WormBase 2016: expanding to enable helminth genomic research.

WormBase (www.wormbase.org) is a central repository for research data on the biology, genetics and genomics of Caenorhabditis elegans and other nematodes. The project has evolved from its original remit to collect and integrate all data for a single species, and now extends to numerous nematodes, ranging from evolutionary comparators of C. elegans to parasitic species that threaten plant, animal and human health. Research activity using C. elegans as a model system is as vibrant as ever, and we have created new tools for community curation in response to the ever-increasing volume and complexity of data. To better allow users to navigate their way through these data, we have made a number of improvements to our main website, including new tools for browsing genomic features and ontology annotations. Finally, we have developed a new portal for parasitic worm genomes. WormBase ParaSite (parasite.wormbase.org) contains all publicly available nematode and platyhelminth annotated genome sequences, and is designed specifically to support helminth genomic research.

A method for increasing expressivity of Gene Ontology annotations using a compositional approach.

BACKGROUND: The Gene Ontology project integrates data about the function of gene products across a diverse range of organisms, allowing the transfer of knowledge from model organisms to humans, and enabling computational analyses for interpretation of high-throughput experimental and clinical data. The core data structure is the annotation, an association between a gene product and a term from one of the three ontologies comprising the GO. Historically, it has not been possible to provide additional information about the context of a GO term, such as the target gene or the location of a molecular function. This has limited the specificity of knowledge that can be expressed by GO annotations. RESULTS: The GO Consortium has introduced annotation extensions that enable manually curated GO annotations to capture additional contextual details. Extensions represent effector-target relationships such as localization dependencies, substrates of protein modifiers and regulation targets of signaling pathways and transcription factors as well as spatial and temporal aspects of processes such as cell or tissue type or developmental stage. We describe the content and structure of annotation extensions, provide examples, and summarize the current usage of annotation extensions. CONCLUSIONS: The additional contextual information captured by annotation extensions improves the utility of functional annotation by representing dependencies between annotations to terms in the different ontologies of GO, external ontologies, or an organism's gene products. These enhanced annotations can also support sophisticated queries and reasoning, and will provide curated, directional links between many gene products to support pathway and network reconstruction.

Dovetailing biology and chemistry: integrating the Gene Ontology with the ChEBI chemical ontology.

BACKGROUND: The Gene Ontology (GO) facilitates the description of the action of gene products in a biological context. Many GO terms refer to chemical entities that participate in biological processes. To facilitate accurate and consistent systems-wide biological representation, it is necessary to integrate the chemical view of these entities with the biological view of GO functions and processes. We describe a collaborative effort between the GO and the Chemical Entities of Biological Interest (ChEBI) ontology developers to ensure that the representation of chemicals in the GO is both internally consistent and in alignment with the chemical expertise captured in ChEBI. RESULTS: We have examined and integrated the ChEBI structural hierarchy into the GO resource through computationally-assisted manual curation of both GO and ChEBI. Our work has resulted in the creation of computable definitions of GO terms that contain fully defined semantic relationships to corresponding chemical terms in ChEBI. CONCLUSIONS: The set of logical definitions using both the GO and ChEBI has already been used to automate aspects of GO development and has the potential to allow the integration of data across the domains of biology and chemistry. These logical definitions are available as an extended version of the ontology from http://purl.obolibrary.org/obo/go/extensions/go-plus.owl.

An extension of the BioAssay Ontology to include pharmacokinetic/pharmacodynamic terminology for the enrichment of scientific workflows.

With the capacity to produce and record data electronically, Scientific research and the data associated with it have grown at an unprecedented rate. However, despite a decent amount of data now existing in an electronic form, it is still common for scientific research to be recorded in an unstructured text format with inconsistent context (vocabularies) which vastly reduces the potential for direct intelligent analysis. Research has demonstrated that the use of semantic technologies such as ontologies to structure and enrich scientific data can greatly improve this potential. However, whilst there are many ontologies that can be used for this purpose, there is still a vast quantity of scientific terminology that does not have adequate semantic representation. A key area for expansion identified by the authors was the pharmacokinetic/pharmacodynamic (PK/PD) domain due to its high usage across many areas of Pharma. As such we have produced a set of these terms and other bioassay related terms to be incorporated into the BioAssay Ontology (BAO), which was identified as the most relevant ontology for this work. A number of use cases developed by experts in the field were used to demonstrate how these new ontology terms can be used, and to set the scene for the continuation of this work with a look to expanding this work out into further relevant domains. The work done in this paper was part of Phase 1 of the SEED project (Semantically Enriching electronic laboratory notebook (eLN) Data).

NCTC3000: a century of bacterial strain collecting leads to a rich genomic data resource.

The National Collection of Type Cultures (NCTC) was founded on 1 January 1920 in order to fulfil a recognized need for a centralized repository for bacterial and fungal strains within the UK. It is among the longest-established collections of its kind anywhere in the world and today holds approximately 6000 type and reference bacterial strains - many of medical, scientific and veterinary importance - available to academic, health, food and veterinary institutions worldwide. Recently, a collaboration between NCTC, Pacific Biosciences and the Wellcome Sanger Institute established the NCTC3000 project to long-read sequence and assemble the genomes of up to 3000 NCTC strains. Here, at the beginning of the collection's second century, we introduce the resulting NCTC3000 sequence read datasets, genome assemblies and annotations as a unique, historically and scientifically relevant resource for the benefit of the international bacterial research community.

Systematic Review: Effectiveness of psychosocial interventions on wellbeing outcomes for adolescent or adult victim/survivors of recent rape or sexual assault.

Sexual assault and rape are common forms of sexual violence/abuse. The psychological/health consequences represent significant and ongoing harm. It seems imperative that victim/survivors receive evidence-based support within first response settings. To assess what psychosocial interventions work for victim/survivors of a recent sexual assault. Twenty-seven electronic databases were systematically searched. Narrative data synthesis was used to read across studies. Reporting format follows PRISMA checklist. Ten studies were identifed including range of interventions. The evidence is sparse and scientifically weak, common flaws are reviewed. There is some weak evidence for the impact of video and cognitive behavioural therapy (CBT) based interventions, especially trauma processing. There is a gap in the evidence base on psychosocial interventions for victim/survivors of sexual assault and higher quality research is required.

How the gene ontology evolves.

BACKGROUND: Maintaining a bio-ontology in the long term requires improving and updating its contents so that it adequately captures what is known about biological phenomena. This paper illustrates how these processes are carried out, by studying the ways in which curators at the Gene Ontology have hitherto incorporated new knowledge into their resource. RESULTS: Five types of circumstances are singled out as warranting changes in the ontology: (1) the emergence of anomalies within GO; (2) the extension of the scope of GO; (3) divergence in how terminology is used across user communities; (4) new discoveries that change the meaning of the terms used and their relations to each other; and (5) the extension of the range of relations used to link entities or processes described by GO terms. CONCLUSION: This study illustrates the difficulties involved in applying general standards to the development of a specific ontology. Ontology curation aims to produce a faithful representation of knowledge domains as they keep developing, which requires the translation of general guidelines into specific representations of reality and an understanding of how scientific knowledge is produced and constantly updated. In this context, it is important that trained curators with technical expertise in the scientific field(s) in question are involved in supervising ontology shifts and identifying inaccuracies.

Cross-product extensions of the Gene Ontology.

The Gene Ontology (GO) consists of nearly 30,000 classes for describing the activities and locations of gene products. Manual maintenance of ontology of this size is a considerable effort, and errors and inconsistencies inevitably arise. Reasoners can be used to assist with ontology development, automatically placing classes in a subsumption hierarchy based on their properties. However, the historic lack of computable definitions within the GO has prevented the user of these tools. In this paper, we present preliminary results of an ongoing effort to normalize the GO by explicitly stating the definitions of compositional classes in a form that can be used by reasoners. These definitions are partitioned into mutually exclusive cross-product sets, many of which reference other OBO Foundry candidate ontologies for chemical entities, proteins, biological qualities and anatomical entities. Using these logical definitions we are gradually beginning to automate many aspects of ontology development, detecting errors and filling in missing relationships. These definitions also enhance the GO by weaving it into the fabric of a wider collection of interoperating ontologies, increasing opportunities for data integration and enhancing genomic analyses.

Survey-based naming conventions for use in OBO Foundry ontology development.

BACKGROUND: A wide variety of ontologies relevant to the biological and medical domains are available through the OBO Foundry portal, and their number is growing rapidly. Integration of these ontologies, while requiring considerable effort, is extremely desirable. However, heterogeneities in format and style pose serious obstacles to such integration. In particular, inconsistencies in naming conventions can impair the readability and navigability of ontology class hierarchies, and hinder their alignment and integration. While other sources of diversity are tremendously complex and challenging, agreeing a set of common naming conventions is an achievable goal, particularly if those conventions are based on lessons drawn from pooled practical experience and surveys of community opinion. RESULTS: We summarize a review of existing naming conventions and highlight certain disadvantages with respect to general applicability in the biological domain. We also present the results of a survey carried out to establish which naming conventions are currently employed by OBO Foundry ontologies and to determine what their special requirements regarding the naming of entities might be. Lastly, we propose an initial set of typographic, syntactic and semantic conventions for labelling classes in OBO Foundry ontologies. CONCLUSION: Adherence to common naming conventions is more than just a matter of aesthetics. Such conventions provide guidance to ontology creators, help developers avoid flaws and inaccuracies when editing, and especially when interlinking, ontologies. Common naming conventions will also assist consumers of ontologies to more readily understand what meanings were intended by the authors of ontologies used in annotating bodies of data.

Ontology mapping for semantically enabled applications.

In this review, we provide a summary of recent progress in ontology mapping (OM) at a crucial time when biomedical research is under a deluge of an increasing amount and variety of data. This is particularly important for realising the full potential of semantically enabled or enriched applications and for meaningful insights, such as drug discovery, using machine-learning technologies. We discuss challenges and solutions for better ontology mappings, as well as how to select ontologies before their application. In addition, we describe tools and algorithms for ontology mapping, including evaluation of tool capability and quality of mappings. Finally, we outline the requirements for an ontology mapping service (OMS) and the progress being made towards implementation of such sustainable services.

The ins and outs of eukaryotic viruses: Knowledge base and ontology of a viral infection.

Viruses are genetically diverse, infect a wide range of tissues and host cells and follow unique processes for replicating themselves. All these processes were investigated and indexed in ViralZone knowledge base. To facilitate standardizing data, a simple ontology of viral life-cycle terms was developed to provide a common vocabulary for annotating data sets. New terminology was developed to address unique viral replication cycle processes, and existing terminology was modified and adapted. The virus life-cycle is classically described by schematic pictures. Using this ontology, it can be represented by a combination of successive terms: "entry", "latency", "transcription", "replication" and "exit". Each of these parts is broken down into discrete steps. For example Zika virus "entry" is broken down in successive steps: "Attachment", "Apoptotic mimicry", "Viral endocytosis/ macropinocytosis", "Fusion with host endosomal membrane", "Viral factory". To demonstrate the utility of a standard ontology for virus biology, this work was completed by annotating virus data in the ViralZone, UniProtKB and Gene Ontology databases.

The Gene Ontology of eukaryotic cilia and flagella.

BACKGROUND: Recent research into ciliary structure and function provides important insights into inherited diseases termed ciliopathies and other cilia-related disorders. This wealth of knowledge needs to be translated into a computational representation to be fully exploitable by the research community. To this end, members of the Gene Ontology (GO) and SYSCILIA Consortia have worked together to improve representation of ciliary substructures and processes in GO. METHODS: Members of the SYSCILIA and Gene Ontology Consortia suggested additions and changes to GO, to reflect new knowledge in the field. The project initially aimed to improve coverage of ciliary parts, and was then broadened to cilia-related biological processes. Discussions were documented in a public tracker. We engaged the broader cilia community via direct consultation and by referring to the literature. Ontology updates were implemented via ontology editing tools. RESULTS: So far, we have created or modified 127 GO terms representing parts and processes related to eukaryotic cilia/flagella or prokaryotic flagella. A growing number of biological pathways are known to involve cilia, and we continue to incorporate this knowledge in GO. The resulting expansion in GO allows more precise representation of experimentally derived knowledge, and SYSCILIA and GO biocurators have created 199 annotations to 50 human ciliary proteins. The revised ontology was also used to curate mouse proteins in a collaborative project. The revised GO and annotations, used in comparative 'before and after' analyses of representative ciliary datasets, improve enrichment results significantly. CONCLUSIONS: Our work has resulted in a broader and deeper coverage of ciliary composition and function. These improvements in ontology and protein annotation will benefit all users of GO enrichment analysis tools, as well as the ciliary research community, in areas ranging from microscopy image annotation to interpretation of high-throughput studies. We welcome feedback to further enhance the representation of cilia biology in GO.

Quality assurance of the gene ontology using abstraction networks.

The gene ontology (GO) is used extensively in the field of genomics. Like other large and complex ontologies, quality assurance (QA) efforts for GO's content can be laborious and time consuming. Abstraction networks (AbNs) are summarization networks that reveal and highlight high-level structural and hierarchical aggregation patterns in an ontology. They have been shown to successfully support QA work in the context of various ontologies. Two kinds of AbNs, called the area taxonomy and the partial-area taxonomy, are developed for GO hierarchies and derived specifically for the biological process (BP) hierarchy. Within this framework, several QA heuristics, based on the identification of groups of anomalous terms which exhibit certain taxonomy-defined characteristics, are introduced. Such groups are expected to have higher error rates when compared to other terms. Thus, by focusing QA efforts on anomalous terms one would expect to find relatively more erroneous content. By automatically identifying these potential problem areas within an ontology, time and effort will be saved during manual reviews of GO's content. BP is used as a testbed, with samples of three kinds of anomalous BP terms chosen for a taxonomy-based QA review. Additional heuristics for QA are demonstrated. From the results of this QA effort, it is observed that different kinds of inconsistencies in the modeling of GO can be exposed with the use of the proposed heuristics. For comparison, the results of QA work on a sample of terms chosen from GO's general population are presented.

A drug target slim: using gene ontology and gene ontology annotations to navigate protein-ligand target space in ChEMBL.

BACKGROUND: The process of discovering new drugs is a lengthy, time-consuming and expensive process. Modern day drug discovery relies heavily on the rapid identification of novel 'targets', usually proteins that can be modulated by small molecule drugs to cure or minimise the effects of a disease. Of the 20,000 proteins currently reported as comprising the human proteome, just under a quarter of these can potentially be modulated by known small molecules Storing information in curated, actively maintained drug discovery databases can help researchers access current drug discovery information quickly. However with the increase in the amount of data generated from both experimental and in silico efforts, databases can become very large very quickly and information retrieval from them can become a challenge. The development of database tools that facilitate rapid information retrieval is important to keep up with the growth of databases. DESCRIPTION: We have developed a Gene Ontology-based navigation tool (Gene Ontology Tree) to help users retrieve biological information to single protein targets in the ChEMBL drug discovery database. 99 % of single protein targets in ChEMBL have at least one GO annotation associated with them. There are 12,500 GO terms associated to 6200 protein targets in the ChEMBL database resulting in a total of 140,000 annotations. The slim we have created, the 'ChEMBL protein target slim' allows broad categorisation of the biology of 90 % of the protein targets using just 300 high level, informative GO terms. We used the GO slim method of assigning fewer higher level GO groupings to numerous very specific lower level terms derived from the GOA to describe a set of GO terms relevant to proteins in ChEMBL. We then used the slim created to provide a web based tool that allows a quick and easy navigation of protein target space. Terms from the GO are used to capture information on protein molecular function, biological process and subcellular localisations. The ChEMBL database also provides compound information for small molecules that have been tested for their effects on these protein targets. The 'ChEMBL protein target slim' provides a means of firstly describing the biology of protein drug targets and secondly allows users to easily establish a connection between biological and chemical information regarding drugs and drug targets in ChEMBL. The 'ChEMBL protein target slim' is available as a browsable 'Gene Ontology Tree' on the ChEMBL site under the browse targets tab ( https://www.ebi.ac.uk/chembl/target/browser ). A ChEMBL protein target slim OBO file containing the GO slim terms pertinent to ChEMBL is available from the GOC website ( http://geneontology.org/page/go-slim-and-subset-guide ). CONCLUSIONS: We have created a protein target navigation tool based on the 'ChEMBL protein target slim'. The 'ChEMBL protein target slim' provides a way of browsing protein targets in ChEMBL using high level GO terms that describe the molecular functions, processes and subcellular localisations of protein drug targets in drug discovery. The tool also allows user to establish a link between ontological groupings representing protein target biology to relevant compound information in ChEMBL. We have demonstrated by the use of a simple example how the 'ChEMBL protein target slim' can be used to link biological processes with drug information based on the information in the ChEMBL database. The tool has potential to aid in areas of drug discovery such as drug repurposing studies or drug-disease-protein pathways.

Genetic resources for methane production from biomass described with the Gene Ontology.

Methane (CH4) is a valuable fuel, constituting 70-95% of natural gas, and a potent greenhouse gas. Release of CH4 into the atmosphere contributes to climate change. Biological CH4 production or methanogenesis is mostly performed by methanogens, a group of strictly anaerobic archaea. The direct substrates for methanogenesis are H2 plus CO2, acetate, formate, methylamines, methanol, methyl sulfides, and ethanol or a secondary alcohol plus CO2. In numerous anaerobic niches in nature, methanogenesis facilitates mineralization of complex biopolymers such as carbohydrates, lipids and proteins generated by primary producers. Thus, methanogens are critical players in the global carbon cycle. The same process is used in anaerobic treatment of municipal, industrial and agricultural wastes, reducing the biological pollutants in the wastes and generating methane. It also holds potential for commercial production of natural gas from renewable resources. This process operates in digestive systems of many animals, including cattle, and humans. In contrast, in deep-sea hydrothermal vents methanogenesis is a primary production process, allowing chemosynthesis of biomaterials from H2 plus CO2. In this report we present Gene Ontology (GO) terms that can be used to describe processes, functions and cellular components involved in methanogenic biodegradation and biosynthesis of specialized coenzymes that methanogens use. Some of these GO terms were previously available and the rest were generated in our Microbial Energy Gene Ontology (MENGO) project. A recently discovered non-canonical CH4 production process is also described. We have performed manual GO annotation of selected methanogenesis genes, based on experimental evidence, providing "gold standards" for machine annotation and automated discovery of methanogenesis genes or systems in diverse genomes. Most of the GO-related information presented in this report is available at the MENGO website (http://www.mengo.biochem.vt.edu/).

Genetic resources for advanced biofuel production described with the Gene Ontology.

Dramatic increases in research in the area of microbial biofuel production coupled with high-throughput data generation on bioenergy-related microbes has led to a deluge of information in the scientific literature and in databases. Consolidating this information and making it easily accessible requires a unified vocabulary. The Gene Ontology (GO) fulfills that requirement, as it is a well-developed structured vocabulary that describes the activities and locations of gene products in a consistent manner across all kingdoms of life. The Microbial ENergy processes Gene Ontology () project is extending the GO to include new terms to describe microbial processes of interest to bioenergy production. Our effort has added over 600 bioenergy related terms to the Gene Ontology. These terms will aid in the comprehensive annotation of gene products from diverse energy-related microbial genomes. An area of microbial energy research that has received a lot of attention is microbial production of advanced biofuels. These include alcohols such as butanol, isopropanol, isobutanol, and fuels derived from fatty acids, isoprenoids, and polyhydroxyalkanoates. These fuels are superior to first generation biofuels (ethanol and biodiesel esterified from vegetable oil or animal fat), can be generated from non-food feedstock sources, can be used as supplements or substitutes for gasoline, diesel and jet fuels, and can be stored and distributed using existing infrastructure. Here we review the roles of genes associated with synthesis of advanced biofuels, and at the same time introduce the use of the GO to describe the functions of these genes in a standardized way.

An integrated ontology resource to explore and study host-virus relationships.

Our growing knowledge of viruses reveals how these pathogens manage to evade innate host defenses. A global scheme emerges in which many viruses usurp key cellular defense mechanisms and often inhibit the same components of antiviral signaling. To accurately describe these processes, we have generated a comprehensive dictionary for eukaryotic host-virus interactions. This controlled vocabulary has been detailed in 57 ViralZone resource web pages which contain a global description of all molecular processes. In order to annotate viral gene products with this vocabulary, an ontology has been built in a hierarchy of UniProt Knowledgebase (UniProtKB) keyword terms and corresponding Gene Ontology (GO) terms have been developed in parallel. The results are 65 UniProtKB keywords related to 57 GO terms, which have been used in 14,390 manual annotations; 908,723 automatic annotations and propagated to an estimation of 922,941 GO annotations. ViralZone pages, UniProtKB keywords and GO terms provide complementary tools to users, and the three resources have been linked to each other through host-virus vocabulary.

TermGenie - a web-application for pattern-based ontology class generation.

BACKGROUND: Biological ontologies are continually growing and improving from requests for new classes (terms) by biocurators. These ontology requests can frequently create bottlenecks in the biocuration process, as ontology developers struggle to keep up, while manually processing these requests and create classes. RESULTS: TermGenie allows biocurators to generate new classes based on formally specified design patterns or templates. The system is web-based and can be accessed by any authorized curator through a web browser. Automated rules and reasoning engines are used to ensure validity, uniqueness and relationship to pre-existing classes. In the last 4 years the Gene Ontology TermGenie generated 4715 new classes, about 51.4% of all new classes created. The immediate generation of permanent identifiers proved not to be an issue with only 70 (1.4%) obsoleted classes. CONCLUSION: TermGenie is a web-based class-generation system that complements traditional ontology development tools. All classes added through pre-defined templates are guaranteed to have OWL equivalence axioms that are used for automatic classification and in some cases inter-ontology linkage. At the same time, the system is simple and intuitive and can be used by most biocurators without extensive training.

Interdisciplinary perspectives on the development, integration, and application of cognitive ontologies.

We discuss recent progress in the development of cognitive ontologies and summarize three challenges in the coordinated development and application of these resources. Challenge 1 is to adopt a standardized definition for cognitive processes. We describe three possibilities and recommend one that is consistent with the standard view in cognitive and biomedical sciences. Challenge 2 is harmonization. Gaps and conflicts in representation must be resolved so that these resources can be combined for mark-up and interpretation of multi-modal data. Finally, Challenge 3 is to test the utility of these resources for large-scale annotation of data, search and query, and knowledge discovery and integration. As term definitions are tested and revised, harmonization should enable coordinated updates across ontologies. However, the true test of these definitions will be in their community-wide adoption which will test whether they support valid inferences about psychological and neuroscientific data.