Barry Smith

We present some ideas on logical process descriptions, using relations from the DIO (Drug Interaction Ontology) as examples and explaining how these relations can be naturally decomposed in terms of more basic structured logical process descriptions using terms from linear logic. In our view, the process descriptions are able to clarify the usual relational descriptions of DIO. In particular, we discuss the use of logical process descriptions in proving linear logical theorems. Among the types of reasoning supported by DIO one can distinguish both (1) basic reasoning about general structures in reality and (2) the domain-specific reasoning of experts. We here propose a clarification of this important distinction between (realist) reasoning on the basis of an ontology and rule-based inferences on the basis of an expert’s view.

The central hypothesis of the collaboration between Language and Computing (L&C) and the Institute for Formal Ontology and Medical Information Science (IFOMIS) is that the methodology and conceptual rigor of a philosophically inspired formal ontology greatly benefits application ontologies.[1] To this end LinKBase®, L&C’s ontology, which is designed to integrate and reason across various external databases simultaneously, has been submitted to the conceptual demands of IFOMIS’s Basic Formal Ontology (BFO).[2] With this project we aim to move beyond the level of controlled vocabularies to yield an ontology with the ability to support reasoning applications. Our general procedure has been the implementation of a meta-ontological definition space in which the definitions of all the concepts and relations in LinKBase® are standardized in a framework of first-order logic. In this paper we describe how this standardization has already led to an improvement in the LinKBase® structure that allows for a greater degree of internal coherence than ever before possible. We then show the use of this philosophical standardization for the purpose of mapping external databases to one another, using LinKBase® as translation hub, with a greater degree of success than possible hitherto. We demonstrate how this offers a genuine advance over other application ontologies that have not submitted themselves to the demands of philosophical scrutiny.

The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates to UniProtKB in that PRO’s organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO’s representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments.

Referent tracking (RT) is a new paradigm, based on unique identification, for representing and keeping track of particulars. It was first introduced to support the entry and retrieval of data in electronic health records (EHRs). Its purpose is to avoid the ambiguity that arises when statements in an EHR refer to disorders or other entities on the side of the patient exclusively by means of compound descriptions utilizing general terms such as ‘pimple on nose’ or ‘small left breast tumor’. In this paper, we describe the theoretical foundations of this paradigm and show how it is being applied to the solution of analogous problems of ambiguous identification in the fields of digital rights management, corporate memories and decision algorithms.

The Protein Ontology (PRO) web resource provides an integrative framework for protein-centric exploration and enables specific and precise annotation of proteins and protein complexes based on PRO. Functionalities include: browsing, searching and retrieving, terms, displaying selected terms in OBO or OWL format, and supporting URIs. In addition, the PRO website offers multiple ways for the user to request, submit, or modify terms and/or annotation. We will demonstrate the use of these tools for protein research and annotation.

The most obvious varieties of mental phenomena directed to non- existent objects occur in our experiences of works of art. The task of applying the Meinongian ontology of the non-existent to the working out of a theory of aesthetic phenomena was however carried out not by Meinong by his disciple Stephan Witasek in his Grundzüge der allgemeinen Ästhetik of 1904. Witasek shows in detail how our feelings undergo certain sorts of structural modifications when they are directed towards what does not exist. He draws a distinction between genuine mental phenomena and what he calls `phantasy-material', asserting that `the job of the aesthetic object, whether it is a work of art or a product of nature, is to excite and support the actualisation of phantasy-material in the experiencing subject'. We might think of such phantasy-material as a matter of Ersatz-emotions or emotional `slop'. We could then see Witasek's aesthetics as an elaborate taxonomy of the various different sorts of Ersatz-emotions which the subject allows to be stimulated within himself in his intercourse with works of art, and see works of art themselves as machines for the production of ever more subtle varieties of such phantasy-material in the perceiving subject.

The paper challenges the assumption, common amongst philosophers, that the reality described in the fundamental theories of microphysics is all the reality we have. It will be argued that this assumption is in fact incompatible with the nature of such theories. It will be shown further that the macro-world of three-dimensional bodies and of such qualitative structures as colour and sound can be treated scientifically on its own terms, which is to say not only from the perspective of psychology but also ontologically. A new sort of emergentist position will be defended, one which yields the basis of a method for describing the perceptually salient macroscopic world in mathematical terms. Broadly, it will be argued that the macroscopic world exists in virtue of certain specific sorts of boundary-patterns in the field of what is captured by the theories of microphysics.

According to the PubMed resource from the U.S. National Library of Medicine, over 750,000 scientific articles have been published in the ~5000 biomedical journals worldwide in the year 2007 alone. The vast majority of these publications include results from hypothesis-driven experimentation in overlapping biomedical research domains. Unfortunately, the sheer volume of information being generated by the biomedical research enterprise has made it virtually impossible for investigators to stay aware of the latest findings in their domain of interest, let alone to be able to assimilate and mine data from related investigations for purposes of meta-analysis. While computers have the potential for assisting investigators in the extraction, management and analysis of these data, information contained in the traditional journal publication is still largely unstructured, free-text descriptions of study design, experimental application and results interpretation, making it difficult for computers to gain access to the content of what is being conveyed without significant manual intervention. In order to circumvent these roadblocks and make the most of the output from the biomedical research enterprise, a variety of related standards in knowledge representation are being developed, proposed and adopted in the biomedical community. In this chapter, we will explore the current status of efforts to develop minimum information standards for the representation of a biomedical experiment, ontologies composed of shared vocabularies assembled into subsumption hierarchical structures, and extensible relational data models that link the information components together in a machine-readable and human-useable framework for data mining purposes.

The theory of granular partitions (TGP) is a new approach to the understanding of ontologies and other classificatory systems. The paper explores the use of this new theory in the treatment of task-based clinical guidelines as a means for better understanding the relations between different clinical tasks, both within the framework of a single guideline and between related guidelines. We used as our starting point a DAML+OIL-based ontology for the WHO guideline for hypertension management, comparing this with related guidelines and attempting to show that TGP provides a flexible and highly expressive basis for the manipulation of ontologies of a sort which might be useful in providing more adequate Computer Interpretable Guideline Models (CIGMs) in the future.

Successful biomedical data mining and information extraction require a complete picture of biological phenomena such as genes, biological processes, and diseases; as these exist on different levels of granularity. To realize this goal, several freely available heterogeneous databases as well as proprietary structured datasets have to be integrated into a single global customizable scheme. We will present a tool to integrate different biological data sources by mapping them to a proprietary biomedical ontology that has been developed for the purposes of making computers understand medical natural language.

Information may be defined as the conceptual or communicable part of the content of mental acts. The content of mental acts includes sensory data as well as concepts, particular as well as general information. An information system is an external (non-mental) system designed to store such content. Information systems afford indirect transmission of content between people, some of whom may put information into the system and others who are among those who use the system. In order for communication to happen, the conceptual systems of the originators and users of the information must be sufficiently similar. A formal conceptual framework that can provide the basis for exchange of information is termed an ontology. In its most fundamental form, ontology studies the most basic constituents of reality. Traditionally, ontology seeks to reflects structures that are independent of thought and cognition. The term ontology is used more broadly in artificial intelligence and software engineering, to refer to the conceptual basis for an information system.

Representing the kinetic state of a patient (posture, motion, and activity) during vital sign measurement is an important part of continuous monitoring applications, especially remote monitoring applications. In contextualized vital sign representation, the measurement result is presented in conjunction with salient measurement context metadata. We present an automated annotation system for vital sign measurements that uses ontologies from the Open Biomedical Ontology Foundry (OBO Foundry) to represent the patient’s kinetic state at the time of measurement. The annotation system is applied to data generated by a wearable personal status monitoring (PSM) device. We demonstrate how annotated PSM data can be queried for contextualized vital signs as well as sensor algorithm configuration parameters.

Ontology is currently perceived as the solution of first resort for all problems related to biomedical terminology, and the use of description logics is seen as a minimal requirement on adequate ontology-based systems. Contrary to common conceptions, however, description logics alone are not able to prevent incorrect representations; this is because they do not come with a theory indicating what is computed by using them, just as classical arithmetic does not tell us anything about the entities that are added or subtracted. In this paper we shall show that ontology is indeed an essential part of any solution to the problems of medical terminology – but only if it is understood in the right sort of way. Ontological engineering, we shall argue, should in every case go hand in hand with a sound ontological theory.

We have begun work on two separate but related ontologies for the study of neurological diseases. The first, the Neurological Disease Ontology (ND), is intended to provide a set of controlled, logically connected classes to describe the range of neurological diseases and their associated signs and symptoms, assessments, diagnoses, and interventions that are encountered in the course of clinical practice. ND is built as an extension of the Ontology for General Medical Sciences — a high-level candidate OBO Foundry ontology that provides a set of general classes that can be used to describe general aspects of medical science. ND is being built with classes utilizing both textual and axiomatized definitions that describe and formalize the relations between instances of other classes within the ontology itself as well as to external ontologies such as the Gene Ontology, Cell Ontology, Protein Ontology, and Chemical Entities of Biological Interest. In addition, references to similar or associated terms in external ontologies, vocabularies and terminologies are included when possible. Initial work on ND is focused on the areas of Alzheimer’s and other diseases associated with dementia, multiple sclerosis, and stroke and cerebrovascular disease. Extensions to additional groups of neurological diseases are planned. The second ontology, the Neuro-Psychological Testing Ontology (NPT), is intended to provide a set of classes for the annotation of neuropsychological testing data. The intention of this ontology is to allow for the integration of results from a variety of neuropsychological tests that assay similar measures of cognitive functioning. Neuro-psychological testing is an important component in developing the clinical picture used in the diagnosis of patients with a range of neurological diseases, such as Alzheimer’s disease and multiple sclerosis, and following stroke or traumatic brain injury. NPT is being developed as an extension to the Ontology for Biomedical Investigations.

Where humans can manipulate and integrate the information they receive in subtle and ever-changing ways from context to context, computers need structured and context-free background information of a sort which ontologies can help to provide. A domain ontology captures the stable, highly general and commonly accepted core knowledge for an application domain. The domain at issue here is that of the life sciences, in particular molecular biology and bioinformatics. Contemporary life science research includes components drawn from physics, chemistry, mathematics, medicine and many other areas, and all of these dimensions, as well as fundamental philosophical issues, must be taken into account in the construction of a domain ontology. Here we describe the basic features of domain ontologies in the life sciences and show how they can be used.

The Center for Disease Control and Prevention’s Active Bacterial Core Surveillance (CDC ABCs) Program is a collaborative effort betweeen the CDC, state health departments, laboratories, and universities to track invasive bacterial pathogens of particular importance to public health [1]. The year-end surveillance reports produced by this program help to shape public policy and coordinate responses to emerging infectious diseases over time. The ABCs case report form (CRF) data represents an excellent opportunity for data reuse beyond the original surveillance purposes.

Extended entities have boundaries of two different sorts: those that do, and those that do not correspond to physical discontinuities. Call the first sort (coastlines, the surface of your nose) bona fide boundaries; and the second (the boundary of Montana, the boundary separating your upper from your lower torso) fiat boundaries. Fiat boundaries are found especially in the geographic realm, but are involved wherever language carves out portions of reality in ways which do not reflect physical discontinuities. These ideas are applied to the treatment of cognitive categorization, of the semantics of vagueness, of Quine’s indeterminacy thesis, and of standard ontological problems such as Tibbles’ tail.

In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for the domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs.

Formal principles governing best practices in classification and definition have for too long been neglected in the construction of biomedical ontologies, in ways which have important negative consequences for data integration and ontology alignment. We argue that the use of such principles in ontology construction can serve as a valuable tool in error-detection and also in supporting reliable manual curation. We argue also that such principles are a prerequisite for the successful application of advanced data integration techniques such as ontology-based multi-database querying, automated ontology alignment and ontology-based text-mining. These theses are illustrated by means of a case study of the Gene Ontology, a project of increasing importance within the field of biomedical data integration.

When a widely reused ontology appears in a new version which is not compatible with older versions, the ontologies reusing it need to be updated accordingly. Ontobull has been developed to automatically update ontologies with new term IRI(s) and associated metadata to take account of such version changes. To use the Ontobull web interface a user is required to (i) upload one or more ontology OWL source files; (ii) input an ontology term IRI mapping; and (where needed) (iii) provide update settings for ontology headers and XML namespace IDs. Using this information, the backend Ontobull Java program automatically updates the OWL ontology files with desired term IRIs and ontology metadata. The Ontobull subprogram BFOConvert supports the conversion of an ontology that imports a previous version of BFO. A use case is provided to demonstrate the features of Ontobull and BFOConvert.

Physical reality is all the reality we have, and so physical theory in the standard sense is all the ontology we need. This, at least, was an assumption taken almost universally for granted by the advocates of exact philosophy for much of the present century. Every event, it was held, is a physical event, and all structure in reality is physical structure. The grip of this assumption has perhaps been gradually weakened in recent years as far as the sciences of mind are concerned. When it comes to the sciences of external reality, however, it continues to hold sway, so that contemporary philosophers B even while devoting vast amounts of attention to the language we use in describing the world of everyday experience B still refuse to see this world as being itself a proper object of theoretical concern. Here, however, we shall argue that the usual conception of physical reality as constituting a unique bedrock of objectivity reflects a rather archaic view as to the nature of physics itself and is in fact incompatible with the development of the discipline since Newton. More specifically, we shall seek to show that the world of qualitative structures, for example of colour and sound, or the commonsense world of coloured and sounding things, can be treated scientifically (ontologically) on its own terms, and that such a treatment can help us better to understand the structures both of physical reality and of cognition.

Significant associations have been found between specific human leukocyte antigen (HLA) alleles and organ transplant rejection, autoimmune disease development, and the response to infection. Traditional searches for disease associations have conventionally measured risk associated with the presence of individual HLA alleles. However, given the high level of HLA polymorphism, the pattern of amino acid variability, and the fact that most of the HLA variation occurs at functionally important sites, it may be that a combination of variable amino acid sites shared by several alleles (shared epitopes) are better descriptors of the actual causative genetic variants. Here we describe a novel approach to genetic association analysis in which genes/proteins are broken down into smaller sequence features and then variant types defined for each feature, allowing for independent analysis of disease association with each sequence feature variant type. We have used this approach to analyze a cohort of systemic sclerosis patients and show that a sequence feature composed of specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk for systemic sclerosis.

The National Center for Biomedical Ontology is a consortium that comprises leading informaticians, biologists, clinicians, and ontologists, funded by the National Institutes of Health (NIH) Roadmap, to develop innovative technology and methods that allow scientists to record, manage, and disseminate biomedical information and knowledge in machine-processable form. The goals of the Center are (1) to help unify the divergent and isolated efforts in ontology development by promoting high quality open-source, standards-based tools to create, manage, and use ontologies, (2) to create new software tools so that scientists can use ontologies to annotate and analyze biomedical data, (3) to provide a national resource for the ongoing evaluation, integration, and evolution of biomedical ontologies and associated tools and theories in the context of driving biomedical projects (DBPs), and (4) to disseminate the tools and resources of the Center and to identify, evaluate, and communicate best practices of ontology development to the biomedical community. Through the research activities within the Center, collaborations with the DBPs, and interactions with the biomedical community, our goal is to help scientists to work more effectively in the e-science paradigm, enhancing experiment design, experiment execution, data analysis, information synthesis, hypothesis generation and testing, and understand human disease.

What follows is a contribution to the horizontal integration of warfighter intelligence data as defined in Chairman of the Joint Chiefs of Staff Instruction J2 CJCSI 3340.02AL: Horizontally integrating warfighter intelligence data improves the consumers’ production, analysis and dissemination capabilities. HI requires access (including discovery, search, retrieval, and display) to intelligence data among the warfighters and other producers and consumers via standardized services and architectures. These consumers include, but are not limited to, the combatant commands, Services, Defense agencies, and the Intelligence Community.

A consumer health information system must be able to comprehend both expert and non-expert medical vocabulary and to map between the two. We describe an ongoing project to create a new lexical database called Medical WordNet (MWN), consisting of medically relevant terms used by and intelligible to non-expert subjects and supplemented by a corpus of natural-language sentences that is designed to provide medically validated contexts for MWN terms. The corpus derives primarily from online health information sources targeted to consumers, and involves two sub-corpora, called Medical FactNet (MFN) and Medical BeliefNet (MBN), respectively. The former consists of statements accredited as true on the basis of a rigorous process of validation, the latter of statements which non-experts believe to be true. We summarize the MWN / MFN / MBN project, and describe some of its applications.

Statistics play a critical role in biological and clinical research. To promote logically consistent representation and classification of statistical entities, we have developed the Ontology of Biological and Clinical Statistics (OBCS). OBCS extends the Ontology of Biomedical Investigations (OBI), an OBO Foundry ontology supported by some 20 communities. Currently, OBCS contains 686 terms, including 381 classes imported from OBI and 147 classes specific to OBCS. The goal of this paper is to present OBCS for community critique and to describe a number of use cases designed to illustrate its potential applications. The OBCS project and source code are available at http://obcs.googlecode.com.