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ABSTRACT: During evolution, gene repatterning across eukaryotic genomes is not uniform. Some genomic regions exhibit a gene organization conserved phylogenetically, while others are recurrently involved in chromosomal rearrangement, resulting in breakpoint reuse. Both gene order conservation and breakpoint reuse can result from the existence of functional constraints on where chromosomal breakpoints occur or from the existence of regions that are susceptible to breakage. The balance between these two mechanisms is still poorly understood. Drosophila species have very dynamic genomes and, therefore, can be very informative. We compared the gene organization of the main five chromosomal elements (Muller's elements A-E) of nine Drosophila species. Under a parsimonious evolutionary scenario, we estimate that 6116 breakpoints differentiate the gene orders of the species and that breakpoint reuse is associated with approximately 80% of the orthologous landmarks. The comparison of the observed patterns of change in gene organization with those predicted under different simulated modes of evolution shows that fragile regions alone can explain the observed key patterns of Muller's element A (X chromosome) more often than for any other Muller's element. High levels of fragility plus constraints operating on approximately 15% of the genome are sufficient to explain the observed patterns of change and conservation across species. The orthologous landmarks more likely to be under constraint exhibit both a remarkable internal functional heterogeneity and a lack of common functional themes with the exception of the presence of highly conserved noncoding elements. Fragile regions rather than functional constraints have been the main determinant of the evolution of the Drosophila chromosomes.
Genome Research 08/2010; 20(8):1084-96. · 13.61 Impact Factor
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ABSTRACT: Phenotype ontologies are typically constructed to serve the needs of a particular community, such as annotation of genotype-phenotype associations in mouse or human. Here we demonstrate how these ontologies can be improved through assignment of logical definitions using a core ontology of phenotypic qualities and multiple additional ontologies from the Open Biological Ontologies library. We also show how these logical definitions can be used for data integration when combined with a unified multi-species anatomy ontology.
Genome biology 01/2010; 11(1):R2. · 6.63 Impact Factor
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ABSTRACT: Scientists and clinicians who study genetic alterations and disease have traditionally described phenotypes in natural language. The considerable variation in these free-text descriptions has posed a hindrance to the important task of identifying candidate genes and models for human diseases and indicates the need for a computationally tractable method to mine data resources for mutant phenotypes. In this study, we tested the hypothesis that ontological annotation of disease phenotypes will facilitate the discovery of new genotype-phenotype relationships within and across species. To describe phenotypes using ontologies, we used an Entity-Quality (EQ) methodology, wherein the affected entity (E) and how it is affected (Q) are recorded using terms from a variety of ontologies. Using this EQ method, we annotated the phenotypes of 11 gene-linked human diseases described in Online Mendelian Inheritance in Man (OMIM). These human annotations were loaded into our Ontology-Based Database (OBD) along with other ontology-based phenotype descriptions of mutants from various model organism databases. Phenotypes recorded with this EQ method can be computationally compared based on the hierarchy of terms in the ontologies and the frequency of annotation. We utilized four similarity metrics to compare phenotypes and developed an ontology of homologous and analogous anatomical structures to compare phenotypes between species. Using these tools, we demonstrate that we can identify, through the similarity of the recorded phenotypes, other alleles of the same gene, other members of a signaling pathway, and orthologous genes and pathway members across species. We conclude that EQ-based annotation of phenotypes, in conjunction with a cross-species ontology, and a variety of similarity metrics can identify biologically meaningful similarities between genes by comparing phenotypes alone. This annotation and search method provides a novel and efficient means to identify gene candidates and animal models of human disease, which may shorten the lengthy path to identification and understanding of the genetic basis of human disease.
PLoS Biology 11/2009; 7(11):e1000247. · 11.45 Impact Factor
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Susan Tweedie, Michael Ashburner,
Kathleen Falls,
Paul Leyland,
Peter McQuilton,
Steven Marygold,
Gillian H. Millburn,
David Osumi-Sutherland,
Andrew Schroeder,
Ruth Seal,
Haiyan Zhang
Nucleic Acids Research. 01/2009; 37:555-559.
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ABSTRACT: This paper describes an approach to providing computer-interpretable logical definitions for the terms of the Human Phenotype Ontology (HPO) using PATO, the ontology of phenotypic qualities, to link terms of the HPO to the anatomic and other entities that are affected by abnormal phenotypic qualities. This approach will allow improved computerized reasoning as well as a facility to compare phenotypes between different species. The PATO mapping will also provide direct links from phenotypic abnormalities and underlying anatomic structures encoded using the Foundational Model of Anatomy, which will be a valuable resource for computational investigations of the links between anatomical components and concepts representing diseases with abnormal phenotypes and associated genes.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:7069-72.
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ABSTRACT: Wolbachia are vertically transmitted, obligatory intracellular bacteria that infect a great number of species of arthropods and nematodes. In insects, they are mainly known for disrupting the reproductive biology of their hosts in order to increase their transmission through the female germline. In Drosophila melanogaster, however, a strong and consistent effect of Wolbachia infection has not been found. Here we report that a bacterial infection renders D. melanogaster more resistant to Drosophila C virus, reducing the load of viruses in infected flies. We identify these resistance-inducing bacteria as Wolbachia. Furthermore, we show that Wolbachia also increases resistance of Drosophila to two other RNA virus infections (Nora virus and Flock House virus) but not to a DNA virus infection (Insect Iridescent Virus 6). These results identify a new major factor regulating D. melanogaster resistance to infection by RNA viruses and contribute to the idea that the response of a host to a particular pathogen also depends on its interactions with other microorganisms. This is also, to our knowledge, the first report of a strong beneficial effect of Wolbachia infection in D. melanogaster. The induced resistance to natural viral pathogens may explain Wolbachia prevalence in natural populations and represents a novel Wolbachia-host interaction.
PLoS Biology 01/2009; 6(12):e2. · 11.45 Impact Factor
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Susan Tweedie, Michael Ashburner,
Kathleen Falls,
Paul Leyland,
Peter McQuilton,
Steven Marygold,
Gillian Millburn,
David Osumi-Sutherland,
Andrew Schroeder,
Ruth Seal,
Haiyan Zhang
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ABSTRACT: FlyBase (http://flybase.org) is a database of Drosophila genetic and genomic information. Gene Ontology (GO) terms are used to describe three attributes of wild-type gene products: their molecular function, the biological processes in which they play a role, and their subcellular location. This article describes recent changes to the FlyBase GO annotation strategy that are improving the quality of the GO annotation data. Many of these changes stem from our participation in the GO Reference Genome Annotation Project--a multi-database collaboration producing comprehensive GO annotation sets for 12 diverse species.
Nucleic Acids Research 11/2008; 37(Database issue):D555-9. · 8.03 Impact Factor
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Chris F Taylor,
Dawn Field,
Susanna-Assunta Sansone,
Jan Aerts,
Rolf Apweiler, Michael Ashburner,
Catherine A Ball,
Pierre-Alain Binz,
Molly Bogue,
Tim Booth, [......],
Richard H Scheuermann,
Daniel Schober,
Barry Smith,
Jason Snape,
Christian J Stoeckert,
Keith Tipton,
Peter Sterk,
Andreas Untergasser,
Jo Vandesompele,
Stefan Wiemann
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ABSTRACT: The Minimum Information for Biological and Biomedical Investigations (MIBBI) project provides a resource for those exploring the range of extant minimum information checklists and fosters coordinated development of such checklists. European Union Framework VI project META- PHOR (Food-ST-2006-03622)
Nature Biotechnology 09/2008; 26(8):889-96. · 29.50 Impact Factor
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Dawn Field,
George Garrity,
Tanya Gray,
Norman Morrison,
Jeremy Selengut,
Peter Sterk,
Tatiana Tatusova,
Nicholas Thomson,
Michael J Allen,
Samuel V Angiuoli, [......],
Yoshio Tateno,
Adrian Tett,
Sarah Turner,
David Ussery,
Bob Vaughan,
Naomi Ward,
Trish Whetzel,
Ingio San Gil,
Gareth Wilson,
Anil Wipat
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ABSTRACT: With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the 'transparency' of the information contained in existing genomic databases.
Nature Biotechnology 06/2008; 26(5):541-7. · 29.50 Impact Factor
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Barend Mons, Michael Ashburner,
Christine Chichester,
Erik van Mulligen,
Marc Weeber,
Johan den Dunnen,
Gert-Jan van Ommen,
Mark Musen,
Matthew Cockerill,
Henning Hermjakob, [......],
Suzanna Lewis,
Alfred Berkeley,
William Melton,
Nickolas Barris,
Jimmy Wales,
Gerard Meijssen,
Erik Moeller,
Peter Jan Roes,
Katy Borner,
Amos Bairoch
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ABSTRACT: WikiProteins enables community annotation in a Wiki-based system. Extracts of major data sources have been fused into an editable environment that links out to the original sources. Data from community edits create automatic copies of the original data. Semantic technology captures concepts co-occurring in one sentence and thus potential factual statements. In addition, indirect associations between concepts have been calculated. We call on a 'million minds' to annotate a 'million concepts' and to collect facts from the literature with the reward of collaborative knowledge discovery. The system is available for beta testing at http://www.wikiprofessional.org.
Genome biology 02/2008; 9(5):R89. · 6.63 Impact Factor
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Ontologies and Text Mining for Life Sciences: Current Status and Future Perspectives, 24.03. - 28.03.2008; 01/2008
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Michael Ashburner
Genetics 12/2007; 177(3):1263-8. · 4.01 Impact Factor
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Barry Smith, Michael Ashburner,
Cornelius Rosse,
Jonathan Bard,
William Bug,
Werner Ceusters,
Louis J Goldberg,
Karen Eilbeck,
Amelia Ireland,
Christopher J Mungall,
Neocles Leontis,
Philippe Rocca-Serra,
Alan Ruttenberg,
Susanna-Assunta Sansone,
Richard H Scheuermann,
Nigam Shah,
Patricia L Whetzel,
Suzanna Lewis
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ABSTRACT: The value of any kind of data is greatly enhanced when it exists in a form that allows it to be integrated with other data. One approach to integration is through the annotation of multiple bodies of data using common controlled vocabularies or 'ontologies'. Unfortunately, the very success of this approach has led to a proliferation of ontologies, which itself creates obstacles to integration. The Open Biomedical Ontologies (OBO) consortium is pursuing a strategy to overcome this problem. Existing OBO ontologies, including the Gene Ontology, are undergoing coordinated reform, and new ontologies are being created on the basis of an evolving set of shared principles governing ontology development. The result is an expanding family of ontologies designed to be interoperable and logically well formed and to incorporate accurate representations of biological reality. We describe this OBO Foundry initiative and provide guidelines for those who might wish to become involved.
Nature Biotechnology 12/2007; 25(11):1251-5. · 23.27 Impact Factor
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Edward Ryder, Michael Ashburner,
Rosa Bautista-Llacer,
Jenny Drummond,
Jane Webster,
Glynnis Johnson,
Terri Morley,
Yuk Sang Chan,
Fiona Blows,
Darin Coulson, [......],
Gert Pflugfelder,
Christian Dorner,
Bernard Mechler,
Heide Schenkel,
Joachim Marhold,
Florenci Serras,
Montserrat Corominas,
Adrià Punset,
John Roote,
Steven Russell
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ABSTRACT: We describe a second-generation deficiency kit for Drosophila melanogaster composed of molecularly mapped deletions on an isogenic background, covering approximately 77% of the Release 5.1 genome. Using a previously reported collection of FRT-bearing P-element insertions, we have generated 655 new deletions and verified a set of 209 deletion-bearing fly stocks. In addition to deletions, we demonstrate how the P elements may also be used to generate a set of custom inversions and duplications, particularly useful for balancing difficult regions of the genome carrying haplo-insufficient loci. We describe a simple computational resource that facilitates selection of appropriate elements for generating custom deletions. Finally, we provide a computational resource that facilitates selection of other mapped FRT-bearing elements that, when combined with the DrosDel collection, can theoretically generate over half a million precisely mapped deletions.
Genetics 10/2007; 177(1):615-29. · 4.01 Impact Factor
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ABSTRACT: Understanding the developmental and genetic underpinnings of particular evolutionary changes has been hindered by inadequate databases of evolutionary anatomy and by the lack of a computational approach to identify underlying candidate genes and regulators. By contrast, model organism studies have been enhanced by ontologies shared among genomic databases. Here, we suggest that evolutionary and genomics databases can be developed to exchange and use information through shared phenotype and anatomy ontologies. This would facilitate computing on evolutionary questions pertaining to the genetic basis of evolutionary change, the genetic and developmental bases of correlated characters and independent evolution, biomedical parallels to evolutionary change, and the ecological and paleontological correlates of particular types of change in genes, gene networks and developmental pathways.
Trends in Ecology & Evolution 08/2007; 22(7):345-50. · 15.75 Impact Factor
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ABSTRACT: That closely related species often differ by chromosomal inversions was discovered by Sturtevant and Plunkett in 1926. Our knowledge of how these inversions originate is still very limited, although a prevailing view is that they are facilitated by ectopic recombination events between inverted repetitive sequences. The availability of genome sequences of related species now allows us to study in detail the mechanisms that generate interspecific inversions. We have analyzed the breakpoint regions of the 29 inversions that differentiate the chromosomes of Drosophila melanogaster and two closely related species, D. simulans and D. yakuba, and reconstructed the molecular events that underlie their origin. Experimental and computational analysis revealed that the breakpoint regions of 59% of the inversions (17/29) are associated with inverted duplications of genes or other nonrepetitive sequences. In only two cases do we find evidence for inverted repetitive sequences in inversion breakpoints. We propose that the presence of inverted duplications associated with inversion breakpoint regions is the result of staggered breaks, either isochromatid or chromatid, and that this, rather than ectopic exchange between inverted repetitive sequences, is the prevalent mechanism for the generation of inversions in the melanogaster species group. Outgroup analysis also revealed evidence for widespread breakpoint recycling. Lastly, we have found that expression domains in D. melanogaster may be disrupted in D. yakuba, bringing into question their potential adaptive significance.
PLoS Biology 07/2007; 5(6):e152. · 11.45 Impact Factor
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Steven J Marygold,
John Roote,
Gunter Reuter,
Andrew Lambertsson, Michael Ashburner,
Gillian H Millburn,
Paul M Harrison,
Zhan Yu,
Naoya Kenmochi,
Thomas C Kaufman,
Sally J Leevers,
Kevin R Cook
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ABSTRACT: Mutations in genes encoding ribosomal proteins (RPs) have been shown to cause an array of cellular and developmental defects in a variety of organisms. In Drosophila melanogaster, disruption of RP genes can result in the 'Minute' syndrome of dominant, haploinsufficient phenotypes, which include prolonged development, short and thin bristles, and poor fertility and viability. While more than 50 Minute loci have been defined genetically, only 15 have so far been characterized molecularly and shown to correspond to RP genes.
We combined bioinformatic and genetic approaches to conduct a systematic analysis of the relationship between RP genes and Minute loci. First, we identified 88 genes encoding 79 different cytoplasmic RPs (CRPs) and 75 genes encoding distinct mitochondrial RPs (MRPs). Interestingly, nine CRP genes are present as duplicates and, while all appear to be functional, one member of each gene pair has relatively limited expression. Next, we defined 65 discrete Minute loci by genetic criteria. Of these, 64 correspond to, or very likely correspond to, CRP genes; the single non-CRP-encoding Minute gene encodes a translation initiation factor subunit. Significantly, MRP genes and more than 20 CRP genes do not correspond to Minute loci.
This work answers a longstanding question about the molecular nature of Minute loci and suggests that Minute phenotypes arise from suboptimal protein synthesis resulting from reduced levels of cytoribosomes. Furthermore, by identifying the majority of haplolethal and haplosterile loci at the molecular level, our data will directly benefit efforts to attain complete deletion coverage of the D. melanogaster genome.
Genome biology 02/2007; 8(10):R216. · 6.63 Impact Factor
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Rachel Lyne,
Richard Smith,
Kim Rutherford,
Matthew Wakeling,
Andrew Varley,
Francois Guillier,
Hilde Janssens,
Wenyan Ji,
Peter Mclaren,
Philip North,
Debashis Rana,
Tom Riley,
Julie Sullivan,
Xavier Watkins,
Mark Woodbridge,
Kathryn Lilley,
Steve Russell, Michael Ashburner,
Kenji Mizuguchi,
Gos Micklem
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ABSTRACT: FlyMine is a data warehouse that addresses one of the important challenges of modern biology: how to integrate and make use of the diversity and volume of current biological data. Its main focus is genomic and proteomics data for Drosophila and other insects. It provides web access to integrated data at a number of different levels, from simple browsing to construction of complex queries, which can be executed on either single items or lists.
Genome biology 02/2007; 8(7):R129. · 6.63 Impact Factor
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ABSTRACT: INTRODUCTIONSince its introduction to experimental biology more than 90 years ago, Drosophila melanogaster has proved to be an easily cultured and robust laboratory animal. Although culture techniques and the ways in which flies are handled have changed over the years, if he were to enter a fly room today, T.H. Morgan would clearly recognize what is being done, and why. This article provides the basic methods for the laboratory culture of D. melanogaster. The intelligent culture of Drosophila requires a basic understanding of the life cycle of this fly. For this reason, we begin by describing the life cycle of Drosophila and then present information for setting up a fly laboratory.
CSH protocols. 01/2007; 2007:pdb.ip34.
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ABSTRACT: INTRODUCTIONThis article provides a general introduction to keeping Drosophila stocks, making and scoring crosses, mutagenesis, and controlling diseases in the laboratory.
CSH protocols. 01/2007; 2007:pdb.ip35.
