ABSTRACT
[This corrects the article DOI: 10.1371/journal.pbio.1000281.].
ABSTRACT
Drosophila, like other invertebrates and plants, relies mainly on RNA interference for its defense against viruses. In flies, viral infection also triggers the expression of many genes. One of the genes induced, Vago, encodes a 18-kilodalton cysteine-rich polypeptide. Here we provide genetic evidence that the Vago gene product controlled viral load in the fat body after infection with drosophila C virus. Induction of Vago was dependent on the helicase Dicer-2. Dicer-2 belongs to the same DExD/H-box helicase family as do the RIG-I-like receptors, which sense viral infection and mediate interferon induction in mammals. We propose that this family represents an evolutionary conserved set of sensors that detect viral nucleic acids and direct antiviral responses.
Subject(s)
Drosophila Proteins/immunology , Drosophila/immunology , Drosophila/virology , RNA Helicases/immunology , Animals , Animals, Genetically Modified , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Electrophoresis, Polyacrylamide Gel , Fat Body/immunology , Fat Body/virology , Gene Expression Regulation/immunology , Humans , Phylogeny , RNA Helicases/genetics , RNA Helicases/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Ribonuclease III , Sequence Homology, Amino Acid , Transcription, Genetic , Virus Diseases/immunologyABSTRACT
SUMMARY: Rapid technological advances have led to an explosion of biomedical data in recent years. The pace of change has inspired new collaborative approaches for sharing materials and resources to help train life scientists both in the use of cutting-edge bioinformatics tools and databases and in how to analyse and interpret large datasets. A prototype platform for sharing such training resources was recently created by the Bioinformatics Training Network (BTN). Building on this work, we have created a centralized portal for sharing training materials and courses, including a catalogue of trainers and course organizers, and an announcement service for training events. For course organizers, the portal provides opportunities to promote their training events; for trainers, the portal offers an environment for sharing materials, for gaining visibility for their work and promoting their skills; for trainees, it offers a convenient one-stop shop for finding suitable training resources and identifying relevant training events and activities locally and worldwide. AVAILABILITY AND IMPLEMENTATION: http://mygoblet.org/training-portal.
Subject(s)
Computational Biology/education , Curriculum , Database Management Systems , Research Personnel/education , Teaching , Humans , Programming Languages , Software DesignABSTRACT
"Scientific community" refers to a group of people collaborating together on scientific-research-related activities who also share common goals, interests, and values. Such communities play a key role in many bioinformatics activities. Communities may be linked to a specific location or institute, or involve people working at many different institutions and locations. Education and training is typically an important component of these communities, providing a valuable context in which to develop skills and expertise, while also strengthening links and relationships within the community. Scientific communities facilitate: (i) the exchange and development of ideas and expertise; (ii) career development; (iii) coordinated funding activities; (iv) interactions and engagement with professionals from other fields; and (v) other activities beneficial to individual participants, communities, and the scientific field as a whole. It is thus beneficial at many different levels to understand the general features of successful, high-impact bioinformatics communities; how individual participants can contribute to the success of these communities; and the role of education and training within these communities. We present here a quick guide to building and maintaining a successful, high-impact bioinformatics community, along with an overview of the general benefits of participating in such communities. This article grew out of contributions made by organizers, presenters, panelists, and other participants of the ISMB/ECCB 2013 workshop "The 'How To Guide' for Establishing a Successful Bioinformatics Network" at the 21st Annual International Conference on Intelligent Systems for Molecular Biology (ISMB) and the 12th European Conference on Computational Biology (ECCB).
Subject(s)
Communication , Computational Biology/organization & administration , Humans , Internet , Social MediaABSTRACT
The eukaryotic linear motif (ELM http://elm.eu.org) resource is a hub for collecting, classifying and curating information about short linear motifs (SLiMs). For >10 years, this resource has provided the scientific community with a freely accessible guide to the biology and function of linear motifs. The current version of ELM contains â¼200 different motif classes with over 2400 experimentally validated instances manually curated from >2000 scientific publications. Furthermore, detailed information about motif-mediated interactions has been annotated and made available in standard exchange formats. Where appropriate, links are provided to resources such as switches.elm.eu.org and KEGG pathways.
Subject(s)
Amino Acid Motifs , Databases, Protein , Protein Interaction Domains and Motifs , Internet , Multiprotein Complexes/chemistryABSTRACT
The mountains of data thrusting from the new landscape of modern high-throughput biology are irrevocably changing biomedical research and creating a near-insatiable demand for training in data management and manipulation and data mining and analysis. Among life scientists, from clinicians to environmental researchers, a common theme is the need not just to use, and gain familiarity with, bioinformatics tools and resources but also to understand their underlying fundamental theoretical and practical concepts. Providing bioinformatics training to empower life scientists to handle and analyse their data efficiently, and progress their research, is a challenge across the globe. Delivering good training goes beyond traditional lectures and resource-centric demos, using interactivity, problem-solving exercises and cooperative learning to substantially enhance training quality and learning outcomes. In this context, this article discusses various pragmatic criteria for identifying training needs and learning objectives, for selecting suitable trainees and trainers, for developing and maintaining training skills and evaluating training quality. Adherence to these criteria may help not only to guide course organizers and trainers on the path towards bioinformatics training excellence but, importantly, also to improve the training experience for life scientists.
Subject(s)
Biological Science Disciplines/education , Computational Biology/education , Curriculum , Data Mining , Database Management Systems , Programming Languages , Software Design , TeachingABSTRACT
The third Heidelberg Unseminars in Bioinformatics (HUB) was held on 18th October 2012, at Heidelberg University, Germany. HUB brought together around 40 bioinformaticians from academia and industry to discuss the 'Biggest Challenges in Bioinformatics' in a 'World Café' style event.
Subject(s)
Computational Biology , Animals , Biodiversity , Genetic Speciation , Humans , Information Storage and Retrieval , Knowledge Management , Phylogeny , Precision MedicineABSTRACT
Funding bodies are increasingly recognizing the need to provide graduates and researchers with access to short intensive courses in a variety of disciplines, in order both to improve the general skills base and to provide solid foundations on which researchers may build their careers. In response to the development of 'high-throughput biology', the need for training in the field of bioinformatics, in particular, is seeing a resurgence: it has been defined as a key priority by many Institutions and research programmes and is now an important component of many grant proposals. Nevertheless, when it comes to planning and preparing to meet such training needs, tension arises between the reward structures that predominate in the scientific community which compel individuals to publish or perish, and the time that must be devoted to the design, delivery and maintenance of high-quality training materials. Conversely, there is much relevant teaching material and training expertise available worldwide that, were it properly organized, could be exploited by anyone who needs to provide training or needs to set up a new course. To do this, however, the materials would have to be centralized in a database and clearly tagged in relation to target audiences, learning objectives, etc. Ideally, they would also be peer reviewed, and easily and efficiently accessible for downloading. Here, we present the Bioinformatics Training Network (BTN), a new enterprise that has been initiated to address these needs and review it, respectively, to similar initiatives and collections.
Subject(s)
Computational Biology/education , Community Networks , Humans , Research Personnel/educationABSTRACT
SUMMARY: We present iAnn, an open source community-driven platform for dissemination of life science events, such as courses, conferences and workshops. iAnn allows automatic visualisation and integration of customised event reports. A central repository lies at the core of the platform: curators add submitted events, and these are subsequently accessed via web services. Thus, once an iAnn widget is incorporated into a website, it permanently shows timely relevant information as if it were native to the remote site. At the same time, announcements submitted to the repository are automatically disseminated to all portals that query the system. To facilitate the visualization of announcements, iAnn provides powerful filtering options and views, integrated in Google Maps and Google Calendar. All iAnn widgets are freely available. AVAILABILITY: http://iann.pro/iannviewer CONTACT: manuel.corpas@tgac.ac.uk.
Subject(s)
Biological Science Disciplines , Software , Anniversaries and Special Events , Congresses as Topic , InternetABSTRACT
Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.
Subject(s)
Amino Acid Motifs , Databases, Protein , Computer Graphics , Disease/genetics , Eukaryota , Sequence Analysis, Protein , User-Computer Interface , Viral Proteins/chemistryABSTRACT
The development of the endomembrane system was a major step in eukaryotic evolution. Membrane coats, which exhibit a unique arrangement of beta-propeller and alpha-helical repeat domains, play key roles in shaping eukaryotic membranes. Such proteins are likely to have been present in the ancestral eukaryote but cannot be detected in prokaryotes using sequence-only searches. We have used a structure-based detection protocol to search all proteomes for proteins with this domain architecture. Apart from the eukaryotes, we identified this protein architecture only in the Planctomycetes-Verrucomicrobia-Chlamydiae (PVC) bacterial superphylum, many members of which share a compartmentalized cell plan. We determined that one such protein is partly localized at the membranes of vesicles formed inside the cells in the planctomycete Gemmata obscuriglobus. Our results demonstrate similarities between bacterial and eukaryotic compartmentalization machinery, suggesting that the bacterial PVC superphylum contributed significantly to eukaryogenesis.
Subject(s)
Bacteria/genetics , Bacterial Proteins/chemistry , Membrane Proteins/chemistry , Bacteria/classification , Bacteria/cytology , Bacterial Proteins/physiology , Biological Evolution , Cell Compartmentation , Membrane Proteins/physiology , Phylogeny , Protein Structure, Tertiary , Proteome , Sequence Analysis, ProteinABSTRACT
Ionotropic glutamate receptors (iGluRs) are a highly conserved family of ligand-gated ion channels present in animals, plants, and bacteria, which are best characterized for their roles in synaptic communication in vertebrate nervous systems. A variant subfamily of iGluRs, the Ionotropic Receptors (IRs), was recently identified as a new class of olfactory receptors in the fruit fly, Drosophila melanogaster, hinting at a broader function of this ion channel family in detection of environmental, as well as intercellular, chemical signals. Here, we investigate the origin and evolution of IRs by comprehensive evolutionary genomics and in situ expression analysis. In marked contrast to the insect-specific Odorant Receptor family, we show that IRs are expressed in olfactory organs across Protostomia--a major branch of the animal kingdom that encompasses arthropods, nematodes, and molluscs--indicating that they represent an ancestral protostome chemosensory receptor family. Two subfamilies of IRs are distinguished: conserved "antennal IRs," which likely define the first olfactory receptor family of insects, and species-specific "divergent IRs," which are expressed in peripheral and internal gustatory neurons, implicating this family in taste and food assessment. Comparative analysis of drosophilid IRs reveals the selective forces that have shaped the repertoires in flies with distinct chemosensory preferences. Examination of IR gene structure and genomic distribution suggests both non-allelic homologous recombination and retroposition contributed to the expansion of this multigene family. Together, these findings lay a foundation for functional analysis of these receptors in both neurobiological and evolutionary studies. Furthermore, this work identifies novel targets for manipulating chemosensory-driven behaviours of agricultural pests and disease vectors.
Subject(s)
Evolution, Molecular , Insect Proteins/genetics , Insecta/genetics , Receptors, Ionotropic Glutamate/genetics , Animals , Drosophila/genetics , Drosophila/metabolism , Insect Proteins/metabolism , Insecta/classification , Insecta/physiology , Invertebrates/classification , Invertebrates/genetics , Invertebrates/physiology , Molecular Sequence Data , Multigene Family , Phylogeny , Receptors, Ionotropic Glutamate/metabolism , Receptors, Odorant/genetics , Receptors, Odorant/metabolism , Smell , TasteABSTRACT
As bioinformatics becomes increasingly central to research in the molecular life sciences, the need to train non-bioinformaticians to make the most of bioinformatics resources is growing. Here, we review the key challenges and pitfalls to providing effective training for users of bioinformatics services, and discuss successful training strategies shared by a diverse set of bioinformatics trainers. We also identify steps that trainers in bioinformatics could take together to advance the state of the art in current training practices. The ideas presented in this article derive from the first Trainer Networking Session held under the auspices of the EU-funded SLING Integrating Activity, which took place in November 2009.
Subject(s)
Computational Biology/education , Research/education , Teaching/methodsABSTRACT
Melanization is an innate immune response in arthropods that encapsulates and kills invading pathogens. One of its rate-limiting steps is the activation of prophenoloxidase (PPO), which is controlled by an extracellular proteinase cascade and serpin inhibitors. The molecular composition of this system is largely unknown in mosquitoes with the exception of serpin-2 (SRPN2), which was previously identified as a key negative regulator of melanization. Using reverse genetic and biochemical techniques, we identified the Anopheles gambiae clip-serine proteinase CLIPB9 as a PPO-activating proteinase, which is inhibited by SRPN2. Double knockdown of SRPN2 and CLIPB9 reversed the pleiotrophic phenotype induced by SRPN2 silencing. This study identifies the first inhibitory serpin-serine proteinase pair in mosquitoes and defines a regulatory unit of melanization. Additionally, the interaction of CLIPB9 and SRPN2 affects the life span of adult female mosquitoes and therefore constitutes a well-defined potential molecular target for novel late-life acting insecticides.
Subject(s)
Anopheles/physiology , Longevity , Melanins/metabolism , Serpins/physiology , Animals , Anopheles/classification , Anopheles/immunology , Blotting, Western , Female , Immunity, Innate , Mass Spectrometry , Phylogeny , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Serine Proteases/metabolism , Serpins/geneticsABSTRACT
Linear motifs are short segments of multidomain proteins that provide regulatory functions independently of protein tertiary structure. Much of intracellular signalling passes through protein modifications at linear motifs. Many thousands of linear motif instances, most notably phosphorylation sites, have now been reported. Although clearly very abundant, linear motifs are difficult to predict de novo in protein sequences due to the difficulty of obtaining robust statistical assessments. The ELM resource at http://elm.eu.org/ provides an expanding knowledge base, currently covering 146 known motifs, with annotation that includes >1300 experimentally reported instances. ELM is also an exploratory tool for suggesting new candidates of known linear motifs in proteins of interest. Information about protein domains, protein structure and native disorder, cellular and taxonomic contexts is used to reduce or deprecate false positive matches. Results are graphically displayed in a 'Bar Code' format, which also displays known instances from homologous proteins through a novel 'Instance Mapper' protocol based on PHI-BLAST. ELM server output provides links to the ELM annotation as well as to a number of remote resources. Using the links, researchers can explore the motifs, proteins, complex structures and associated literature to evaluate whether candidate motifs might be worth experimental investigation.
Subject(s)
Amino Acid Motifs/genetics , Computational Biology/methods , Databases, Genetic , Databases, Nucleic Acid , Eukaryotic Cells/chemistry , Amino Acid Sequence , Animals , Computational Biology/trends , Databases, Protein , Humans , Information Storage and Retrieval/methods , Internet , Molecular Sequence Data , Protein Structure, Tertiary , Sequence Homology, Amino Acid , SoftwareABSTRACT
There is a clear need to develop novel tools to help improve our understanding of stem cell biology, and potentially also the utility of stem cells in regenerative medicine. We report the cloning, functional, and bioinformatic characterization of a novel stem cell marker in the zebrafish retina, drCol 15a1b. The expression pattern of drCol 15a1b is restricted to stem cell niches located in the central nervous system, whereas other collagen XVs are associated with muscle and endothelial tissues. Knocking down drCol 15a1b expression causes smaller eyes, ear defects, and brain edema. Microscopic analysis reveals enhanced proliferation in the morphant eye, with many mitotic nuclei located in the central retina, together with a delayed differentiation of the mature retinal cell types. Besides, several markers known to be expressed in the ciliary marginal zone display broader expression areas in morpholino-injected embryos, suggesting an anomalous diffusion of signaling effectors from the sonic hedgehog and notch pathways. These results indicate that drCol 15a1b is a novel stem cell marker in the central nervous system that has a key role in homing stem cells into specialized niches in the adult organism. Moreover, mutations in the hCol 18a1 gene are responsible for the Knobloch syndrome, which affects brain and retinal structures, suggesting that drCol 15a1b may function similarly to mammalian Col 18a1. Thus, our results shed new light on the signaling pathways that underlie the maintenance of stem cells in the adult organism while helping us to understand the role of extracellular matrix proteins in modulating the signals that determine stem cell differentiation, cell cycle exit and apoptosis.
Subject(s)
Retina/metabolism , Stem Cell Niche/metabolism , Zebrafish Proteins/metabolism , Animals , Collagen/classification , Collagen/genetics , Collagen/metabolism , Immunohistochemistry , In Situ Hybridization , Phylogeny , Polymerase Chain Reaction , Retina/embryology , Zebrafish , Zebrafish Proteins/classification , Zebrafish Proteins/geneticsABSTRACT
Nascent mRNAs produced by transcription in the nucleus are subsequently processed and packaged into mRNA ribonucleoprotein particles (messenger ribonucleoproteins (mRNPs)) before export to the cytoplasm. Here, we have used the poly(A)-binding protein Nab2 to isolate mRNPs from yeast under conditions that preserve mRNA integrity. Upon Nab2-tandem affinity purification, several mRNA export factors were co-enriched (Yra1, Mex67, THO-TREX) that were present in mRNPs of different size and mRNA length. High-throughput sequencing of the co-precipitated RNAs indicated that Nab2 is associated with the bulk of yeast transcripts with no specificity for different mRNA classes. Electron microscopy revealed that many of the mRNPs have a characteristic elongated structure. Our data suggest that mRNPs, although associated with different mRNAs, have a unifying core structure.