Publications by authors named "Marcus C Chibucos"

31 Publications

Phenotype annotation with the ontology of microbial phenotypes (OMP).

J Biomed Semantics 2019 07 15;10(1):13. Epub 2019 Jul 15.

Department of Biochemistry and Biophysics, Texas A&M University and Texas AgriLife Research, College Station, TX, USA.

Background: Microbial genetics has formed a foundation for understanding many aspects of biology. Systematic annotation that supports computational data mining should reveal further insights for microbes, microbiomes, and conserved functions beyond microbes. The Ontology of Microbial Phenotypes (OMP) was created to support such annotation.

Results: We define standards for an OMP-based annotation framework that supports the capture of a variety of phenotypes and provides flexibility for different levels of detail based on a combination of pre- and post-composition using OMP and other Open Biomedical Ontology (OBO) projects. A system for entering and viewing OMP annotations has been added to our online, public, web-based data portal.

Conclusions: The annotation framework described here is ready to support projects to capture phenotypes from the experimental literature for a variety of microbes. Defining the OMP annotation standard should support the development of new software tools for data mining and analysis in comparative phenomics.
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http://dx.doi.org/10.1186/s13326-019-0205-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631659PMC
July 2019

Annotation of gene product function from high-throughput studies using the Gene Ontology.

Database (Oxford) 2019 01 1;2019. Epub 2019 Jan 1.

Zebrafish Information Network, University of Oregon, Eugene, OR, USA.

High-throughput studies constitute an essential and valued source of information for researchers. However, high-throughput experimental workflows are often complex, with multiple data sets that may contain large numbers of false positives. The representation of high-throughput data in the Gene Ontology (GO) therefore presents a challenging annotation problem, when the overarching goal of GO curation is to provide the most precise view of a gene's role in biology. To address this, representatives from annotation teams within the GO Consortium reviewed high-throughput data annotation practices. We present an annotation framework for high-throughput studies that will facilitate good standards in GO curation and, through the use of new high-throughput evidence codes, increase the visibility of these annotations to the research community.
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http://dx.doi.org/10.1093/database/baz007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355445PMC
January 2019

ECO, the Evidence & Conclusion Ontology: community standard for evidence information.

Nucleic Acids Res 2019 01;47(D1):D1186-D1194

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

The Evidence and Conclusion Ontology (ECO) contains terms (classes) that describe types of evidence and assertion methods. ECO terms are used in the process of biocuration to capture the evidence that supports biological assertions (e.g. gene product X has function Y as supported by evidence Z). Capture of this information allows tracking of annotation provenance, establishment of quality control measures and query of evidence. ECO contains over 1500 terms and is in use by many leading biological resources including the Gene Ontology, UniProt and several model organism databases. ECO is continually being expanded and revised based on the needs of the biocuration community. The ontology is freely available for download from GitHub (https://github.com/evidenceontology/) or the project's website (http://evidenceontology.org/). Users can request new terms or changes to existing terms through the project's GitHub site. ECO is released into the public domain under CC0 1.0 Universal.
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http://dx.doi.org/10.1093/nar/gky1036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323956PMC
January 2019

Vaginal Candida spp. genomes from women with vulvovaginal candidiasis.

Pathog Dis 2017 08;75(6)

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201 USA.

Candida albicans is the predominant cause of vulvovaginal candidiasis (VVC). Little is known regarding the genetic diversity of Candida spp. in the vagina or the microvariations in strains over time that may contribute to the development of VVC. This study reports the draft genome sequences of four C. albicans and one C. glabrata strains isolated from women with VVC. An SNP-based whole-genome phylogeny indicates that these isolates are closely related; however, phylogenetic distances between them suggest that there may be genetic adaptations driven by unique host environments. These sequences will facilitate further comparative analyses and ultimately improve our understanding of genetic variation in isolates of Candida spp. that are associated with VVC.
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http://dx.doi.org/10.1093/femspd/ftx061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827580PMC
August 2017

The Evidence and Conclusion Ontology (ECO): Supporting GO Annotations.

Methods Mol Biol 2017 ;1446:245-259

Department of Medicine, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

The Evidence and Conclusion Ontology (ECO) is a community resource for describing the various types of evidence that are generated during the course of a scientific study and which are typically used to support assertions made by researchers. ECO describes multiple evidence types, including evidence resulting from experimental (i.e., wet lab) techniques, evidence arising from computational methods, statements made by authors (whether or not supported by evidence), and inferences drawn by researchers curating the literature. In addition to summarizing the evidence that supports a particular assertion, ECO also offers a means to document whether a computer or a human performed the process of making the annotation. Incorporating ECO into an annotation system makes it possible to leverage the structure of the ontology such that associated data can be grouped hierarchically, users can select data associated with particular evidence types, and quality control pipelines can be optimized. Today, over 30 resources, including the Gene Ontology, use the Evidence and Conclusion Ontology to represent both evidence and how annotations are made.
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http://dx.doi.org/10.1007/978-1-4939-3743-1_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377151PMC
December 2017

Annotated draft genome sequences of three species of Cryptosporidium: Cryptosporidium meleagridis isolate UKMEL1, C. baileyi isolate TAMU-09Q1 and C. hominis isolates TU502_2012 and UKH1.

Pathog Dis 2016 10 12;74(7). Epub 2016 Aug 12.

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

Human cryptosporidiosis is caused primarily by Cryptosporidium hominis, C. parvum and C. meleagridis. To accelerate research on parasites in the genus Cryptosporidium, we generated annotated, draft genome sequences of human C. hominis isolates TU502_2012 and UKH1, C. meleagridis UKMEL1, also isolated from a human patient, and the avian parasite C. baileyi TAMU-09Q1. The annotation of the genome sequences relied in part on RNAseq data generated from the oocyst stage of both C. hominis and C. baileyi The genome assembly of C. hominis is significantly more complete and less fragmented than that available previously, which enabled the generation of a much-improved gene set for this species, with an increase in average gene length of 500 bp relative to the protein-encoding genes in the 2004 C. hominis annotation. Our results reveal that the genomes of C. hominis and C. parvum are very similar in both gene density and average gene length. These data should prove a valuable resource for the Cryptosporidium research community.
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http://dx.doi.org/10.1093/femspd/ftw080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407061PMC
October 2016

An integrated genomic and transcriptomic survey of mucormycosis-causing fungi.

Nat Commun 2016 07 22;7:12218. Epub 2016 Jul 22.

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.

Mucormycosis is a life-threatening infection caused by Mucorales fungi. Here we sequence 30 fungal genomes, and perform transcriptomics with three representative Rhizopus and Mucor strains and with human airway epithelial cells during fungal invasion, to reveal key host and fungal determinants contributing to pathogenesis. Analysis of the host transcriptional response to Mucorales reveals platelet-derived growth factor receptor B (PDGFRB) signaling as part of a core response to divergent pathogenic fungi; inhibition of PDGFRB reduces Mucorales-induced damage to host cells. The unique presence of CotH invasins in all invasive Mucorales, and the correlation between CotH gene copy number and clinical prevalence, are consistent with an important role for these proteins in mucormycosis pathogenesis. Our work provides insight into the evolution of this medically and economically important group of fungi, and identifies several molecular pathways that might be exploited as potential therapeutic targets.
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http://dx.doi.org/10.1038/ncomms12218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961843PMC
July 2016

The Ontology for Biomedical Investigations.

PLoS One 2016 29;11(4):e0154556. Epub 2016 Apr 29.

University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource (http://obi-ontology.org) providing details on the people, policies, and issues being addressed in association with OBI. The current release of OBI is available at http://purl.obolibrary.org/obo/obi.owl.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154556PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851331PMC
April 2017

From data repositories to submission portals: rethinking the role of domain-specific databases in CollecTF.

Database (Oxford) 2016 25;2016. Epub 2016 Apr 25.

Department of Biological Sciences, University of Maryland Baltimore County (UMBC), 1000 Hilltop Circle, Baltimore, MD, 21250, USA

Domain-specific databases are essential resources for the biomedical community, leveraging expert knowledge to curate published literature and provide access to referenced data and knowledge. The limited scope of these databases, however, poses important challenges on their infrastructure, visibility, funding and usefulness to the broader scientific community. CollecTF is a community-oriented database documenting experimentally validated transcription factor (TF)-binding sites in the Bacteria domain. In its quest to become a community resource for the annotation of transcriptional regulatory elements in bacterial genomes, CollecTF aims to move away from the conventional data-repository paradigm of domain-specific databases. Through the adoption of well-established ontologies, identifiers and collaborations, CollecTF has progressively become also a portal for the annotation and submission of information on transcriptional regulatory elements to major biological sequence resources (RefSeq, UniProtKB and the Gene Ontology Consortium). This fundamental change in database conception capitalizes on the domain-specific knowledge of contributing communities to provide high-quality annotations, while leveraging the availability of stable information hubs to promote long-term access and provide high-visibility to the data. As a submission portal, CollecTF generates TF-binding site information through direct annotation of RefSeq genome records, definition of TF-based regulatory networks in UniProtKB entries and submission of functional annotations to the Gene Ontology. As a database, CollecTF provides enhanced search and browsing, targeted data exports, binding motif analysis tools and integration with motif discovery and search platforms. This innovative approach will allow CollecTF to focus its limited resources on the generation of high-quality information and the provision of specialized access to the data.Database URL: http://www.collectf.org/.
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http://dx.doi.org/10.1093/database/baw055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843526PMC
January 2017

Implementation of a Pan-Genomic Approach to Investigate Holobiont-Infecting Microbe Interaction: A Case Report of a Leukemic Patient with Invasive Mucormycosis.

PLoS One 2015 10;10(11):e0139851. Epub 2015 Nov 10.

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Disease can be conceptualized as the result of interactions between infecting microbe and holobiont, the combination of a host and its microbial communities. It is likely that genomic variation in the host, infecting microbe, and commensal microbiota are key determinants of infectious disease clinical outcomes. However, until recently, simultaneous, multiomic investigation of infecting microbe and holobiont components has rarely been explored. Herein, we characterized the infecting microbe, host, micro- and mycobiomes leading up to infection onset in a leukemia patient that developed invasive mucormycosis. We discovered that the patient was infected with a strain of the recently described Mucor velutinosus species which we determined was hypervirulent in a Drosophila challenge model and has a predisposition for skin dissemination. After completing the infecting M. velutinosus genome and genomes from four other Mucor species, comparative pathogenomics was performed and assisted in identifying 66 M. velutinosus-specific putatively secreted proteins, including multiple novel secreted aspartyl proteinases which may contribute to the unique clinical presentation of skin dissemination. Whole exome sequencing of the patient revealed multiple non-synonymous polymorphisms in genes critical to control of fungal proliferation, such as TLR6 and PTX3. Moreover, the patient had a non-synonymous polymorphism in the NOD2 gene and a missense mutation in FUT2, which have been linked to microbial dysbiosis and microbiome diversity maintenance during physiologic stress, respectively. In concert with host genetic polymorphism data, the micro- and mycobiome analyses revealed that the infection developed amid a dysbiotic microbiome with low α-diversity, dominated by staphylococci. Additionally, longitudinal mycobiome data showed that M. velutinosus DNA was detectable in oral samples preceding disease onset. Our genome-level study of the host-infecting microbe-commensal triad extends the concept of personalized genomic medicine to the holobiont-infecting microbe interface thereby offering novel opportunities for using synergistic genetic methods to increase understanding of infectious diseases pathogenesis and clinical outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0139851PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640583PMC
June 2016

The Confidence Information Ontology: a step towards a standard for asserting confidence in annotations.

Database (Oxford) 2015 9;2015:bav043. Epub 2015 May 9.

Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland, Department of Microbiology and Immunology and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD, USA, SIB Swiss Institute of Bioinformatics, 1 Rue Michel Servet, 1211 Geneva, Switzerland, Department of Medicine and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD, USA, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158, USA, School of Information, University of South Florida, Tampa, FL, 33647, USA, Genomics Division, Lawrence Berkeley National Lab, 1 Cyclotron Rd., Berkeley, 94720 CA USA, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK, Swiss-Prot Group, SIB Swiss Institute of Bioinformatics, Centre Medical Universitaire, Geneva, Switzerland, ETH Zurich, Department of Computer Science, Universitätstr. 19, 8092 Zürich, Switzerland, SIB Swiss Institute of Bioinformatics, Universitätstr. 6, 8092 Zürich, Switzerland and University College London, Gower St, London WC1E 6BT, UK Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland, Department of Microbiology and Immunology and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD, USA, SIB Swiss Institute of Bioinformatics, 1 Rue Michel Servet, 1211 Geneva, Switzerland, Department of Medicine and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD, USA, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158, USA, School of Information, University of South Florida, Tampa, FL, 33647, USA, Genomics Division, Lawrence Berkeley Nat

Biocuration has become a cornerstone for analyses in biology, and to meet needs, the amount of annotations has considerably grown in recent years. However, the reliability of these annotations varies; it has thus become necessary to be able to assess the confidence in annotations. Although several resources already provide confidence information about the annotations that they produce, a standard way of providing such information has yet to be defined. This lack of standardization undermines the propagation of knowledge across resources, as well as the credibility of results from high-throughput analyses. Seeded at a workshop during the Biocuration 2012 conference, a working group has been created to address this problem. We present here the elements that were identified as essential for assessing confidence in annotations, as well as a draft ontology--the Confidence Information Ontology--to illustrate how the problems identified could be addressed. We hope that this effort will provide a home for discussing this major issue among the biocuration community. Tracker URL: https://github.com/BgeeDB/confidence-information-ontology Ontology URL: https://raw.githubusercontent.com/BgeeDB/confidence-information-ontology/master/src/ontology/cio-simple.obo
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http://dx.doi.org/10.1093/database/bav043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425939PMC
December 2015

The genome sequence of four isolates from the family Lichtheimiaceae.

Pathog Dis 2015 Jul 9;73(5). Epub 2015 Apr 9.

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

This study reports the release of draft genome sequences of two isolates of Lichtheimia corymbifera and two isolates of L. ramosa. Phylogenetic analyses indicate that the two L. corymbifera strains (CDC-B2541 and 008-049) are closely related to the previously sequenced L. corymbifera isolate (FSU 9682) while our two L. ramosa strains CDC-B5399 and CDC-B5792 cluster apart from them. These genome sequences will further the understanding of intraspecies and interspecies genetic variation within the Mucoraceae family of pathogenic fungi.
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http://dx.doi.org/10.1093/femspd/ftv024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467520PMC
July 2015

An ontology for microbial phenotypes.

BMC Microbiol 2014 Nov 30;14:294. Epub 2014 Nov 30.

Institute for Genome Sciences and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: Phenotypic data are routinely used to elucidate gene function in organisms amenable to genetic manipulation. However, previous to this work, there was no generalizable system in place for the structured storage and retrieval of phenotypic information for bacteria.

Results: The Ontology of Microbial Phenotypes (OMP) has been created to standardize the capture of such phenotypic information from microbes. OMP has been built on the foundations of the Basic Formal Ontology and the Phenotype and Trait Ontology. Terms have logical definitions that can facilitate computational searching of phenotypes and their associated genes. OMP can be accessed via a wiki page as well as downloaded from SourceForge. Initial annotations with OMP are being made for Escherichia coli using a wiki-based annotation capture system. New OMP terms are being concurrently developed as annotation proceeds.

Conclusions: We anticipate that diverse groups studying microbial genetics and associated phenotypes will employ OMP for standardizing microbial phenotype annotation, much as the Gene Ontology has standardized gene product annotation. The resulting OMP resource and associated annotations will facilitate prediction of phenotypes for unknown genes and result in new experimental characterization of phenotypes and functions.
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http://dx.doi.org/10.1186/s12866-014-0294-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287307PMC
November 2014

Single molecule sequencing and genome assembly of a clinical specimen of Loa loa, the causative agent of loiasis.

BMC Genomics 2014 Sep 12;15:788. Epub 2014 Sep 12.

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: More than 20% of the world's population is at risk for infection by filarial nematodes and >180 million people worldwide are already infected. Along with infection comes significant morbidity that has a socioeconomic impact. The eight filarial nematodes that infect humans are Wuchereria bancrofti, Brugia malayi, Brugia timori, Onchocerca volvulus, Loa loa, Mansonella perstans, Mansonella streptocerca, and Mansonella ozzardi, of which three have published draft genome sequences. Since all have humans as the definitive host, standard avenues of research that rely on culturing and genetics have often not been possible. Therefore, genome sequencing provides an important window into understanding the biology of these parasites. The need for large amounts of high quality genomic DNA from homozygous, inbred lines; the availability of only short sequence reads from next-generation sequencing platforms at a reasonable expense; and the lack of random large insert libraries has limited our ability to generate high quality genome sequences for these parasites. However, the Pacific Biosciences single molecule, real-time sequencing platform holds great promise in reducing input amounts and generating sufficiently long sequences that bypass the need for large insert paired libraries.

Results: Here, we report on efforts to generate a more complete genome assembly for L. loa using genetically heterogeneous DNA isolated from a single clinical sample and sequenced on the Pacific Biosciences platform. To obtain the best assembly, numerous assemblers and sequencing datasets were analyzed, combined, and compared. Quiver-informed trimming of an assembly of only Pacific Biosciences reads by HGAP2 was selected as the final assembly of 96.4 Mbp in 2,250 contigs. This results in ~9% more of the genome in ~85% fewer contigs from ~80% less starting material at a fraction of the cost of previous Roche 454-based sequencing efforts.

Conclusions: The result is the most complete filarial nematode assembly produced thus far and demonstrates the utility of single molecule sequencing on the Pacific Biosciences platform for genetically heterogeneous metazoan genomes.
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http://dx.doi.org/10.1186/1471-2164-15-788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175631PMC
September 2014

Rapid transcriptome sequencing of an invasive pest, the brown marmorated stink bug Halyomorpha halys.

BMC Genomics 2014 Aug 29;15:738. Epub 2014 Aug 29.

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: Halyomorpha halys (Stål) (Insecta:Hemiptera;Pentatomidae), commonly known as the Brown Marmorated Stink Bug (BMSB), is an invasive pest of the mid-Atlantic region of the United States, causing economically important damage to a wide range of crops. Native to Asia, BMSB was first observed in Allentown, PA, USA, in 1996, and this pest is now well-established throughout the US mid-Atlantic region and beyond. In addition to the serious threat BMSB poses to agriculture, BMSB has become a nuisance to homeowners, invading home gardens and congregating in large numbers in human-made structures, including homes, to overwinter. Despite its significance as an agricultural pest with limited control options, only 100 bp of BMSB sequence data was available in public databases when this project began.

Results: Transcriptome sequencing was undertaken to provide a molecular resource to the research community to inform the development of pest control strategies and to provide molecular data for population genetics studies of BMSB. Using normalized, strand-specific libraries, we sequenced pools of all BMSB life stages on the Illumina HiSeq. Trinity was used to assemble 200,000 putative transcripts in >100,000 components. A novel bioinformatic method that analyzed the strand-specificity of the data reduced this to 53,071 putative transcripts from 18,573 components. By integrating multiple other data types, we narrowed this further to 13,211 representative transcripts.

Conclusions: Bacterial endosymbiont genes were identified in this dataset, some of which have a copy number consistent with being lateral gene transfers between endosymbiont genomes and Hemiptera, including ankyrin-repeat related proteins, lysozyme, and mannanase. Such genes and endosymbionts may provide novel targets for BMSB-specific biocontrol. This study demonstrates the utility of strand-specific sequencing in generating shotgun transcriptomes and that rapid sequencing shotgun transcriptomes is possible without the need for extensive inbreeding to generate homozygous lines. Such sequencing can provide a rapid response to pest invasions similar to that already described for disease epidemiology.
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http://dx.doi.org/10.1186/1471-2164-15-738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174608PMC
August 2014

Standardized description of scientific evidence using the Evidence Ontology (ECO).

Database (Oxford) 2014 22;2014. Epub 2014 Jul 22.

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA, Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA, Saccharomyces Genome Database, Department of Genetics, Stanford University, Stanford, CA 94305, USA, Computational Biology and Bioinformatics, The Jackson Laboratory, Bar Harbor, ME 04609, USA, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD UK, Department of Epidemiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USAInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA, Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA, Saccharomyces Genome Database, Department of Genetics, Stanford University, Stanford, CA 94305, USA, Computational Biology and Bioinformatics, The Jackson Laboratory, Bar Harbor, ME 04609, USA, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD UK, Department of Epidemiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

The Evidence Ontology (ECO) is a structured, controlled vocabulary for capturing evidence in biological research. ECO includes diverse terms for categorizing evidence that supports annotation assertions including experimental types, computational methods, author statements and curator inferences. Using ECO, annotation assertions can be distinguished according to the evidence they are based on such as those made by curators versus those automatically computed or those made via high-throughput data review versus single test experiments. Originally created for capturing evidence associated with Gene Ontology annotations, ECO is now used in other capacities by many additional annotation resources including UniProt, Mouse Genome Informatics, Saccharomyces Genome Database, PomBase, the Protein Information Resource and others. Information on the development and use of ECO can be found at http://evidenceontology.org. The ontology is freely available under Creative Commons license (CC BY-SA 3.0), and can be downloaded in both Open Biological Ontologies and Web Ontology Language formats at http://code.google.com/p/evidenceontology. Also at this site is a tracker for user submission of term requests and questions. ECO remains under active development in response to user-requested terms and in collaborations with other ontologies and database resources. Database URL: Evidence Ontology Web site: http://evidenceontology.org.
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http://dx.doi.org/10.1093/database/bau075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105709PMC
February 2015

Draft Genome Sequence of Mortierella alpina Isolate CDC-B6842.

Genome Announc 2014 Jan 23;2(1). Epub 2014 Jan 23.

Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

We report the draft genome sequence of Mortierella alpina isolate CDC-B6842. M. alpina is a nonpathogenic member of the Mucoromycotina subphylum of fungi that is an important model for understanding the molecular mechanisms of lipid production and metabolism.
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http://dx.doi.org/10.1128/genomeA.01180-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900895PMC
January 2014

Draft Genome Sequences of Human Pathogenic Fungus Geomyces pannorum Sensu Lato and Bat White Nose Syndrome Pathogen Geomyces (Pseudogymnoascus) destructans.

Genome Announc 2013 Dec 19;1(6). Epub 2013 Dec 19.

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.

We report the draft genome sequences of Geomyces pannorum sensu lato and Geomyces (Pseudogymnoascus) destructans. G. pannorum has a larger proteome than G. destructans, containing more proteins with ascribed enzymatic functions. This dichotomy in the genomes of related psychrophilic fungi is a valuable target for defining their distinct saprobic and pathogenic attributes.
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http://dx.doi.org/10.1128/genomeA.01045-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868853PMC
December 2013

Simultaneous transcriptional profiling of bacteria and their host cells.

PLoS One 2013 4;8(12):e80597. Epub 2013 Dec 4.

Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.

We developed an RNA-Seq-based method to simultaneously capture prokaryotic and eukaryotic expression profiles of cells infected with intracellular bacteria. As proof of principle, this method was applied to Chlamydia trachomatis-infected epithelial cell monolayers in vitro, successfully obtaining transcriptomes of both C. trachomatis and the host cells at 1 and 24 hours post-infection. Chlamydiae are obligate intracellular bacterial pathogens that cause a range of mammalian diseases. In humans chlamydiae are responsible for the most common sexually transmitted bacterial infections and trachoma (infectious blindness). Disease arises by adverse host inflammatory reactions that induce tissue damage & scarring. However, little is known about the mechanisms underlying these outcomes. Chlamydia are genetically intractable as replication outside of the host cell is not yet possible and there are no practical tools for routine genetic manipulation, making genome-scale approaches critical. The early timeframe of infection is poorly understood and the host transcriptional response to chlamydial infection is not well defined. Our simultaneous RNA-Seq method was applied to a simplified in vitro model of chlamydial infection. We discovered a possible chlamydial strategy for early iron acquisition, putative immune dampening effects of chlamydial infection on the host cell, and present a hypothesis for Chlamydia-induced fibrotic scarring through runaway positive feedback loops. In general, simultaneous RNA-Seq helps to reveal the complex interplay between invading bacterial pathogens and their host mammalian cells and is immediately applicable to any bacteria/host cell interaction.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080597PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851178PMC
September 2014

Kinetic and phylogenetic analysis of plant polyamine uptake transporters.

Planta 2012 Oct 19;236(4):1261-73. Epub 2012 Jun 19.

Department of Biological Sciences, Bowling Green State University, Bowling Green, OH 43403, USA.

The rice gene Polyamine Uptake Transporter1 (PUT1) was originally identified based on its homology to the polyamine uptake transporters LmPOT1 and TcPAT12 in Leishmania major and Trypanosoma cruzi, respectively. Here we show that five additional transporters from rice and Arabidopsis that cluster in the same clade as PUT1 all function as high affinity spermidine uptake transporters. Yeast expression assays of these genes confirmed that uptake of spermidine was minimally affected by 166 fold or greater concentrations of amino acids. Characterized polyamine transporters from both Arabidopsis thaliana and Oryza sativa along with the two polyamine transporters from L. major and T. cruzi were aligned and used to generate a hidden Markov model. This model was used to identify significant matches to proteins in other angiosperms, bryophytes, chlorophyta, discicristates, excavates, stramenopiles and amoebozoa. No significant matches were identified in fungal or metazoan genomes. Phylogenic analysis showed that some sequences from the haptophyte, Emiliania huxleyi, as well as sequences from oomycetes and diatoms clustered closer to sequences from plant genomes than from a homologous sequence in the red algal genome Galdieria sulphuraria, consistent with the hypothesis that these polyamine transporters were acquired by horizontal transfer from green algae. Leishmania and Trypansosoma formed a separate cluster with genes from other Discicristates and two Entamoeba species. We surmise that the genes in Entamoeba species were acquired by phagotrophy of Discicristates. In summary, phylogenetic and functional analysis has identified two clades of genes that are predictive of polyamine transport activity.
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http://dx.doi.org/10.1007/s00425-012-1668-0DOI Listing
October 2012

Draft genome sequences of the diarrheagenic Escherichia coli collection.

J Bacteriol 2012 Jun;194(11):3026-7

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.

We report the draft genome sequences of the collection referred to as the Escherichia coli DECA collection, which was assembled to contain representative isolates of the 15 most common diarrheagenic clones in humans (http://shigatox.net/new/). These genomes represent a valuable resource to the community of researchers who examine these enteric pathogens.
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http://dx.doi.org/10.1128/JB.00426-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370608PMC
June 2012

The Aspergillus Genome Database (AspGD): recent developments in comprehensive multispecies curation, comparative genomics and community resources.

Nucleic Acids Res 2012 Jan 12;40(Database issue):D653-9. Epub 2011 Nov 12.

Department of Genetics, Stanford University Medical School, Stanford, CA 94305-5120, USA.

The Aspergillus Genome Database (AspGD; http://www.aspgd.org) is a freely available, web-based resource for researchers studying fungi of the genus Aspergillus, which includes organisms of clinical, agricultural and industrial importance. AspGD curators have now completed comprehensive review of the entire published literature about Aspergillus nidulans and Aspergillus fumigatus, and this annotation is provided with streamlined, ortholog-based navigation of the multispecies information. AspGD facilitates comparative genomics by providing a full-featured genomics viewer, as well as matched and standardized sets of genomic information for the sequenced aspergilli. AspGD also provides resources to foster interaction and dissemination of community information and resources. We welcome and encourage feedback at aspergillus-curator@lists.stanford.edu.
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http://dx.doi.org/10.1093/nar/gkr875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245136PMC
January 2012

Signatures of adaptation to obligate biotrophy in the Hyaloperonospora arabidopsidis genome.

Science 2010 Dec;330(6010):1549-1551

Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA, 24061, USA.

Many oomycete and fungal plant pathogens are obligate biotrophs, which extract nutrients only from living plant tissue and cannot grow apart from their hosts. Although these pathogens cause substantial crop losses, little is known about the molecular basis or evolution of obligate biotrophy. Here, we report the genome sequence of the oomycete Hyaloperonospora arabidopsidis (Hpa), an obligate biotroph and natural pathogen of Arabidopsis thaliana. In comparison with genomes of related, hemibiotrophic Phytophthora species, the Hpa genome exhibits dramatic reductions in genes encoding (i) RXLR effectors and other secreted pathogenicity proteins, (ii) enzymes for assimilation of inorganic nitrogen and sulfur, and (iii) proteins associated with zoospore formation and motility. These attributes comprise a genomic signature of evolution toward obligate biotrophy.
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http://dx.doi.org/10.1126/science.1195203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971456PMC
December 2010

Unifying themes in microbial associations with animal and plant hosts described using the gene ontology.

Microbiol Mol Biol Rev 2010 Dec;74(4):479-503

Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Washington Street, Blacksburg, VA 24061-0477, USA.

Microbes form intimate relationships with hosts (symbioses) that range from mutualism to parasitism. Common microbial mechanisms involved in a successful host association include adhesion, entry of the microbe or its effector proteins into the host cell, mitigation of host defenses, and nutrient acquisition. Genes associated with these microbial mechanisms are known for a broad range of symbioses, revealing both divergent and convergent strategies. Effective comparisons among these symbioses, however, are hampered by inconsistent descriptive terms in the literature for functionally similar genes. Bioinformatic approaches that use homology-based tools are limited to identifying functionally similar genes based on similarities in their sequences. An effective solution to these limitations is provided by the Gene Ontology (GO), which provides a standardized language to describe gene products from all organisms. The GO comprises three ontologies that enable one to describe the molecular function(s) of gene products, the biological processes to which they contribute, and their cellular locations. Beginning in 2004, the Plant-Associated Microbe Gene Ontology (PAMGO) interest group collaborated with the GO consortium to extend the GO to accommodate terms for describing gene products associated with microbe-host interactions. Currently, over 900 terms that describe biological processes common to diverse plant- and animal-associated microbes are incorporated into the GO database. Here we review some unifying themes common to diverse host-microbe associations and illustrate how the new GO terms facilitate a standardized description of the gene products involved. We also highlight areas where new terms need to be developed, an ongoing process that should involve the whole community.
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http://dx.doi.org/10.1128/MMBR.00017-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008171PMC
December 2010

The Aspergillus Genome Database, a curated comparative genomics resource for gene, protein and sequence information for the Aspergillus research community.

Nucleic Acids Res 2010 Jan 22;38(Database issue):D420-7. Epub 2009 Sep 22.

Department of Genetics, Stanford University Medical School, Stanford, CA 94305-5120, USA.

The Aspergillus Genome Database (AspGD) is an online genomics resource for researchers studying the genetics and molecular biology of the Aspergilli. AspGD combines high-quality manual curation of the experimental scientific literature examining the genetics and molecular biology of Aspergilli, cutting-edge comparative genomics approaches to iteratively refine and improve structural gene annotations across multiple Aspergillus species, and web-based research tools for accessing and exploring the data. All of these data are freely available at http://www.aspgd.org. We welcome feedback from users and the research community at aspergillus-curator@genome.stanford.edu.
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http://dx.doi.org/10.1093/nar/gkp751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808984PMC
January 2010

Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans.

Authors:
Brian J Haas Sophien Kamoun Michael C Zody Rays H Y Jiang Robert E Handsaker Liliana M Cano Manfred Grabherr Chinnappa D Kodira Sylvain Raffaele Trudy Torto-Alalibo Tolga O Bozkurt Audrey M V Ah-Fong Lucia Alvarado Vicky L Anderson Miles R Armstrong Anna Avrova Laura Baxter Jim Beynon Petra C Boevink Stephanie R Bollmann Jorunn I B Bos Vincent Bulone Guohong Cai Cahid Cakir James C Carrington Megan Chawner Lucio Conti Stefano Costanzo Richard Ewan Noah Fahlgren Michael A Fischbach Johanna Fugelstad Eleanor M Gilroy Sante Gnerre Pamela J Green Laura J Grenville-Briggs John Griffith Niklaus J Grünwald Karolyn Horn Neil R Horner Chia-Hui Hu Edgar Huitema Dong-Hoon Jeong Alexandra M E Jones Jonathan D G Jones Richard W Jones Elinor K Karlsson Sridhara G Kunjeti Kurt Lamour Zhenyu Liu Lijun Ma Daniel Maclean Marcus C Chibucos Hayes McDonald Jessica McWalters Harold J G Meijer William Morgan Paul F Morris Carol A Munro Keith O'Neill Manuel Ospina-Giraldo Andrés Pinzón Leighton Pritchard Bernard Ramsahoye Qinghu Ren Silvia Restrepo Sourav Roy Ari Sadanandom Alon Savidor Sebastian Schornack David C Schwartz Ulrike D Schumann Ben Schwessinger Lauren Seyer Ted Sharpe Cristina Silvar Jing Song David J Studholme Sean Sykes Marco Thines Peter J I van de Vondervoort Vipaporn Phuntumart Stephan Wawra Rob Weide Joe Win Carolyn Young Shiguo Zhou William Fry Blake C Meyers Pieter van West Jean Ristaino Francine Govers Paul R J Birch Stephen C Whisson Howard S Judelson Chad Nusbaum

Nature 2009 Sep 9;461(7262):393-8. Epub 2009 Sep 9.

Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA.

Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars. Here we report the sequence of the P. infestans genome, which at approximately 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for approximately 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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http://dx.doi.org/10.1038/nature08358DOI Listing
September 2009

Describing commonalities in microbial effector delivery using the Gene Ontology.

Trends Microbiol 2009 Jul 1;17(7):312-9. Epub 2009 Jul 1.

Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.

Myriad symbiotic microbes, ranging from mutualistic through to pathogenic, deliver 'effector' molecules into the cytoplasm or cellular milieu of their hosts to facilitate colonization. Among ecologically and evolutionarily diverse taxa, analogous processes and structures exist to facilitate effector delivery. These include syringe-like injection (bacteria and nematodes), common host-targeting signals (oomycetes and protozoans) and specialized intercellular structures (fungi and oomycetes). Here, we briefly introduce readers to the Gene Ontology (GO), a controlled vocabulary to facilitate comparative genomics of diverse taxa. We also summarize and compare selected mechanisms of effector delivery from various organisms and show how careful annotation of gene products with GO can reveal underlying similarities among diverse taxa.
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http://dx.doi.org/10.1016/j.tim.2009.05.001DOI Listing
July 2009

Common processes in pathogenesis by fungal and oomycete plant pathogens, described with Gene Ontology terms.

BMC Microbiol 2009 Feb 19;9 Suppl 1:S7. Epub 2009 Feb 19.

Center for Integrated Fungal Research, North Carolina State University, Raleigh, NC 27695, USA.

Plant diseases caused by fungi and oomycetes result in significant economic losses every year. Although phylogenetically distant, the infection processes by these organisms share many common features. These include dispersal of an infectious particle, host adhesion, recognition, penetration, invasive growth, and lesion development. Previously, many of these common processes did not have corresponding Gene Ontology (GO) terms. For example, no GO terms existed to describe processes related to the appressorium, an important structure for infection by many fungi and oomycetes. In this mini-review, we identify common features of the pathogenic processes of fungi and oomycetes and create a pathogenesis model using 256 newly developed and 38 extant GO terms, with an emphasis on the appressorium and signal transduction. This set of standardized GO terms provides a solid base to further compare and contrast the molecular underpinnings of fungal and oomycete pathogenesis.
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http://dx.doi.org/10.1186/1471-2180-9-S1-S7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654667PMC
February 2009

Common themes in nutrient acquisition by plant symbiotic microbes, described by the Gene Ontology.

BMC Microbiol 2009 Feb 19;9 Suppl 1:S6. Epub 2009 Feb 19.

Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.

A critical function for symbionts is the acquisition of nutrients from their host. Relationships between hosts and symbionts range from biotrophic mutualism to necrotrophic parasitism, with a corresponding range of structures to facilitate nutrient flow between host and symbiont. Here, we review common themes among the nutrient acquisition strategies of a range of plant symbiotic microorganisms, including mutualistic symbionts, biotrophic pathogens that feed from living tissue, necrotrophic pathogens that kill host tissue, and hemibiotrophic pathogens that switch from biotrophy to necrotrophy. We show how Gene Ontology (GO) terms developed by the Plant-Associated Microbe Gene Ontology (PAMGO) Consortium can be used for describing commonalities in nutrient acquisition among diverse plant symbionts. Where appropriate, parallels found among animal symbionts are also highlighted.
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http://dx.doi.org/10.1186/1471-2180-9-S1-S6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654666PMC
February 2009

Programmed cell death in host-symbiont associations, viewed through the Gene Ontology.

BMC Microbiol 2009 Feb 19;9 Suppl 1:S5. Epub 2009 Feb 19.

Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.

Manipulation of programmed cell death (PCD) is central to many host microbe interactions. Both plant and animal cells use PCD as a powerful weapon against biotrophic pathogens, including viruses, which draw their nutrition from living tissue. Thus, diverse biotrophic pathogens have evolved many mechanisms to suppress programmed cell death, and mutualistic and commensal microbes may employ similar mechanisms. Necrotrophic pathogens derive their nutrition from dead tissue, and many produce toxins specifically to trigger programmed cell death in their hosts. Hemibiotrophic pathogens manipulate PCD in a most exquisite way, suppressing PCD during the biotrophic phase and stimulating it during the necrotrophic phase. This mini-review will summarize the mechanisms that have evolved in diverse microbes and hosts for controlling PCD and the Gene Ontology terms developed by the Plant-Associated Microbe Gene Ontology (PAMGO) Consortium for describing those mechanisms.
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http://dx.doi.org/10.1186/1471-2180-9-S1-S5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654665PMC
February 2009