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Over the 14 years, the Bio-Ontologies SIG at ISMB has provided a forum for discussion of the latest and most innovative research in the bio-ontologies development, its applications to biomedicine and more generally the organisation, presentation and dissemination of knowledge in biomedicine and the life sciences. The seven papers selected for this supplement span a wide range of topics including: web-based querying over multiple ontologies, integration of data from wikis, innovative methods of annotating and mining electronic health records, advances in annotating web documents and biomedical literature, quality control of ontology alignments, and the ontology support for predictive models about toxicity and open access to the toxicity data.

© 2013 Soldatova et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Over the 15 years, the Bio-Ontologies SIG at ISMB has provided a forum for discussion of the latest and most innovative research in the bio-ontologies development, its applications to biomedicine and more generally the organisation, presentation and dissemination of knowledge in biomedicine and the life sciences. The seven papers and the commentary selected for this supplement span a wide range of topics including: web-based querying over multiple ontologies, integration of data, annotating patent records, NCBO Web services, ontology developments for probabilistic reasoning and for physiological processes, and analysis of the progress of annotation and structural GO changes.

The World Wide Web has become a dissemination platform for scientific and non-scientific publications. However, most of the information remains locked up in discrete documents that are not always interconnected or machine-readable. The connectivity tissue provided by RDF technology has not yet been widely used to support the generation of self-describing, machine-readable documents. In this paper, we present our approach to the generation of self-describing machine-readable scholarly documents. We understand the scientific document as an entry point and interface to the Web of Data. We have semantically processed the full-text, open-access subset of PubMed Central. Our RDF model and resulting dataset make extensive use of existing ontologies and semantic enrichment services. We expose our model, services, prototype, and datasets at http://biotea.idiginfo.org/ The semantic processing of biomedical literature presented in this paper embeds documents within the Web of Data and facilitates the execution of concept-based queries against the entire digital library. Our approach delivers a flexible and adaptable set of tools for metadata enrichment and semantic processing of biomedical documents. Our model delivers a semantically rich and highly interconnected dataset with self-describing content so that software can make effective use of it.

Background Scientific activity for 3D bioprinting has increased over the past years focusing mainly on fully functional biological constructs to overcome issues related to organ transplants. This research performs a scientometric analysis on bioprinting based on a competitive technology intelligence (CTI) cycle, which assesses scientific documents to establish the publication rate of science and technology in terms of institutions, patents or journals. Although analyses of publications can be observed in the literature, the identification of the most influential authors and affiliations has not been addressed. This study involves the analysis of authors and affiliations, and their interactions in a global framework. We use network collaboration maps and Betweenness Centrality (BC) to identify of the most prominent actors in bioprinting, enhancing the CTI analysis. Results 2088 documents were retrieved from Scopus database from 2007 to 2017, disclosing an exponential growth with an average publication increase of 17.5% per year. A threshold of five articles with ten or more cites was established for authors, while the same number of articles but cited five or more times was set for affiliations. The author with more publications was Atala A. (36 papers and a BC = 370.9), followed by Khademhosseini A. (30 documents and a BC = 2104.7), and Mironov (30 documents and BC = 2754.9). In addition, a small correlation was observed between the number of collaborations and the number of publications. Furthermore, 1760 institutions with a median of 10 publications were found, but only 20 within the established threshold. 30% of the 20 institutions had an external collaboration, and institutions located in and close to the life science cluster in Massachusetts showed a strong cooperation. The institution with more publications was the Harvard Medical School, 61 publications, followed by the Brigham and Women’s hospital, 46 papers, and the Massachusetts Institute of Technology with 37 documents. Conclusions Network map analysis and BC allowed the identification of the most influential authors working on bioprinting and the collaboration between institutions was found limited. This analysis of authors and affiliations and their collaborations offer valuable information for the identification of potential associations for bioprinting researches and stakeholders.

Background Most tutorial ontologies focus on illustrating one aspect of ontology development, notably language features and automated reasoners, but ignore ontology development factors, such as emergent modelling guidelines and ontological principles. Yet, novices replicate examples from the exercise they carry out. Not providing good examples holistically causes the propagation of sub-optimal ontology development, which may negatively affect the quality of a real domain ontology. Results We identified 22 requirements that a good tutorial ontology should satisfy regarding subject domain, logics and reasoning, and engineering aspects. We developed a set of ontologies about African Wildlife to serve as tutorial ontologies. A majority of the requirements have been met with the set of African Wildlife Ontology tutorial ontologies, which are introduced in this paper. The African Wildlife Ontology is mature and has been used yearly in an ontology engineering course or tutorial since 2010 and is included in a recent ontology engineering textbook with relevant examples and exercises. Conclusion The African Wildlife Ontology provides a wide range of options concerning examples and exercises for ontology engineering well beyond illustrating just language features and automated reasoning. It assists in demonstrating tasks concerning ontology quality, such as alignment to a foundational ontology and satisfying competency questions, versioning, and multilingual ontologies.

Background Biological databases vary enormously in size and data complexity, from small databases that contain a few million Resource Description Framework (RDF) triples to large databases that contain billions of triples. In this paper, we evaluate whether RDF native stores can be used to meet the needs of a biological database provider. Prior evaluations have used synthetic data with a limited database size. For example, the largest BSBM benchmark uses 1 billion synthetic e-commerce knowledge RDF triples on a single node. However, real world biological data differs from the simple synthetic data much. It is difficult to determine whether the synthetic e-commerce data is efficient enough to represent biological databases. Therefore, for this evaluation, we used five real data sets from biological databases. Results We evaluated five triple stores, 4store, Bigdata, Mulgara, Virtuoso, and OWLIM-SE, with five biological data sets, Cell Cycle Ontology, Allie, PDBj, UniProt, and DDBJ, ranging in size from approximately 10 million to 8 billion triples. For each database, we loaded all the data into our single node and prepared the database for use in a classical data warehouse scenario. Then, we ran a series of SPARQL queries against each endpoint and recorded the execution time and the accuracy of the query response. Conclusions Our paper shows that with appropriate configuration Virtuoso and OWLIM-SE can satisfy the basic requirements to load and query biological data less than 8 billion or so on a single node, for the simultaneous access of 64 clients. OWLIM-SE performs best for databases with approximately 11 million triples; For data sets that contain 94 million and 590 million triples, OWLIM-SE and Virtuoso perform best. They do not show overwhelming advantage over each other; For data over 4 billion Virtuoso works best. 4store performs well on small data sets with limited features when the number of triples is less than 100 million, and our test shows its scalability is poor; Bigdata demonstrates average performance and is a good open source triple store for middle-sized (500 million or so) data set; Mulgara shows a little of fragility.

Background Social risk factors are important dimensions of health and are linked to access to care, quality of life, health outcomes and life expectancy. However, in the Electronic Health Record, data related to many social risk factors are primarily recorded in free-text clinical notes, rather than as more readily computable structured data, and hence cannot currently be easily incorporated into automated assessments of health. In this paper, we present Moonstone, a new, highly configurable rule-based clinical natural language processing system designed to automatically extract information that requires inferencing from clinical notes. Our initial use case for the tool is focused on the automatic extraction of social risk factor information — in this case, housing situation, living alone, and social support — from clinical notes. Nursing notes, social work notes, emergency room physician notes, primary care notes, hospital admission notes, and discharge summaries, all derived from the Veterans Health Administration, were used for algorithm development and evaluation. Results An evaluation of Moonstone demonstrated that the system is highly accurate in extracting and classifying the three variables of interest (housing situation, living alone, and social support). The system achieved positive predictive value (i.e. precision) scores ranging from 0.66 (homeless/marginally housed) to 0.98 (lives at home/not homeless), accuracy scores ranging from 0.63 (lives in facility) to 0.95 (lives alone), and sensitivity (i.e. recall) scores ranging from 0.75 (lives in facility) to 0.97 (lives alone). Conclusions The Moonstone system is — to the best of our knowledge — the first freely available, open source natural language processing system designed to extract social risk factors from clinical text with good (lives in facility) to excellent (lives alone) performance. Although developed with the social risk factor identification task in mind, Moonstone provides a powerful tool to address a range of clinical natural language processing tasks, especially those tasks that require nuanced linguistic processing in conjunction with inference capabilities.

Background Information technology has the potential to increase the pace of scientific progress by helping researchers in formulating, publishing and finding information. There are numerous projects that employ ontologies and Semantic Web technologies towards this goal. However, the number of applications that have found widespread use among biomedical researchers is still surprisingly small. In this paper we present the aTag (‘associative tags’) convention, which aims to drastically lower the entry barriers to the biomedical Semantic Web. aTags are short snippets of HTML+RDFa with embedded RDF/OWL based on the Semantically Interlinked Online Communities (SIOC) vocabulary and domain ontologies and taxonomies, such as the Open Biomedical Ontologies and DBpedia. The structure of aTags is very simple: a short piece of human-readable text that is ‘tagged’ with relevant ontological entities. This paper describes our efforts for seeding the creation of a viable ecosystem of datasets, tools and services around aTags. Results Numerous biomedical datasets in aTag format and systems for the creation of aTags have been set-up and are described in this paper. Prototypes of some of these systems are accessible at http://hcls.deri.org/atag Conclusions The aTags convention enables the rapid development of diverse, integrated datasets and semantically interoperable applications. More work needs to be done to study the practicability of this approach in different use-case scenarios, and to encourage uptake of the convention by other groups.

Background Even though several high-quality clinical terminologies, such as SNOMED CT and LOINC, are readily available, uptake in clinical systems has been slow and many continue to capture information in plain text or using custom terminologies. This paper discusses some of the challenges behind this slow uptake and describes a clinical terminology server implementation that aims to overcome these obstacles and contribute to the widespread adoption of standardised clinical terminologies. Results Ontoserver is a clinical terminology server based on the Fast Health Interoperability Resources (FHIR) standard. Some of its key features include: out-of-the-box support for SNOMED CT, LOINC and OWL ontologies, such as the Human Phenotype Ontology (HPO); a fast, prefix-based search algorithm to ensure users can easily find content and are not discouraged from entering coded data; a syndication mechanism to facilitate keeping terminologies up to date; and a full implementation of SNOMED CT’s Expression Constraint Language (ECL), which enables sophisticated data analytics. Conclusions Ontoserver has been designed to overcome some of the challenges that have hindered adoption of standardised clinical terminologies and is used in several organisations throughout Australia. Increasing adoption is an important goal because it will help improve the quality of clinical data, which can lead to better clinical decision support and ultimately to better patient outcomes.

Background Treatment of type 2 diabetes mellitus (T2DM) is a complex problem. A clinical decision support system (CDSS) based on massive and distributed electronic health record data can facilitate the automation of this process and enhance its accuracy. The most important component of any CDSS is its knowledge base. This knowledge base can be formulated using ontologies. The formal description logic of ontology supports the inference of hidden knowledge. Building a complete, coherent, consistent, interoperable, and sharable ontology is a challenge. Results This paper introduces the first version of the newly constructed Diabetes Mellitus Treatment Ontology (DMTO) as a basis for shared-semantics, domain-specific, standard, machine-readable, and interoperable knowledge relevant to T2DM treatment. It is a comprehensive ontology and provides the highest coverage and the most complete picture of coded knowledge about T2DM patients’ current conditions, previous profiles, and T2DM-related aspects, including complications, symptoms, lab tests, interactions, treatment plan (TP) frameworks, and glucose-related diseases and medications. It adheres to the design principles recommended by the Open Biomedical Ontologies Foundry and is based on ontological realism that follows the principles of the Basic Formal Ontology and the Ontology for General Medical Science. DMTO is implemented under Protégé 5.0 in Web Ontology Language (OWL) 2 format and is publicly available through the National Center for Biomedical Ontology’s BioPortal at http://bioportal.bioontology.org/ontologies/DMTO. The current version of DMTO includes more than 10,700 classes, 277 relations, 39,425 annotations, 214 semantic rules, and 62,974 axioms. We provide proof of concept for this approach to modeling TPs. Conclusion The ontology is able to collect and analyze most features of T2DM as well as customize chronic TPs with the most appropriate drugs, foods, and physical exercises. DMTO is ready to be used as a knowledge base for semantically intelligent and distributed CDSS systems. Electronic supplementary material The online version of this article (10.1186/s13326-018-0176-y) contains supplementary material, which is available to authorized users.

Background: Semantic interoperability is essential when carrying out post-genomic clinical trials where several institutions collaborate, since researchers and developers need to have an integrated view and access to heterogeneous data sources. One possible approach to accommodate this need is to use RDB2RDF systems that provide RDF datasets as the unified view. These RDF datasets may be materialized and stored in a triple store, or transformed into RDF in real time, as virtual RDF data sources. Our previous efforts involved materialized RDF datasets, hence losing data freshness.Results: In this paper we present a solution that uses an ontology based on the HL7 v3 Reference Information Model and a set of R2RML mappings that relate this ontology to an underlying relational database implementation, and where morph-RDB is used to expose a virtual, non-materialized SPARQL endpoint over the data.Conclusions: By applying a set of optimization techniques on the SPARQL-to-SQL query translation algorithm, we can now issue SPARQL queries to the underlying relational data with generally acceptable performance.

In this paper, we describe a histological ontology of the human cardiovascular system developed in collaboration among histology experts and computer scientists. The histological ontology is developed following an existing methodology using Conceptual Models (CMs) and validated using OOPS!, expert evaluation with CMs, and how accurately the ontology can answer the Competency Questions (CQ). It is publicly available at http://bioportal.bioontology.org/ontologies/HO and https://w3id.org/def/System . The histological ontology is developed to support complex tasks, such as supporting teaching activities, medical practices, and bio-medical research or having natural language interactions.

Background In recent years, numerous computational methods predicted protein function based on the protein-protein interaction (PPI) network. These methods supposed that two proteins share the same function if they interact with each other. However, it is reported by recent studies that the functions of two interacting proteins may be just related. It will mislead the prediction of protein function. Therefore, there is a need for investigating the functional relationship between interacting proteins. Results In this paper, the functional relationship between interacting proteins is studied and a novel method, called as GoDIN, is advanced to annotate functions of interacting proteins in Gene Ontology (GO) context. It is assumed that the functional difference between interacting proteins can be expressed by semantic difference between GO term and its relatives. Thus, the method uses GO term and its relatives to annotate the interacting proteins separately according to their functional roles in the PPI network. The method is validated by a series of experiments and compared with the concerned method. The experimental results confirm the assumption and suggest that GoDIN is effective on predicting functions of protein. Conclusions This study demonstrates that: (1) interacting proteins are not equal in the PPI network, and their function may be same or similar, or just related; (2) functional difference between interacting proteins can be measured by their degrees in the PPI network; (3) functional relationship between interacting proteins can be expressed by relationship between GO term and its relatives.

Background Research for ontology evaluation is scarce. If biomedical ontological datasets and knowledgebases are to be widely used, there needs to be quality control and evaluation for the content and structure of the ontology. This paper introduces how to effectively utilize a semiotic-inspired approach to ontology evaluation, specifically towards drug-related ontologies hosted on the National Center for Biomedical Ontology BioPortal. Results Using the semiotic-based evaluation framework for drug-based ontologies, we adjusted the quality metrics based on the semiotic features of drug ontologies. Then, we compared the quality scores before and after tailoring. The scores revealed a more precise measurement and a closer distribution compared to the before-tailoring. Conclusion The results of this study reveal that a tailored semiotic evaluation produced a more meaningful and accurate assessment of drug-based ontologies, lending to the possible usefulness of semiotics in ontology evaluation.

The abundance and unstructured nature of biomedical texts, be it clinical or research content, impose significant challenges for the effective and efficient use of information and knowledge stored in such texts. Annotation of biomedical documents with machine intelligible semantics facilitates advanced, semantics-based text management, curation, indexing, and search. This paper focuses on annotation of biomedical entity mentions with concepts from relevant biomedical knowledge bases such as UMLS. As a result, the meaning of those mentions is unambiguously and explicitly defined, and thus made readily available for automated processing. This process is widely known as semantic annotation, and the tools that perform it are known as semantic annotators. Over the last dozen years, the biomedical research community has invested significant efforts in the development of biomedical semantic annotation technology. Aiming to establish grounds for further developments in this area, we review a selected set of state of the art biomedical semantic annotators, focusing particularly on general purpose annotators, that is, semantic annotation tools that can be customized to work with texts from any area of biomedicine. We also examine potential directions for further improvements of today’s annotators which could make them even more capable of meeting the needs of real-world applications. To motivate and encourage further developments in this area, along the suggested and/or related directions, we review existing and potential practical applications and benefits of semantic annotators.

Background Integrating multiple sources of pharmacovigilance evidence has the potential to advance the science of safety signal detection and evaluation. In this regard, there is a need for more research on how to integrate multiple disparate evidence sources while making the evidence computable from a knowledge representation perspective (i.e., semantic enrichment). Existing frameworks suggest well-promising outcomes for such integration but employ a rather limited number of sources. In particular, none have been specifically designed to support both regulatory and clinical use cases, nor have any been designed to add new resources and use cases through an open architecture. This paper discusses the architecture and functionality of a system called Large-scale Adverse Effects Related to Treatment Evidence Standardization (LAERTES) that aims to address these shortcomings. Results LAERTES provides a standardized, open, and scalable architecture for linking evidence sources relevant to the association of drugs with health outcomes of interest (HOIs). Standard terminologies are used to represent different entities. For example, drugs and HOIs are represented in RxNorm and Systematized Nomenclature of Medicine -- Clinical Terms respectively. At the time of this writing, six evidence sources have been loaded into the LAERTES evidence base and are accessible through prototype evidence exploration user interface and a set of Web application programming interface services. This system operates within a larger software stack provided by the Observational Health Data Sciences and Informatics clinical research framework, including the relational Common Data Model for observational patient data created by the Observational Medical Outcomes Partnership. Elements of the Linked Data paradigm facilitate the systematic and scalable integration of relevant evidence sources. Conclusions The prototype LAERTES system provides useful functionality while creating opportunities for further research. Future work will involve improving the method for normalizing drug and HOI concepts across the integrated sources, aggregated evidence at different levels of a hierarchy of HOI concepts, and developing more advanced user interface for drug-HOI investigations.

Background:The biomedical community has now developed a significant number of ontologies. The curation ofbiomedical ontologies is a complex task and biomedical ontologies evolve rapidly, so new versions are regularlyand frequently published in ontology repositories. This has the implication of there being a high number ofontology versions over a short time span. Given this level of activity, ontology designers need to be supportedin the effective management of the evolution of biomedical ontologies as the different changes may affect the engineering and quality of the ontology. This is why there is a need for methods that contribute to the analysisof the effects of changes and evolution of ontologies.Results:In this paper we approach this issue from the ontology quality perspective. In previous work we have developed an ontology evaluation framework based on quantitative metrics, called OQuaRE. Here, OQuaRE is used as a core component in a method that enables the analysis of the different versions of biomedicalontologies using the quality dimensions included in OQuaRE. Moreover, we describe and use two scales for evaluating the changes between the versions of a given ontology. The first one is the static scale used inOQuaRE and the second one is a new, dynamic scale, based on the observed values of the quality metrics of a corpus declined by all the versions of a given ontology (life-cycle). In this work we explain how OQuaRE can be adapted for understanding the evolution of ontologies. Its use has been illustrated with the ontology of bioinformatics operations, types of data, formats, and topics (EDAM).Conclusions:The two scales included in OQuaRE provide complementary information about the evolution of the ontologies. The application of the static scale, which is the original OQuaRE scale, to the versions of the EDAM ontology reveals a design based on good ontological engineering principles. The application of thedynamic scale has enabled a more detailed analysis of the evolution of the ontology, measured through differences between versions. The statistics of change based on the OQuaRE quality scores make possible to identify key versions where some changes in the engineering of the ontology triggered a change from the OQuaRE quality perspective. In the case of the EDAM, this study let us to identify that the fifth version of the ontology has the largest impact in the quality metrics of the ontology, when comparative analyses between the pairs of consecutive versions are performed.

Background: Twitter updates now represent an enormous stream of information originating from a wide variety of formal and informal sources, much of which is relevant to real-world events. They can therefore be highly useful for event detection and situational awareness applications. Results: In this paper we apply customised filtering techniques to existing bio-surveillance algorithms to detect localised spikes in Twitter activity, showing that these correspond to real events with a high level of confidence. We then develop a methodology to automatically summarise these events, both by providing the tweets which best describe the event and by linking to highly relevant news articles. This news linkage is accomplished by identifying terms occurring more frequently in the event tweets than in a baseline of activity for the area concerned, and using these to search for news. We apply our methods to outbreaks of illness and events strongly affecting sentiment and are able to detect events verifiable by third party sources and produce high quality summaries. Conclusions: This study demonstrates linking event detection from Twitter with relevant online news to provide situational awareness. This builds on the existing studies that focus on Twitter alone, showing that integrating information from multiple online sources can produce useful analysis.

As a special class of non-coding RNAs (ncRNAs), microRNAs (miRNAs) perform important roles in numerous biological and pathological processes. The realization of miRNA functions depends largely on how miRNAs regulate specific target genes. It is therefore critical to identify, analyze, and cross-reference miRNA-target interactions to better explore and delineate miRNA functions. Semantic technologies can help in this regard. We previously developed a miRNA domain-specific application ontology, Ontology for MIcroRNA Target (OMIT), whose goal was to serve as a foundation for semantic annotation, data integration, and semantic search in the miRNA field. In this paper we describe our continuing effort to develop the OMIT, and demonstrate its use within a semantic search system, OmniSearch, designed to facilitate knowledge capture of miRNA-target interaction data. Important changes in the current version OMIT are summarized as: (1) following a modularized ontology design (with 2559 terms imported from the NCRO ontology); (2) encoding all 1884 human miRNAs (vs. 300 in previous versions); and (3) setting up a GitHub project site along with an issue tracker for more effective community collaboration on the ontology development. The OMIT ontology is free and open to all users, accessible at: http://purl.obolibrary.org/obo/omit.owl. The OmniSearch system is also free and open to all users, accessible at: http://omnisearch.soc.southalabama.edu/index.php/Software.

Information about drug-drug interactions (DDIs) is crucial for computational applications such as pharmacovigilance and drug repurposing. However, existing sources of DDIs have the problems of low coverage, low accuracy and low agreement. One common type of DDIs is related to the mechanism of drug metabolism: a DDI relation may be caused by different interactions (e.g., substrate, inhibit) between drugs and enzymes in the drug metabolism process. Thus, information from drug enzyme interactions (DEIs) serves as important supportive evidence for DDIs. Further, potential DDIs present implicitly could be detected by inference and reasoning based on DEIs.In this article, we propose a hybrid approach to combining machine learning algorithm with trigger words and syntactic patterns, for DEI relation extraction from biomedical literature. The extracted DEI relations are used for reasoning to infer potential DDI relations, based on a defined drug-enzyme ontology incorporating biological knowledge.Evaluation results demonstrate that the performance of DEI relation extraction is promising, with an F-measure of 84.97% on the in vivo dataset and 65.58% on the in vitro dataset. Further, the inferred DDIs achieved a precision of 83.19% on the in vivo dataset and 70.94% on the in vitro dataset, respectively. A further examination showed that the overlaps between our inferred DDIs and those present in DrugBank were 42.02% on the in vivo dataset and 19.23 % on the in vitro dataset, respectively.This paper proposed an effective approach to extract DEI relations from biomedical literature. Potential DDIs not present in existing knowledge bases were then inferred based on the extracted DEIs, demonstrating the capability of the proposed approach to detect DDIs with scientific evidence for pharmacovigilance and drug repurposing applications.

Background: Ontologies are widely used both in the life sciences and in the management of public and private companies. Typically, the different offices in an organization develop their own models and related ontologies to capture specific tasks and goals. Although there might be an overall coordination, the use of distinct ontologies can jeopardize the integration of data across the organization since data sharing and reusability are sensitive to modeling choices. Results: The paper provides a study of the entities that are typically found at the reception, analysis and report phases in public institutes in the life science domain. Ontological considerations and techniques are introduced and their implementation exemplified by studying the Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), a public veterinarian institute with different geographical locations and several laboratories. Different modeling issues are discussed like the identification and characterization of the main entities in these phases; the classification of the (types of) data; the clarification of the contexts and the roles of the involved entities. The study is based on a foundational ontology and shows how it can be extended to a comprehensive and coherent framework comprising the different institute's roles, processes and data. In particular, it shows how to use notions lying at the borderline between ontology and applications, like that of knowledge object. The paper aims to help the modeler to understand the core viewpoint of the organization and to improve data transparency. Conclusions: The study shows that the entities at play can be analyzed within a single ontological perspective allowing us to isolate a single ontological framework for the whole organization. This facilitates the development of coherent representations of the entities and related data, and fosters the use of integrated software for data management and reasoning across the company.

Background There are several humanly defined ontologies relevant to Medline. However, Medline is a fast growing collection of biomedical documents which creates difficulties in updating and expanding these humanly defined ontologies. Automatically identifying meaningful categories of entities in a large text corpus is useful for information extraction, construction of machine learning features, and development of semantic representations. In this paper we describe and compare two methods for automatically learning meaningful biomedical categories in Medline. The first approach is a simple statistical method that uses part-of-speech and frequency information to extract a list of frequent nouns from Medline. The second method implements an alignment-based technique to learn frequent generic patterns that indicate a hyponymy/hypernymy relationship between a pair of noun phrases. We then apply these patterns to Medline to collect frequent hypernyms as potential biomedical categories. Results We study and compare these two alternative sets of terms to identify semantic categories in Medline. We find that both approaches produce reasonable terms as potential categories. We also find that there is a significant agreement between the two sets of terms. The overlap between the two methods improves our confidence regarding categories predicted by these independent methods. Conclusions This study is an initial attempt to extract categories that are discussed in Medline. Rather than imposing external ontologies on Medline, our methods allow categories to emerge from the text.

Background Biomedical ontologies usually encode knowledge that applies always or at least most of the time, that is in normal circumstances. But for some applications like phenotype ontologies it is becoming increasingly important to represent information about aberrations from a norm. These aberrations may be modifications of physiological structures, but also modifications of biological processes. Methods To facilitate precise definitions of process-related phenotypes, such as delayed eruption of the primary teeth or disrupted ocular pursuit movements, I introduce a modeling approach that draws inspiration from the use of continuations in the analysis of programming languages and apply a similar idea to ontological modeling. This approach characterises processes by describing their outcome up to a certain point and the way they will continue in the canonical case. Definitions of process types are then given in terms of their continuations and anomalous phenotypes are defined by their differences to the canonical definitions. Results The resulting model is capable of accurately representing structural process anomalies. It allows distinguishing between different anomaly kinds (delays, interruptions), gives identity criteria for interrupted processes, and explains why normal and anomalous process instances can be subsumed under a common type, thus establishing the connection between canonical and anomalous process-related phenotypes. Conclusion This paper shows how to to give semantically rich definitions of process-related phenotypes. These allow to expand the application areas of phenotype ontologies beyond literature annotation and establishment of genotype-phenotype associations to the detection of anomalies in suitably encoded datasets.

Background The large-scale effort in developing, maintaining and making biomedical ontologies available motivates the application of similarity measures to compare ontology concepts or, by extension, the entities described therein. A common approach, known as semantic similarity, compares ontology concepts through the information content they share in the ontology. However, different disjunctive ancestors in the ontology are frequently neglected, or not properly explored, by semantic similarity measures. Results This paper proposes a novel method, dubbed DiShIn, that effectively exploits the multiple inheritance relationships present in many biomedical ontologies. DiShIn calculates the shared information content of two ontology concepts, based on the information content of the disjunctive common ancestors of the concepts being compared. DiShIn identifies these disjunctive ancestors through the number of distinct paths from the concepts to their common ancestors. Conclusions DiShIn was applied to Gene Ontology and its performance was evaluated against state-of-the-art measures using CESSM, a publicly available evaluation platform of protein similarity measures. By modifying the way traditional semantic similarity measures calculate the shared information content, DiShIn was able to obtain a statistically significant higher correlation between semantic and sequence similarity. Moreover, the incorporation of DiShIn in existing applications that exploit multiple inheritance would reduce their execution time.

The papers presented in this supplement focus and reflect on computer use in every-day clinical work in hospitals and clinics such as electronic health record systems, pre-processing for computer aided summaries, clinical coding, computer decision systems, as well as related ethical concerns and security. Much of this work concerns itself by necessity with incorporation and development of language processing tools and methods, and as such this supplement aims at providing an arena for reporting on development in a diversity of languages. In the supplement we can read about some of the challenges identified above.

Background In this paper we present a detailed scheme for annotating medical web pages designed for health care consumers. The annotation is along two axes: first, by reliability (the extent to which the medical information on the page can be trusted), second, by the type of page (patient leaflet, commercial, link, medical article, testimonial, or support). Results We analyze inter-rater agreement among three judges for each axis. Inter-rater agreement was moderate (0.77 accuracy, 0.62 F-measure, 0.49 Kappa) on the page reliability axis and good (0.81 accuracy, 0.72 F-measure, 0.73 Kappa) along the page type axis. Conclusions We have shown promising results in this study that appropriate classes of pages can be developed and used by human annotators to annotate web pages with reasonable to good agreement. Availability No.

In this paper, we show how we have applied the Clinical Narrative Temporal Relation Ontology (CNTRO) and its associated temporal reasoning system (the CNTRO Timeline Library) to trend temporal information within medical device adverse event report narratives. 238 narratives documenting occurrences of late stent thrombosis adverse events from the Food and Drug Administration’s (FDA) Manufacturing and User Facility Device Experience (MAUDE) database were annotated and evaluated using the CNTRO Timeline Library to identify, order, and calculate the duration of temporal events. The CNTRO Timeline Library had a 95% accuracy in correctly ordering events within the 238 narratives. 41 narratives included an event in which the duration was documented, and the CNTRO Timeline Library had an 80% accuracy in correctly determining these durations. 77 narratives included documentation of a duration between events, and the CNTRO Timeline Library had a 76% accuracy in determining these durations. This paper also includes an example of how this temporal output from the CNTRO ontology can be used to verify recommendations for length of drug administration, and proposes that these same tools could be applied to other medical device adverse event narratives in order to identify currently unknown temporal trends.

This paper presents an ontologically founded basic architecture for information systems, which are intended to capture, represent, and maintain metadata for various domains of clinical and epidemiological research. Clinical trials exhibit an important basis for clinical research, and the accurate specification of metadata and their documentation and application in clinical and epidemiological study projects represents a significant expense in the project preparation and has a relevant impact on the value and quality of these studies. An ontological foundation of an information system provides a semantic framework for the precise specification of those entities which are presented in this system. This semantic framework should be grounded, according to our approach, on a suitable top-level ontology. Such an ontological foundation leads to a deeper understanding of the entities of the domain under consideration, and provides a common unifying semantic basis, which supports the integration of data and the interoperability between different information systems. The intended information systems will be applied to the field of clinical and epidemiological research and will provide, depending on the application context, a variety of functionalities. In the present paper, we focus on a basic architecture which might be common to all such information systems. The research, set forth in this paper, is included in a broader framework of clinical research and continues the work of the IMISE on these topics.

Background This paper presents a novel approach to the problem of hedge detection, which involves identifying so-called hedge cues for labeling sentences as certain or uncertain. This is the classification problem for Task 1 of the CoNLL-2010 Shared Task, which focuses on hedging in the biomedical domain. We here propose to view hedge detection as a simple disambiguation problem, restricted to words that have previously been observed as hedge cues. As the feature space for the classifier is still very large, we also perform experiments with dimensionality reduction using the method of random indexing. Results The SVM-based classifiers developed in this paper achieves the best published results so far for sentence-level uncertainty prediction on the CoNLL-2010 Shared Task test data. We also show that the technique of random indexing can be successfully applied for reducing the dimensionality of the original feature space by several orders of magnitude, without sacrificing classifier performance. Conclusions This paper introduces a simplified approach to detecting speculation or uncertainty in text, focusing on the biomedical domain. Evaluated at the sentence-level, our SVM-based classifiers achieve the best published results so far. We also show that the feature space can be aggressively compressed using random indexing while still maintaining comparable classifier performance.

Background There is currently a gap between the rich and expressive collection of published biomedical ontologies, and the natural language expression of biomedical papers consumed on a daily basis by scientific researchers. The purpose of this paper is to provide an open, shareable structure for dynamic integration of biomedical domain ontologies with the scientific document, in the form of an Annotation Ontology (AO), thus closing this gap and enabling application of formal biomedical ontologies directly to the literature as it emerges. Methods Initial requirements for AO were elicited by analysis of integration needs between biomedical web communities, and of needs for representing and integrating results of biomedical text mining. Analysis of strengths and weaknesses of previous efforts in this area was also performed. A series of increasingly refined annotation tools were then developed along with a metadata model in OWL, and deployed for feedback and additional requirements the ontology to users at a major pharmaceutical company and a major academic center. Further requirements and critiques of the model were also elicited through discussions with many colleagues and incorporated into the work. Results This paper presents Annotation Ontology (AO), an open ontology in OWL-DL for annotating scientific documents on the web. AO supports both human and algorithmic content annotation. It enables “stand-off” or independent metadata anchored to specific positions in a web document by any one of several methods. In AO, the document may be annotated but is not required to be under update control of the annotator. AO contains a provenance model to support versioning, and a set model for specifying groups and containers of annotation. AO is freely available under open source license at http://purl.org/ao/, and extensive documentation including screencasts is available on AO’s Google Code page: http://code.google.com/p/annotation-ontology/ . Conclusions The Annotation Ontology meets critical requirements for an open, freely shareable model in OWL, of annotation metadata created against scientific documents on the Web. We believe AO can become a very useful common model for annotation metadata on Web documents, and will enable biomedical domain ontologies to be used quite widely to annotate the scientific literature. Potential collaborators and those with new relevant use cases are invited to contact the authors.

The lack of established standards to describe and annotate biological assays and screening outcomes in the domain of drug and chemical probe discovery is a severe limitation to utilize public and proprietary drug screening data to their maximum potential. We have created the BioAssay Ontology (BAO) project (http://bioassayontology.org) to develop common reference metadata terms and definitions required for describing relevant information of low-and high-throughput drug and probe screening assays and results. The main objectives of BAO are to enable effective integration, aggregation, retrieval, and analyses of drug screening data. Since we first released BAO on the BioPortal in 2010 we have considerably expanded and enhanced BAO and we have applied the ontology in several internal and external collaborative projects, for example the BioAssay Research Database (BARD). We describe the evolution of BAO with a design that enables modeling complex assays including profile and panel assays such as those in the Library of Integrated Network-based Cellular Signatures (LINCS). One of the critical questions in evolving BAO is the following: how can we provide a way to efficiently reuse and share among various research projects specific parts of our ontologies without violating the integrity of the ontology and without creating redundancies. This paper provides a comprehensive answer to this question with a description of a methodology for ontology modularization using a layered architecture. Our modularization approach defines several distinct BAO components and separates internal from external modules and domain-level from structural components. This approach facilitates the generation/extraction of derived ontologies (or perspectives) that can suit particular use cases or software applications. We describe the evolution of BAO related to its formal structures, engineering approaches, and content to enable modeling of complex assays and integration with other ontologies and datasets.

Background The diverse set of human brain structure and function analysis methods represents a difficult challenge for reconciling multiple views of neuroanatomical organization. While different views of organization are expected and valid, no widely adopted approach exists to harmonize different brain labeling protocols and terminologies. Our approach uses the natural organizing framework provided by anatomical structure to correlate terminologies commonly used in neuroimaging. Description The Foundational Model of Anatomy (FMA) Ontology provides a semantic framework for representing the anatomical entities and relationships that constitute the phenotypic organization of the human body. In this paper we describe recent enhancements to the neuroanatomical content of the FMA that models cytoarchitectural and morphological regions of the cerebral cortex, as well as white matter structure and connectivity. This modeling effort is driven by the need to correlate and reconcile the terms used in neuroanatomical labeling protocols. By providing an ontological framework that harmonizes multiple views of neuroanatomical organization, the FMA provides developers with reusable and computable knowledge for a range of biomedical applications. Conclusions A requirement for facilitating the integration of basic and clinical neuroscience data from diverse sources is a well-structured ontology that can incorporate, organize, and associate neuroanatomical data. We applied the ontological framework of the FMA to align the vocabularies used by several human brain atlases, and to encode emerging knowledge about structural connectivity in the brain. We highlighted several use cases of these extensions, including ontology reuse, neuroimaging data annotation, and organizing 3D brain models.

Background Genome sequencing of many eukaryotic pathogens and the volume of data available on public resources have created a clear requirement for a consistent vocabulary to describe the range of developmental forms of parasites. Consistent labeling of experimental data and external data, in databases and the literature, is essential for integration, cross database comparison, and knowledge discovery. The primary objective of this work was to develop a dynamic and controlled vocabulary that can be used for various parasites. The paper describes the Ontology for Parasite Lifecycle (OPL) and discusses its application in parasite research. Results The OPL is based on the Basic Formal Ontology (BFO) and follows the rules set by the OBO Foundry consortium. The first version of the OPL models complex life cycle stage details of a range of parasites, such as Trypanosoma sp., Leishmaniasp., Plasmodium sp., and Shicstosoma sp. In addition, the ontology also models necessary contextual details, such as host information, vector information, and anatomical locations. OPL is primarily designed to serve as a reference ontology for parasite life cycle stages that can be used for database annotation purposes and in the lab for data integration or information retrieval as exemplified in the application section below. Conclusion OPL is freely available at http://purl.obolibrary.org/obo/opl.owl and has been submitted to the BioPortal site of NCBO and to the OBO Foundry. We believe that database and phenotype annotations using OPL will help run fundamental queries on databases to know more about gene functions and to find intervention targets for various parasites. The OPL is under continuous development and new parasites and/or terms are being added.

Background Understanding the distinction between function and role is vexing and difficult. While it appears to be useful, in practice this distinction is hard to apply, particularly within biology. Results I take an evolutionary approach, considering a series of examples, to develop and generate definitions for these concepts. I test them in practice against the Ontology for Biomedical Investigations (OBI). Finally, I give an axiomatisation and discuss methods for applying these definitions in practice. Conclusions The definitions in this paper are applicable, formalizing current practice. As such, they make a significant contribution to the use of these concepts within biomedical ontologies.

Background Phenotypes form the basis for determining the existence of a disease against the given evidence. Much of this evidence though remains locked away in text – scientific articles, clinical trial reports and electronic patient records (EPR) – where authors use the full expressivity of human language to report their observations. Results In this paper we exploit a combination of off-the-shelf tools for extracting a machine understandable representation of phenotypes and other related concepts that concern the diagnosis and treatment of diseases. These are tested against a gold standard EPR collection that has been annotated with Unified Medical Language System (UMLS) concept identifiers: the ShARE/CLEF 2013 corpus for disorder detection. We evaluate four pipelines as stand-alone systems and then attempt to optimise semantic-type based performance using several learn-to-rank (LTR) approaches – three pairwise and one listwise. We observed that whilst overall Apache cTAKES tended to outperform other stand-alone systems on a strong recall (R = 0.57), precision was low (P = 0.09) leading to low-to-moderate F1 measure (F1 = 0.16). Moreover, there is substantial variation in system performance across semantic types for disorders. For example, the concept Findings (T033) seemed to be very challenging for all systems. Combining systems within LTR improved F1 substantially (F1 = 0.24) particularly for Disease or syndrome (T047) and Anatomical abnormality (T190). Whilst recall is improved markedly, precision remains a challenge (P = 0.15, R = 0.59).

Background Model repositories such as BioModels Database provide computational models of biological systems for the scientific community. These models contain rich semantic annotations that link model entities to concepts in well-established bio-ontologies such as Gene Ontology. Consequently, thematically similar models are likely to share similar annotations. Based on this assumption, we argue that semantic annotations are a suitable tool to characterize sets of models. These characteristics improve model classification, allow to identify additional features for model retrieval tasks, and enable the comparison of sets of models. Results In this paper we discuss four methods for annotation-based feature extraction from model sets. We tested all methods on sets of models in SBML format which were composed from BioModels Database. To characterize each of these sets, we analyzed and extracted concepts from three frequently used ontologies, namely Gene Ontology, ChEBI and SBO. We find that three out of the methods are suitable to determine characteristic features for arbitrary sets of models: The selected features vary depending on the underlying model set, and they are also specific to the chosen model set. We show that the identified features map on concepts that are higher up in the hierarchy of the ontologies than the concepts used for model annotations. Our analysis also reveals that the information content of concepts in ontologies and their usage for model annotation do not correlate. Conclusions Annotation-based feature extraction enables the comparison of model sets, as opposed to existing methods for model-to-keyword comparison, or model-to-model comparison. Electronic supplementary material The online version of this article (doi:10.1186/s13326-015-0014-4) contains supplementary material, which is available to authorized users.

Background: Semantic relatedness is a measure that quantifies the strength of a semantic link between two concepts. Often, it can be efficiently approximated with methods that operate on words, which represent these concepts. Approximating semantic relatedness between texts and concepts represented by these texts is an important part of many text and knowledge processing tasks of crucial importance in the ever growing domain of biomedical informatics. The problem of most state-of-the-art methods for calculating semantic relatedness is their dependence on highly specialized, structured knowledge resources, which makes these methods poorly adaptable for many usage scenarios. On the other hand, the domain knowledge in the Life Sciences has become more and more accessible, but mostly in its unstructured form - as texts in large document collections, which makes its use more challenging for automated processing. In this paper we present tESA, an extension to a well known Explicit Semantic Relatedness (ESA) method.Results: In our extension we use two separate sets of vectors, corresponding to different sections of the articles from the underlying corpus of documents, as opposed to the original method, which only uses a single vector space. We present an evaluation of Life Sciences domain-focused applicability of both tESA and domain-adapted Explicit Semantic Analysis. The methods are tested against a set of standard benchmarks established for the evaluation of biomedical semantic relatedness quality. Our experiments show that the propsed method achieves results comparable with or superior to the current state-of-the-art methods. Additionally, a comparative discussion of the results obtained with tESA and ESA is presented, together with a study of the adaptability of the methods to different corpora and their performance with different input parameters.Conclusions: Our findings suggest that combined use of the semantics from different sections (i.e. extending the original ESA methodology with the use of title vectors) of the documents of scientific corpora may be used to enhance the performance of a distributional semantic relatedness measures, which can be observed in the largest reference datasets. We also present the impact of the proposed extension on the size of distributional representations.

The “Vaccine and Drug Ontology Studies” (VDOS) international workshop series focuses on vaccine- and drug-related ontology modeling and applications. Drugs and vaccines have been critical to prevent and treat human and animal diseases. Work in both (drugs and vaccines) areas is closely related - from preclinical research and development to manufacturing, clinical trials, government approval and regulation, and post-licensure usage surveillance and monitoring. Over the last decade, tremendous efforts have been made in the biomedical ontology community to ontologically represent various areas associated with vaccines and drugs – extending existing clinical terminology systems such as SNOMED, RxNorm, NDF-RT, and MedDRA, developing new models such as the Vaccine Ontology (VO) and Ontology of Adverse Events (OAE), vernacular medical terminologies such as the Consumer Health Vocabulary (CHV). The VDOS workshop series provides a platform for discussing innovative solutions as well as the challenges in the development and applications of biomedical ontologies for representing and analyzing drugs and vaccines, their administration, host immune responses, adverse events, and other related topics. The five full-length papers included in this 2014 thematic issue focus on two main themes: (i) General vaccine/drug-related ontology development and exploration, and (ii) Interaction and network-related ontology studies.

Background Information about drug–drug interactions (DDIs) is crucial for computational applications such as pharmacovigilance and drug repurposing. However, existing sources of DDIs have the problems of low coverage, low accuracy and low agreement. One common type of DDIs is related to the mechanism of drug metabolism: a DDI relation may be caused by different interactions (e.g., substrate, inhibit) between drugs and enzymes in the drug metabolism process. Thus, information from drug enzyme interactions (DEIs) serves as important supportive evidence for DDIs. Further, potential DDIs present implicitly could be detected by inference and reasoning based on DEIs. Methods In this article, we propose a hybrid approach to combining machine learning algorithm with trigger words and syntactic patterns, for DEI relation extraction from biomedical literature. The extracted DEI relations are used for reasoning to infer potential DDI relations, based on a defined drug-enzyme ontology incorporating biological knowledge. Results Evaluation results demonstrate that the performance of DEI relation extraction is promising, with an F-measure of 84.97 % on the in vivo dataset and 65.58 % on the in vitro dataset. Further, the inferred DDIs achieved a precision of 83.19 % on the in vivo dataset and 70.94 % on the in vitro dataset, respectively. A further examination showed that the overlaps between our inferred DDIs and those present in DrugBank were 42.02 % on the in vivo dataset and 19.23 % on the in vitro dataset, respectively. Conclusions This paper proposed an effective approach to extract DEI relations from biomedical literature. Potential DDIs not present in existing knowledge bases were then inferred based on the extracted DEIs, demonstrating the capability of the proposed approach to detect DDIs with scientific evidence for pharmacovigilance and drug repurposing applications.

Background Vaccines are one of the most important public health successes in last century. Besides effectiveness in reducing the morbidity and mortality from many infectious diseases, a successful vaccine program also requires a rigorous assessment on their safety. Due to the limitations of adverse event (AE) data from clinical trials and post-approval surveillance systems, novel computational approaches are needed to organize, visualize, and analyze such high-dimensional complex data. Results In this paper, we proposed a network-based approach to investigate the vaccine-AE association network from the Vaccine AE Reporting System (VAERS) data. Statistical summary was calculated using the VAERS raw data and represented in the Resource Description Framework (RDF). The RDF graph was leveraged for network analysis. Specifically, we compared network properties of (1) vaccine - adverse event association network based on reports collected over a 23 year period as well as each year; and (2) sex-specific vaccine-adverse event association network. We observed that (1) network diameter and average path length don’t change dramatically over a 23-year period, while the average node degree of these networks changes due to the different number of reports during different periods of time; (2) vaccine - adverse event associations derived from different sexes show sex-associated patterns in sex-specific vaccine-AE association networks. Conclusions We have developed a network-based approach to investigate the vaccine-AE association network from the VAERS data. To our knowledge, this is the first time that a network-based approach was used to identify sex-specific association patterns in a spontaneous reporting system database. Due to unique limitations of such passive surveillance systems, our proposed network-based approaches have the potential to summarize and analyze the associations in passive surveillance systems by (1) identifying nodes of importance, irrespective of whether they are disproportionally reported; (2) providing guidance on sex-specific recommendations in personalized vaccinology. Electronic supplementary material The online version of this article (doi:10.1186/s13326-015-0032-2) contains supplementary material, which is available to authorized users.

Background The Simple Knowledge Organization System (SKOS) was introduced to the wider research community by a 2005 World Wide Web Consortium (W3C) working draft, and further developed and refined in a 2009 W3C recommendation. Since then, SKOS has become the de facto standard for representing and sharing thesauri, lexicons, vocabularies, taxonomies, and classification schemes. In this paper, we describe the development of a web-based, free, open-source SKOS editor built for the development, curation, and management of small to medium-sized lexicons for health-related Natural Language Processing (NLP). Results The web-based SKOS editor allows users to create, curate, version, manage, and visualise SKOS resources. We tested the system against five widely-used, publicly-available SKOS vocabularies of various sizes and found that the editor is suitable for the development and management of small to medium-size lexicons. Qualitative testing has focussed on using the editor to develop lexical resources to drive NLP applications in two domains. First, developing a lexicon to support an Electronic Health Record-based NLP system for the automatic identification of pneumonia symptoms. Second, creating a taxonomy of lexical cues associated with Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnoses with the goal of facilitating the automatic identification of symptoms associated with depression from short, informal texts. Conclusions The SKOS editor we have developed is — to the best of our knowledge — the first free, open-source, web-based, SKOS editor capable of creating, curating, versioning, managing, and visualising SKOS lexicons. Electronic supplementary material The online version of this article (doi:10.1186/s13326-015-0043-z) contains supplementary material, which is available to authorized users.

This paper presents a new approach to exploit coreference information for extracting event-argument (E-A) relations from biomedical documents. This approach has two advantages: (1) it can extract a large number of valuable E-A relations based on the concept of salience in discourse; (2) it enables us to identify E-A relations over sentence boundaries (cross-links) using transitivity of coreference relations. We propose two coreference-based models: a pipeline based on Support Vector Machine (SVM) classifiers, and a joint Markov Logic Network (MLN). We show the effectiveness of these models on a biomedical event corpus. Both models outperform the systems that do not use coreference information. When the two proposed models are compared to each other, joint MLN outperforms pipeline SVM with gold coreference information.

The 2013 “Vaccine and Drug Ontology Studies” (VDOS 2013) international workshop series focuses on vaccine- and drug-related ontology modeling and applications. Drugs and vaccines have contributed to dramatic improvements in public health worldwide. Over the last decade, tremendous efforts have been made in the biomedical ontology community to ontologically represent various areas associated with vaccines and drugs – extending existing clinical terminology systems such as SNOMED, RxNorm, NDF-RT, and MedDRA, as well as developing new models such as Vaccine Ontology. The VDOS workshop series provides a platform for discussing innovative solutions as well as the challenges in the development and applications of biomedical ontologies for representing and analyzing drugs and vaccines, their administration, host immune responses, adverse events, and other related topics. The six full-length papers included in this thematic issue focuses on three main areas: (i) ontology development and representation, (ii) ontology mapping, maintaining and auditing, and (iii) ontology applications.

Background In biomedical ontologies, mereological relations have always been subject to special interest due to their high relevance in structural descriptions of anatomical entities, cells, and biomolecules. This paper investigates two important subrelations of has_proper_part, viz. the relation has_grain, which relates a collective entity to its multiply occurring uniform parts (e.g., water molecules in a portion of water), and the relation has_component, which relates a compound to its constituents (e.g., molecules to the atoms they consist of). Method We distinguish between four kinds of complex entities and characterize them in first order logic. We then discuss whether similar characterizations could be given in description logics, and finally apply the results to mixtures. Results At first sight, collectives and compounds seem to be disjoint categories. Their disjointness, however, relies on agreement about what are uniform entities, and thus on the granularity of description. For instance, the distinction between isomeric subtypes of a molecule can be important in one use case but might be neglected in another one. We demonstrate that, as implemented in the BioTop domain upper level ontology, equivalence or subsumption between different descriptions of same or similar entities cannot be achieved. Using OWL-DL, we propose a new design pattern that avoids primitive subrelations at the expense of more complex descriptions and thus supports the needed inferences.

Contains fulltext : 125465.pdf (Publisher’s version ) (Open Access) BACKGROUND: The increasing amount of textual information in biomedicine requires effective term recognition methods to identify textual representations of domain-specific concepts as the first step toward automating its semantic interpretation. The dictionary look-up approaches may not always be suitable for dynamic domains such as biomedicine or the newly emerging types of media such as patient blogs, the main obstacles being the use of non-standardised terminology and high degree of term variation. RESULTS: In this paper, we describe FlexiTerm, a method for automatic term recognition from a domain-specific corpus, and evaluate its performance against five manually annotated corpora. FlexiTerm performs term recognition in two steps: linguistic filtering is used to select term candidates followed by calculation of termhood, a frequency-based measure used as evidence to qualify a candidate as a term. In order to improve the quality of termhood calculation, which may be affected by the term variation phenomena, FlexiTerm uses a range of methods to neutralise the main sources of variation in biomedical terms. It manages syntactic variation by processing candidates using a bag-of-words approach. Orthographic and morphological variations are dealt with using stemming in combination with lexical and phonetic similarity measures. The method was evaluated on five biomedical corpora. The highest values for precision (94.56%), recall (71.31%) and F-measure (81.31%) were achieved on a corpus of clinical notes. CONCLUSIONS: FlexiTerm is an open-source software tool for automatic term recognition. It incorporates a simple term variant normalisation method. The method proved to be more robust than the baseline against less formally structured texts, such as those found in patient blogs or medical notes. The software can be downloaded freely at http://www.cs.cf.ac.uk/flexiterm.

Background The treatment of negation and hedging in natural language processing has received much interest recently, especially in the biomedical domain. However, open access corpora annotated for negation and/or speculation are hardly available for training and testing applications, and even if they are, they sometimes follow different design principles. In this paper, the annotation principles of the two largest corpora containing annotation for negation and speculation – BioScope and Genia Event – are compared. BioScope marks linguistic cues and their scopes for negation and hedging while in Genia biological events are marked for uncertainty and/or negation. Results Differences among the annotations of the two corpora are thematically categorized and the frequency of each category is estimated. We found that the largest amount of differences is due to the issue that scopes – which cover text spans – deal with the key events and each argument (including events within events) of these events is under the scope as well. In contrast, Genia deals with the modality of events within events independently. Conclusions The analysis of multiple layers of annotation (linguistic scopes and biological events) showed that the detection of negation/hedge keywords and their scopes can contribute to determining the modality of key events (denoted by the main predicate). On the other hand, for the detection of the negation and speculation status of events within events, additional syntax-based rules investigating the dependency path between the modality cue and the event cue have to be employed.

The concept of a mechanism has become a standard proposal for explanations in biology. It has been claimed that mechanistic explanations are appropriate for systems biology, because they occupy a middle ground between strict reductionism and holism. Because of their importance in the field a formal ontological description of mechanisms is desirable. The standard philosophical accounts of mechanisms are often ambiguous and lack the clarity that can be provided by a formal-ontological framework. The goal of this paper is to clarify some of these ambiguities and suggest such a framework for mechanisms. Taking some hints from an "ontology of devices" I suggest as a general approach for this task the introduction of functional kinds and functional parts by which the particular relations between a mechanism and its components can be captured.

Clustering textual contents is an important step in mining useful information on the web or other text-based resources. The common task in text clustering is to handle text in a multi-dimensional space, and to partition documents into groups, where each group contains documents that are similar to each other. However, this strategy lacks a comprehensive view for humans in general since it cannot explain the main subject of each cluster. Utilizing semantic information can solve this problem, but it needs a well-defined ontology or pre-labeled gold standard set. In this paper, we present a thematic clustering algorithm for text documents. Given text, subject terms are extracted and used for clustering documents in a probabilistic framework. An EM approach is used to ensure documents are assigned to correct subjects, hence it converges to a locally optimal solution. The proposed method is distinctive because its results are sufficiently explanatory for human understanding as well as efficient for clustering performance. The experimental results show that the proposed method provides a competitive performance compared to other state-of-the-art approaches. We also show that the extracted themes from the MEDLINE® dataset represent the subjects of clusters reasonably well.