Desiderata for domain reference ontologies in biomedicine

Domain reference ontologies represent knowledge about a particular part of the world in a way that is independent from specific objectives, through a theory of the domain. An example of reference ontology in biomedical informatics is the Foundational Model of Anatomy (FMA), an ontology of anatomy that covers the entire range of macroscopic, microscopic, and subcellular anatomy. The purpose of this paper is to explore how two domain reference ontologies--the FMA and the Chemical Entities of Biological Interest (ChEBI) ontology, can be used (i) to align existing terminologies, (ii) to infer new knowledge in ontologies of more complex entities, and (iii) to manage and help reasoning about individual data. We analyze those kinds of usages of these two domain reference ontologies and suggest desiderata for reference ontologies in biomedicine. While a number of groups and communities have investigated general requirements for ontology design and desiderata for controlled medical vocabularies, we are focusing on application purposes. We suggest five desirable characteristics for reference ontologies: good lexical coverage, good coverage in terms of relations, compatibility with standards, modularity, and ability to represent variation in reality.     

A formal theory for spatial representation and reasoning in biomedical ontologies

OBJECTIVE: The objective of this paper is to demonstrate how a formal spatial theory can be used as an important tool for disambiguating the spatial information embodied in biomedical ontologies and for enhancing their automatic reasoning capabilities. METHOD AND MATERIALS: This paper presents a formal theory of parthood and location relations among individuals, called Basic Inclusion Theory (BIT). Since biomedical ontologies are comprised of assertions about classes of individuals (rather than assertions about individuals), we define parthood and location relations among classes in the extended theory Basic Inclusion Theory for Classes (BIT+Cl). We then demonstrate the usefulness of this formal theory for making the logical structure of spatial information more precise in two ontologies concerned with human anatomy: the Foundational Model of Anatomy (FMA) and GALEN. RESULTS: We find that in both the FMA and GALEN, class-level spatial relations with different logical properties are not always explicitly distinguished. As a result, the spatial information included in these biomedical ontologies is often ambiguous and the possibilities for implementing consistent automatic reasoning within or across ontologies are limited. CONCLUSION: Precise formal characterizations of all spatial relations assumed by a biomedical ontology are necessary to ensure that the information embodied in the ontology can be fully and coherently utilized in a computational environment. This paper can be seen as an important beginning step toward achieving this goal, but much more work along these lines is required.     

面向精准医学的生物医学本体资源存储和应用平台

在过去10余年中,本体广泛应用于生物医学数据分析、检索、整合和再利用中。本体作为一种特殊类型的数据资源,数据量也在迅速增加。为了促进精准医疗领域数据集的整合,并为国内用户提供本体数据资源服务,构建MedPortal本体资源存储和应用平台。通过复用NCBO BioPortal技术,搭建MedPotal软件框架。遴选精准医学相关本体,建立本体资源库。对原框架中的代码和本体处理工具进行修正和完善,使之能够在本体稳定运行的基础上满足大批量数据的自动化处理。目前,该平台已整合42个生物医学本体,建立了本体之间术语映射关系,通过页面和REST API方式,提供术语检索、本体映射、数据标准化注释等本体应用服务(http://medportal.bmicc.cn)。MedPortal本体平台将为生物医学数据整合提供帮助。     

Cross-domain targeted ontology subsets for annotation: The case of SNOMED CORE and RxNorm

The benefits of using ontology subsets versus full ontologies are well-documented for many applications. In this study, we propose an efficient subset extraction approach for a domain using a biomedical ontology repository with mappings, a cross-ontology, and a source subset from a related domain. As a case study, we extracted a subset of drugs from RxNorm using the UMLS Metathesaurus, the NDF-RT cross-ontology, and the CORE problem list subset of SNOMED CT. The extracted subset, which we termed RxNorm/CORE, was 4% the size of the full RxNorm (0.4% when considering ingredients only). For evaluation, we used CORE and RxNorm/CORE as thesauri for the annotation of clinical documents and compared their performance to that of their respective full ontologies (i.e., SNOMED CT and RxNorm). The wide range in recall of both CORE (29–69%) and RxNorm/CORE (21–35%) suggests that more quantitative research is needed to assess the benefits of using ontology subsets as thesauri in annotation applications. Our approach to subset extraction, however, opens a door to help create other types of clinically useful domain specific subsets and acts as an alternative in scenarios where well-established subset extraction techniques might suffer from difficulties or cannot be applied.     

Summarizing and visualizing structural changes during the evolution of biomedical ontologies using a Diff Abstraction Network

Biomedical ontologies are a critical component in biomedical research and practice. As an ontology evolves, its structure and content change in response to additions, deletions and updates. When editing a biomedical ontology, small local updates may affect large portions of the ontology, leading to unintended and potentially erroneous changes. Such unwanted side effects often go unnoticed since biomedical ontologies are large and complex knowledge structures. Abstraction networks, which provide compact summaries of an ontology’s content and structure, have been used to uncover structural irregularities, inconsistencies and errors in ontologies. In this paper, we introduce Diff Abstraction Networks (“Diff AbNs”), compact networks that summarize and visualize global structural changes due to ontology editing operations that result in a new ontology release. A Diff AbN can be used to support curators in identifying unintended and unwanted ontology changes. The derivation of two Diff AbNs, the Diff Area Taxonomy and the Diff Partial-area Taxonomy, is explained and Diff Partial-area Taxonomies are derived and analyzed for the Ontology of Clinical Research, Sleep Domain Ontology, and eagle-i Research Resource Ontology. Diff Taxonomy usage for identifying unintended erroneous consequences of quality assurance and ontology merging are demonstrated.     

A reference ontology for biomedical informatics: the Foundational Model of Anatomy

The Foundational Model of Anatomy (FMA), initially developed as an enhancement of the anatomical content of UMLS, is a domain ontology of the concepts and relationships that pertain to the structural organization of the human body. It encompasses the material objects from the molecular to the macroscopic levels that constitute the body and associates with them non-material entities (spaces, surfaces, lines, and points) required for describing structural relationships. The disciplined modeling approach employed for the development of the FMA relies on a set of declared principles, high level schemes, Aristotelian definitions and a frame-based authoring environment. We propose the FMA as a reference ontology in biomedical informatics for correlating different views of anatomy, aligning existing and emerging ontologies in bioinformatics ontologies and providing a structure-based template for representing biological functions.     

A multi-ontology approach to annotate scientific documents based on a modularization technique

Scientific text annotation has become an important task for biomedical scientists. Nowadays, there is an increasing need for the development of intelligent systems to support new scientific findings. Public databases available on the Web provide useful data, but much more useful information is only accessible in scientific texts. Text annotation may help as it relies on the use of ontologies to maintain annotations based on a uniform vocabulary. However, it is difficult to use an ontology, especially those that cover a large domain. In addition, since scientific texts explore multiple domains, which are covered by distinct ontologies, it becomes even more difficult to deal with such task. Moreover, there are dozens of ontologies in the biomedical area, and they are usually big in terms of the number of concepts. It is in this context that ontology modularization can be useful. This work presents an approach to annotate scientific documents using modules of different ontologies, which are built according to a module extraction technique. The main idea is to analyze a set of single-ontology annotations on a text to find out the user interests. Based on these annotations a set of modules are extracted from a set of distinct ontologies, and are made available for the user, for complementary annotation. The reduced size and focus of the extracted modules tend to facilitate the annotation task. An experiment was conducted to evaluate this approach, with the participation of a bioinformatician specialist of the Laboratory of Peptides and Proteins of the IOC/Fiocruz, who was interested in discovering new drug targets aiming at the combat of tropical diseases.     

Discovering Beaten Paths in Collaborative Ontology-Engineering Projects using Markov Chains

Biomedical taxonomies, thesauri and ontologies in the form of the International Classification of Diseases as a taxonomy or the National Cancer Institute Thesaurus as an OWL-based ontology, play a critical role in acquiring, representing and processing information about human health. With increasing adoption and relevance, biomedical ontologies have also significantly increased in size. For example, the 11th revision of the International Classification of Diseases, which is currently under active development by the World Health Organization contains nearly $50\text{,}000$ classes representing a vast variety of different diseases and causes of death. This evolution in terms of size was accompanied by an evolution in the way ontologies are engineered. Because no single individual has the expertise to develop such large-scale ontologies, ontology-engineering projects have evolved from small-scale efforts involving just a few domain experts to large-scale projects that require effective collaboration between dozens or even hundreds of experts, practitioners and other stakeholders. Understanding the way these different stakeholders collaborate will enable us to improve editing environments that support such collaborations. In this paper, we uncover how large ontology-engineering projects, such as the International Classification of Diseases in its 11th revision, unfold by analyzing usage logs of five different biomedical ontology-engineering projects of varying sizes and scopes using Markov chains. We discover intriguing interaction patterns (e.g., which properties users frequently change after specific given ones) that suggest that large collaborative ontology-engineering projects are governed by a few general principles that determine and drive development. From our analysis, we identify commonalities and differences between different projects that have implications for project managers, ontology editors, developers and contributors working on collaborative ontology-engineering projects and tools in the biomedical domain.     

A novel approach for connecting temporal-ontologies with blood flow simulations

In this paper an approach for developing a temporal domain ontology for biomedical simulations is introduced. The ideas are presented in the context of simulations of blood flow in aneurysms using the Lattice Boltzmann Method. The advantages in using ontologies are manyfold: On the one hand, ontologies having been proven to be able to provide medical special knowledge e.g., key parameters for simulations. On the other hand, based on a set of rules and the usage of a reasoner, a system for checking the plausibility as well as tracking the outcome of medical simulations can be constructed. Likewise, results of simulations including data derived from them can be stored and communicated in a way that can be understood by computers. Later on, this set of results can be analyzed. At the same time, the ontologies provide a way to exchange knowledge between researchers. Lastly, this approach can be seen as a black-box abstraction of the internals of the simulation for the biomedical researcher as well. This approach is able to provide the complete parameter sets for simulations, part of the corresponding results and part of their analysis as well as e.g., geometry and boundary conditions. These inputs can be transferred to different simulation methods for comparison. Variations on the provided parameters can be automatically used to drive these simulations. Using a rule base, unphysical inputs or outputs of the simulation can be detected and communicated to the physician in a suitable and familiar way. An example for an instantiation of the blood flow simulation ontology and exemplary rules for plausibility checking are given.     

ApiNATOMY: a novel toolkit for visualizing multiscale anatomy schematics with phenotype-related information

A significant proportion of biomedical resources carries information that cross references to anatomical structures across multiple scales. To improve the visualization of such resources in their anatomical context, we developed an automated methodology that produces anatomy schematics in a consistent manner,and provides for the overlay of anatomy-related resource information onto the same diagram. This methodology, called ApiNATOMY, draws upon the topology of ontology graphs to automatically lay out treemaps representing body parts as well as semantic metadata linking to such ontologies. More generally, ApiNATOMY treemaps provide an efficient and manageable way to visualize large biomedical ontologies in a meaningful and consistent manner. In the anatomy domain, such treemaps will allow epidemiologists, clinicians, and biomedical scientists to review, and interact with, anatomically aggregated heterogeneous data and model resources. Such an approach supports the visual identification of functional relations between anatomically colocalized resources that may not be immediately amenable to automation by ontology-based inferencing. We also describe the application of ApiNATOMY schematics to integrate, and add value to, human phenotype-related information—results are found at http://apinatomy.org. The long-term goal for the ApiNATOMY toolkit is to support clinical and scientific graphical user interfaces and dashboards for biomedical resource management and data analytics.     

Biomedical Ontologies to Guide AI Development in Radiology

The advent of deep learning has engendered renewed and rapidly growing interest in artificial intelligence (AI) in radiology to analyze images, manipulate textual reports, and plan interventions. Applications of deep learning and other AI approaches must be guided by sound medical knowledge to assure that they are developed successfully and that they address important problems in biomedical research or patient care. To date, AI has been applied to a limited number of real-world radiology applications. As AI systems become more pervasive and are applied more broadly, they will benefit from medical knowledge on a larger scale, such as that available through computer-based approaches. A key approach to represent computer-based knowledge in a particular domain is an ontology. As defined in informatics, an ontology defines a domain’s terms through their relationships with other terms in the ontology. Those relationships, then, define the terms’ semantics, or “meaning.” Biomedical ontologies commonly define the relationships between terms and more general terms, and can express causal, part-whole, and anatomic relationships. Ontologies express knowledge in a form that is both human-readable and machine-computable. Some ontologies, such as RSNA’s RadLex radiology lexicon, have been applied to applications in clinical practice and research, and may be familiar to many radiologists. This article describes how ontologies can support research and guide emerging applications of AI in radiology, including natural language processing, image–based machine learning, radiomics, and planning.

     

An ontology of randomized controlled trials for evidence-based practice: content specification and evaluation using the competency decomposition method

Randomized controlled trials (RCTs) are one of the least biased sources of clinical research evidence, and are therefore a critical resource for the practice of evidence-based medicine. With over 10,000 new RCTs indexed in Medline each year, knowledge systems are needed to help clinicians translate evidence into practice. Common ontologies for RCTs and other domains would facilitate the development of these knowledge systems. However, no standard method exists for developing domain ontologies. In this paper, we describe a new systematic approach to specifying and evaluating the conceptual content of ontologies. In this method, called competency decomposition, the target task for an ontology is hierarchically decomposed into subtasks and methods, and the ontology content is specified by identifying the domain information required to complete each of the subtasks. We illustrate the use of this competency decomposition approach for the content specification and evaluation of an RCT ontology for evidence-based practice.     

Text-mining approach to evaluate terms for ontology development

Developing ontologies to account for the complexity of biological systems requires the time intensive collaboration of many participants with expertise in various fields. While each participant may contribute to construct a list of terms for ontology development, no objective methods have been developed to evaluate how relevant each of these terms is to the intended domain. We have developed a computational method based on a hypergeometric enrichment test to evaluate the relevance of such terms to the intended domain. The proposed method uses the PubMed literature database to evaluate whether each potential term for ontology development is overrepresented in the abstracts that discuss the particular domain. This evaluation provides an objective approach to assess terms and prioritize them for ontology development.     

BOAT: automatic alignment of biomedical ontologies using term informativeness and candidate selection

The biomedical sciences is one of the few domains where ontologies are widely being developed to facilitate information retrieval and knowledge sharing, but there still remains the problem that applications using different ontologies cannot share knowledge without explicit references between overlapping concepts. Ontology alignment is the task of identifying such equivalence relations between concepts across ontologies. Its application to the biomedical domain should address two open issues: (1) determining the equivalence of concept-pairs which have overlapping terms in their names, and (2) the high run-time required to align large ontologies which are typical in the biomedical domain. To address them, we present a novel approach, named the Biomedical Ontologies Alignment Technique (BOAT), which is state-of-the-art in terms of F-measure, precision and speed. A key feature of BOAT is that it considers the informativeness of each component word in the concept labels, which has significant impact on biomedical ontologies, resulting in a 12.2% increase in F-measure. Another important feature of BOAT is that it selects for comparison only concept pairs that show high likelihoods of equivalence, based on the similarity of their annotations. BOAT's F-measure of 0.88 for the alignment of the mouse and human anatomy ontologies is on par with that of another state-of-the-art matcher, AgreementMaker, while taking a shorter time.     

An empirical analysis of ontology reuse in BioPortal

Biomedical ontologies often reuse content (i.e., classes and properties) from other ontologies. Content reuse enables a consistent representation of a domain and reusing content can save an ontology author significant time and effort. Prior studies have investigated the existence of reused terms among the ontologies in the NCBO BioPortal, but as of yet there has not been a study investigating how the ontologies in BioPortal utilize reused content in the modeling of their own content. In this study we investigate how 355 ontologies hosted in the NCBO BioPortal reuse content from other ontologies for the purposes of creating new ontology content. We identified 197 ontologies that reuse content. Among these ontologies, 108 utilize reused classes in the modeling of their own classes and 116 utilize reused properties in class restrictions. Current utilization of reuse and quality issues related to reuse are discussed.     

Dynamic sub-ontology evolution for traditional Chinese medicine web ontology

As a form of important domain knowledge, large-scale ontologies play a critical role in building a large variety of knowledge-based systems. To overcome the problem of semantic heterogeneity and encode domain knowledge in reusable format, a large-scale and well-defined ontology is also required in the traditional Chinese medicine discipline. We argue that to meet the on-demand and scalability requirement ontology-based systems should go beyond the use of static ontology and be able to self-evolve and specialize for the domain knowledge they possess. In particular, we refer to the context-specific portions from large-scale ontologies like the traditional Chinese medicine ontology as sub-ontologies. Ontology-based systems are able to reuse sub-ontologies in local repository called ontology cache. In order to improve the overall performance of ontology cache, we propose to evolve sub-ontologies in ontology cache to optimize the knowledge structure of sub-ontologies. Moreover, we present the sub-ontology evolution approach based on a genetic algorithm for reusing large-scale ontologies. We evaluate the proposed evolution approach with the traditional Chinese medicine ontology and obtain promising results.     

Semantic enrichment for medical ontologies

The Unified Medical Language System (UMLS) contains two separate but interconnected knowledge structures, the Semantic Network (upper level) and the Metathesaurus (lower level). In this paper, we have attempted to work out better how the use of such a two-level structure in the medical field has led to notable advances in terminologies and ontologies. However, most ontologies and terminologies do not have such a two-level structure. Therefore, we present a method, called semantic enrichment, which generates a two-level ontology from a given one-level terminology and an auxiliary two-level ontology. During semantic enrichment, concepts of the one-level terminology are assigned to semantic types, which are the building blocks of the upper level of the auxiliary two-level ontology. The result of this process is the desired new two-level ontology. We discuss semantic enrichment of two example terminologies and how we approach the implementation of semantic enrichment in the medical domain. This implementation performs a major part of the semantic enrichment process with the medical terminologies, with difficult cases left to a human expert.     

GOClonto: An ontological clustering approach for conceptualizing PubMed abstracts

Concurrent with progress in biomedical sciences, an overwhelming of textual knowledge is accumulating in the biomedical literature. PubMed is the most comprehensive database collecting and managing biomedical literature. To help researchers easily understand collections of PubMed abstracts, numerous clustering methods have been proposed to group similar abstracts based on their shared features. However, most of these methods do not explore the semantic relationships among groupings of documents, which could help better illuminate the groupings of PubMed abstracts. To address this issue, we proposed an ontological clustering method called GOClonto for conceptualizing PubMed abstracts. GOClonto uses latent semantic analysis (LSA) and gene ontology (GO) to identify key gene-related concepts and their relationships as well as allocate PubMed abstracts based on these key gene-related concepts. Based on two PubMed abstract collections, the experimental results show that GOClonto is able to identify key gene-related concepts and outperforms the STC (suffix tree clustering) algorithm, the Lingo algorithm, the Fuzzy Ants algorithm, and the clustering based TRS (tolerance rough set) algorithm. Moreover, the two ontologies generated by GOClonto show significant informative conceptual structures.     

COnto–Diff: generation of complex evolution mappings for life science ontologies

Life science ontologies evolve frequently to meet new requirements or to better reflect the current domain knowledge. The development and adaptation of large and complex ontologies is typically performed collaboratively by several curators. To effectively manage the evolution of ontologies it is essential to identify the difference (Diff) between ontology versions. Such a Diff supports the synchronization of changes in collaborative curation, the adaptation of dependent data such as annotations, and ontology version management. We propose a novel approach COnto–Diff to determine an expressive and invertible diff evolution mapping between given versions of an ontology. Our approach first matches the ontology versions and determines an initial evolution mapping consisting of basic change operations (insert/update/delete). To semantically enrich the evolution mapping we adopt a rule-based approach to transform the basic change operations into a smaller set of more complex change operations, such as merge, split, or changes of entire subgraphs. The proposed algorithm is customizable in different ways to meet the requirements of diverse ontologies and application scenarios. We evaluate the proposed approach for large life science ontologies including the Gene Ontology and the NCI Thesaurus and compare it with PromptDiff. We further show how the Diff results can be used for version management and annotation migration in collaborative curation.