. We further propose that long-range looping genomic regulatory interactions may provide a mechanism favouring the remarkable retention of these conserved gene clusters during chordate evolution.
    Genome 04/2013; 56(4):215-225. · 1.65 Impact Factor
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    ABSTRACT: BACKGROUND: BioHackathon 2010 was the third in a series of meetings hosted by the Database Center for Life Sciences (DBCLS) in Tokyo, Japan. The overall goal of the BioHackathon series is to improve the quality and accessibility of life science research data on the Web by bringing together representatives from public databases, analytical tool providers, and cyber-infrastructure researchers to jointly tackle important challenges in the area of in silico biological research. RESULTS: The theme of BioHackathon 2010 was the 'Semantic Web', and all attendees gathered with the shared goal of producing Semantic Web data from their respective resources, and/or consuming or interacting those data using their tools and interfaces. We discussed on topics including guidelines for designing semantic data and interoperability of resources. We consequently developed tools and clients for analysis and visualization. CONCLUSION: We provide a meeting report from BioHackathon 2010, in which we describe the discussions, decisions, and breakthroughs made as we moved towards compliance with Semantic Web technologies - from source provider, through middleware, to the end-consumer.
    Journal of biomedical semantics. 02/2013; 4(1):6.
  • Jung Soh, Paul M K Gordon, Christoph W Sensen
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    ABSTRACT: The Bluejay genome browser is a stand-alone visualization tool for the multi-scale viewing of annotated genomes and other genomic elements. Bluejay allows users to customize display features to suit their needs, and produces publication-quality graphics. Bluejay provides a multitude of ways to interrelate biological data at the genome scale. Users can load gene expression data into a genome display for expression visualization in context. Multiple genomes can be compared concurrently, including time series expression data, based on Gene Ontology labels. External, context-sensitive biological Web Services are linked to the displayed genomic elements ad hoc for in-depth genomic data analysis and interpretation. Users can mark multiple points of interest in a genome by creating waypoints, and exploit them for easy navigation of single or multiple genomes. Using this comprehensive visual environment, users can study a gene not just in relation to its genome, but also its transcriptome and evolutionary origins. Written in Java, Bluejay is platform-independent and is freely available from http://bluejay.ucalgary.ca.
    Current protocols in bioinformatics / editoral board, Andreas D. Baxevanis ... [et al.] 03/2012; Chapter 10:Unit10.9.
  • Paul M. K. Gordon, Ken Barker, Christoph W. Sensen
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    ABSTRACT: Programming-by-example (PbE) as a technique can only make substantial progress by addressing the open problem commonly known as the Semantic Gap. This gap is the discrepancy between what the user intended by their actions, and how the inference engine generalizes the actions for reuse in a program. The Seahawk/Daggoo PbE system attempts to close this gap in a novel way: by using Semantic Web and Web Service resources as the building blocks the user manipulates during the demonstration stage of PbE. This eliminates the need for PbE inference by leveraging domain-specific Web Services and community-based agreements about data meanings. The semantic gap in PbE is closed a priori because of semantic agreement between users and service providers within a domain. The new PbE system has been tested in the domain of Bioinformatics to create Web Service workflows, with justification and results reported here. Fundamentally, Seahawk/Daggoo is domain-agnostics because semantics are defined in Web-based ontologies rather than by the PbE system itself. Novel action-to-workflow concept mappings are also introduced.
    IEEE Symposium on Visual Languages and Human-Centric Computing, VL/HCC 2010, Leganés-Madrid, Spain, 21-25 September 2010, Proceedings; 01/2010
  • Paul M. K. Gordon, Ken Barker, Christoph W. Sensen
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    ABSTRACT: Seahawk is a browser for Moby Web services, which are online tools using a shared semantic registry and data formats. To make a wider array of tools available within Seahawk, the Daggoo system helps users adapt forms on existing Web sites to Moby’s specifications. Biologists were interviewed and given workflow design tasks, which revealed the types of tools present in their conceptual analysis workflows, and the types of control flow they understood. These observations were used to enhance Seahawk so that Moby and external Web tools can be browsed to create workflows "by demonstration". A flow-up user study measured how effectively biologists could 1) demonstrate a workflow for a realistic task, 2) understand the automatically generated workflow, and 3) use the workflow in the Taverna workflow editor/enactor. The results show promise that biologists without programming experience can become self-sufficient in analysis automation, using workflow-by-demonstration as a first step.
    Data Integration in the Life Sciences, 7th International Conference, DILS 2010, Gothenburg, Sweden, August 25-27, 2010. Proceedings; 01/2010
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    ABSTRACT: Anaerobranca gottschalkii strain LBS3 T is an extremophile living at high temperature (up to 65 degrees C) and in alkaline environments (up to pH 10.5). An assembly of 696 DNA contigs representing about 96% of the 2.26-Mbp genome of A. gottschalkii has been generated with a low-sequence-coverage shotgun-sequencing strategy. The chosen sequencing strategy provided rapid and economical access to genes encoding key enzymes of the mono- and polysaccharide metabolism, without dilution of spare resources for extensive sequencing of genes lacking potential economical value. Five of these amylolytic enzymes of considerable commercial interest for biotechnological applications have been expressed and characterized in more detail after identification of their genes in the partial genome sequence: type I pullulanase, cyclodextrin glycosyltransferase (CGTase), two alpha-amylases (AmyA and AmyB), and an alpha-1,4-glucan-branching enzyme.
    Journal of Molecular Microbiology and Biotechnology 02/2009; 16(1-2):81-90. · 1.95 Impact Factor
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    ABSTRACT: To gain insight into the disease progression of transmissible spongiform encephalopathies (TSE), we searched for disease-specific patterns in circulating nucleic acids (CNA) in elk and cattle. In a 25-month time-course experiment, CNAs were isolated from blood samples of 24 elk (Cervus elaphus) orally challenged with chronic wasting disease (CWD) infectious material. In a separate experiment, blood-sample CNAs from 29 experimental cattle (Bos taurus) 40 months post-inoculation with clinical bovine spongiform encephalopathy (BSE) were analyzed according to the same protocol. Next-generation sequencing provided broad elucidation of sample CNAs: we detected infection-specific sequences as early as 11 months in elk (i.e. at least 3 months before the appearance of the first clinical signs) and we established CNA patterns related to BSE in cattle at least 4 months prior to clinical signs. In elk, a progression of CNA sequence patterns was found to precede and correlate with macro-observable disease progression, including delayed CWD progression in elk with PrP genotype LM. Some of the patterns identified contain transcription-factor-binding sites linked to endogenous retroviral integration. These patterns suggest that retroviruses may be connected to the manifestation of TSEs. Our results may become useful for the early diagnosis of TSE in live elk and cattle.
    Nucleic Acids Research 01/2009; 37(2):550-6. · 8.28 Impact Factor
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    ABSTRACT: The INhibitor of Growth (ING) family of type II tumor suppressors (ING1-ING5) is involved in many cellular processes such as cell aging, apoptosis, DNA repair and tumorigenesis. To expand our understanding of the proteins with which the ING proteins interact, we designed a method that did not depend upon large-scale proteomics-based methods, since they may fail to highlight transient or relatively weak interactions. Here we test a cross-species (yeast, fly, and human) bioinformatics-based approach to identify potential human ING-interacting proteins with higher probability and accuracy than approaches based on screens in a single species. We confirm the validity of this screen and show that ING1 interacts specifically with three of the three proteins tested; p38MAPK, MEKK4 and RAD50. These novel ING-interacting proteins further link ING proteins to cell stress and DNA damage signaling, providing previously unknown upstream links to DNA damage response pathways in which ING1 participates. The bioinformatics approach we describe can be used to create an interaction prediction list for any human proteins with yeast homolog(s). None of the validated interactions were predicted by the conventional protein-protein interaction tools we tested. Validation of our approach by traditional laboratory techniques shows that we can extract value from the voluminous weak interaction data already elucidated in yeast and fly databases. We therefore propose that the weak (low signal to noise ratio) data from large-scale interaction datasets are currently underutilized.
    BMC Genomics 10/2008; 9:426. · 4.40 Impact Factor
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    ABSTRACT: The BioMoby project was initiated in 2001 from within the model organism database community. It aimed to standardize methodologies to facilitate information exchange and access to analytical resources, using a consensus driven approach. Six years later, the BioMoby development community is pleased to announce the release of the 1.0 version of the interoperability framework, registry Application Programming Interface and supporting Perl and Java code-bases. Together, these provide interoperable access to over 1400 bioinformatics resources worldwide through the BioMoby platform, and this number continues to grow. Here we highlight and discuss the features of BioMoby that make it distinct from other Semantic Web Service and interoperability initiatives, and that have been instrumental to its deployment and use by a wide community of bioinformatics service providers. The standard, client software, and supporting code libraries are all freely available at http://www.biomoby.org/.
    Briefings in Bioinformatics 06/2008; 9(3):220-31. · 5.30 Impact Factor
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    ABSTRACT: The genome sequence of the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough was reanalyzed to design unique 70-mer oligonucleotide probes against 2,824 probable protein-coding regions. These included three genes not previously annotated, including one that encodes a c-type cytochrome. Using microarrays printed with these 70-mer probes, we analyzed the gene expression profile of wild-type D. vulgaris grown on cathodic hydrogen, generated at an iron electrode surface with an imposed negative potential of -1.1 V (cathodic protection conditions). The gene expression profile of cells grown on cathodic hydrogen was compared to that of cells grown with gaseous hydrogen bubbling through the culture. Relative to the latter, the electrode-grown cells overexpressed two hydrogenases, the hyn-1 genes for [NiFe] hydrogenase 1 and the hyd genes, encoding [Fe] hydrogenase. The hmc genes for the high-molecular-weight cytochrome complex, which allows electron flow from the hydrogenases across the cytoplasmic membrane, were also overexpressed. In contrast, cells grown on gaseous hydrogen overexpressed the hys genes for [NiFeSe] hydrogenase. Cells growing on the electrode also overexpressed genes encoding proteins which promote biofilm formation. Although the gene expression profiles for these two modes of growth were distinct, they were more closely related to each other than to that for cells grown in a lactate- and sulfate-containing medium. Electrochemically measured corrosion rates were lower for iron electrodes covered with hyn-1, hyd, and hmc mutant biofilms than for wild-type biofilms. This confirms the importance, suggested by the gene expression studies, of the corresponding gene products in D. vulgaris-mediated iron corrosion.
    Applied and environmental microbiology 05/2008; 74(8):2404-13. · 3.69 Impact Factor
  • 03/2008: pages 379 - 397; , ISBN: 9783527620876
  • 01/2008: pages 383 - 414; , ISBN: 9783527619733
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    ABSTRACT: In order to characterize the genome-wide transcriptional response of the hyperthermophilic, aerobic crenarchaeote Sulfolobus solfataricus to UV damage, we used high-density DNA microarrays which covered 3,368 genetic features encoded on the host genome, as well as the genes of several extrachromosomal genetic elements. While no significant up-regulation of genes potentially involved in direct DNA damage reversal was observed, a specific transcriptional UV response involving 55 genes could be dissected. Although flow cytometry showed only modest perturbation of the cell cycle, strong modulation of the transcript levels of the Cdc6 replication initiator genes was observed. Up-regulation of an operon encoding Mre11 and Rad50 homologs pointed to induction of recombinational repair. Consistent with this, DNA double-strand breaks were observed between 2 and 8 h after UV treatment, possibly resulting from replication fork collapse at damaged DNA sites. The strong transcriptional induction of genes which potentially encode functions for pilus formation suggested that conjugational activity might lead to enhanced exchange of genetic material. In support of this, a statistical microscopic analysis demonstrated that large cell aggregates formed upon UV exposure. Together, this provided supporting evidence to a link between recombinational repair and conjugation events.
    Journal of bacteriology 01/2008; 189(23):8708-18. · 3.94 Impact Factor
  • Paul M. K. Gordon, Christoph W. Sensen
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    ABSTRACT: Semantic annotations for WSDL (SAWSDL) is a recently adopted W3C recommendation that provides a mechanism by which WSDL documents can reference external, domain-specific semantic models in order to provide concept-level interoperability of Web Services. Moby is an established protocol for providing semantic Web Services developed by the bioinformatics community: we use Moby to provide a grounding for a SAWSDL implementation in bioinformatics. Our software (Daggoo) allows users to create Moby-compliant semantic Web Services by simply adding SAWSDL markup to existing WSDL files. These new services are compatible with existing Moby services and client software. The Java software we present consists of a proxy servlet, a URI-resolution mechanism, and rule systems for converting back and forth between Moby and XML Schema data formats. As an early implementation of SAWSDL, Daggoo reveals shortcomings in the notation, and several additional technologies needed to achieve real-world semantic interoperability of WSDL-based services. Based on our experience, we suggest how to improve the semantic annotation mechanism, and how to reduce the programming burden for individual service providers. Furthermore, we demonstrate the importance of a semantically-enabled registry for services and data types in facilitating scientist-driven, rather than programmer-driven, Web service choreography.
    2008 IEEE International Conference on Web Services (ICWS 2008), September 23-26, 2008, Beijing, China; 01/2008
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    ABSTRACT: The spindle-shaped Sulfolobus virus SSV1 was the first of a series of unusual and uniquely shaped viruses isolated from hyperthermophilic Archaea. Using whole-genome microarrays we show here that the circular 15.5 kb DNA genome of SSV1 exhibits a chronological regulation of its transcription upon UV irradiation, reminiscent to the life cycles of bacteriophages and eukaryotic viruses. The transcriptional cycle starts with a small UV-specific transcript and continues with early transcripts on both its flanks. The late transcripts appear after the onset of viral replication and are extended to their full lengths towards the end of the approximately 8.5 h cycle. While we detected only small differences in genome-wide analysis of the host Sulfolobus solfataricus comparing infected versus uninfected strains, we found a marked difference with respect to the strength and speed of the general UV response of the host. Models for the regulation of the virus cycle, and putative functions of genes in SSV1 are presented.
    Virology 09/2007; 365(1):48-59. · 3.37 Impact Factor
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    Paul M K Gordon, Quang Trinh, Christoph W Sensen
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    ABSTRACT: Several semantic Web Services clients for Bioinformatics have been released, but to date no support systems for service providers have been described. We have created a framework ('MobyServlet') that very simply allows an existing Java application to conform to the MOBY-S semantic Web Services protocol. Using an existing Java program for codon-pair bias determination as an example, we enumerate the steps required for MOBY-S compliance. With minimal programming effort, such a deployment has the advantages of: (1) wider exposure to the user community by automatic inclusion in all MOBY-S client programs and (2) automatic interoperability with other MOBY-S services for input and output. Complex on-line analysis will become easier for biologists as more developers adopt MOBY-S. AVAILABILITY: The framework and documentation are freely available from the Java developer's section of http://www.biomoby.org/.
    Bioinformatics 06/2007; 23(9):1178-80. · 5.47 Impact Factor
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    ABSTRACT: Elicitor-induced sanguinarine accumulation in opium poppy (Papaver somniferum) cell cultures provides a responsive model system to profile modulations in gene transcripts and metabolites related to alkaloid biosynthesis. An annotated expressed sequence tag (EST) database was assembled from 10,224 random clones isolated from an elicitor-treated opium poppy cell culture cDNA library. The most abundant ESTs encoded defense proteins, and enzymes involved in alkaloid metabolism and S-adenosylmethionine-dependent methyl transfer. ESTs corresponding to 40 enzymes involved in the conversion of sucrose to sanguinarine were identified. A corresponding DNA microarray was probed with RNA from cell cultures collected at various time-points after elicitor treatment, and compared with RNA from control cells. Several diverse transcript populations were coordinately induced, with alkaloid biosynthetic enzyme and defense protein transcripts displaying the most rapid and substantial increases. In addition to all known sanguinarine biosynthetic gene transcripts, mRNAs encoding several upstream primary metabolic enzymes were coordinately induced. Fourier transform-ion cyclotron resonance-mass spectrometry was used to characterize the metabolite profiles of control and elicitor-treated cell cultures. Principle component analysis revealed a significant and dynamic separation in the metabolome, represented by 992 independent detected analytes, in response to elicitor treatment. Identified metabolites included sanguinarine, dihydrosanguinarine, and the methoxylated derivatives dihydrochelirubine and chelirubine, and the alkaloid pathway intermediates N-methylcoclaurine, N-methylstylopine, and protopine. Some of the detected analytes showed temporal changes in abundance consistent with modulations in the profiles of alkaloid biosynthetic gene transcripts.
    Planta 05/2007; 225(5):1085-106. · 3.35 Impact Factor
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    Paul M K Gordon, Christoph W Sensen
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    ABSTRACT: Traditional HTML interfaces for input to and output from Bioinformatics analysis on the Web are highly variable in style, content and data formats. Combining multiple analyses can therefore be an onerous task for biologists. Semantic Web Services allow automated discovery of conceptual links between remote data analysis servers. A shared data ontology and service discovery/execution framework is particularly attractive in Bioinformatics, where data and services are often both disparate and distributed. Instead of biologists copying, pasting and reformatting data between various Web sites, Semantic Web Service protocols such as MOBY-S hold out the promise of seamlessly integrating multi-step analysis. We have developed a program (Seahawk) that allows biologists to intuitively and seamlessly chain together Web Services using a data-centric, rather than the customary service-centric approach. The approach is illustrated with a ferredoxin mutation analysis. Seahawk concentrates on lowering entry barriers for biologists: no prior knowledge of the data ontology, or relevant services is required. In stark contrast to other MOBY-S clients, in Seahawk users simply load Web pages and text files they already work with. Underlying the familiar Web-browser interaction is an XML data engine based on extensible XSLT style sheets, regular expressions, and XPath statements which import existing user data into the MOBY-S format. As an easily accessible applet, Seahawk moves beyond standard Web browser interaction, providing mechanisms for the biologist to concentrate on the analytical task rather than on the technical details of data formats and Web forms. As the MOBY-S protocol nears a 1.0 specification, we expect more biologists to adopt these new semantic-oriented ways of doing Web-based analysis, which empower them to do more complicated, ad hoc analysis workflow creation without the assistance of a programmer.
    BMC Bioinformatics 02/2007; 8:208. · 3.02 Impact Factor
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    ABSTRACT: Many questions that biologists want to answer using the information available from completely sequenced genomes are complex. A graphical environment allows users to visually explore and operate on a sequence. Sequence and annotation data exists in bewildering varieties of types and levels of detail. The graphical environment therefore needs to adapt to this variation to provide the user the best possible visual representation of genomic data in a given context. As more and more online tools and services become available for biologists, mediating software should also be able to integrate and link to them. The Bluejay browser is a Java-based visual environment for exploring biological sequences. Uniquely, Bluejay fully integrates existing gene expression software into a genomic context. Bluejay also differentiates itself from most form-based HTML sequence browsers because it: (i) is highly scalable so that it can visualize a wide range of genomic objects ranging from a large whole genome down to individual nucleotides by using data-transformational Web services; and (ii) dynamically discovers and provides links to disparate resources such as gene annotation data (via XLinks) and semantically- described biological Web Services (via the BioMOBY protocol).
    2007 IEEE International Conference on Services Computing - Workshops (SCW 2007), 9-13 July 2007, Salt Lake City, Utah, USA; 01/2007

Publication Stats

1k Citations
123.84 Total Impact Points

Institutions

  • 2003–2012
    • The University of Calgary
      • • Faculty of Medicine
      • • Department of Biochemistry and Molecular Biology
      Calgary, Alberta, Canada
  • 2007
    • University of Bergen
      • Department of Biology
      Bergen, Hordaland Fylke, Norway
  • 2000–2001
    • The Rockefeller University
      New York City, New York, United States
    • University of Ottawa
      • Department of Biology
      Ottawa, Ontario, Canada
    • Université Paris-Sud 11
      • Institut de Génétique et Microbiologie (IGMORS)
      Paris, Ile-de-France, France