Background While integrating genomic sequencing into clinical care carries clear medical benefits, it also raises difficult ethical questions. Compared to traditional sequencing technologies, genomic sequencing and analysis is more likely to identify unsolicited findings (UF) and variants that cannot be classified as benign or disease-causing (variants of uncertain significance; VUS). UF and VUS pose new challenges for genetic health professionals (GHPs) who are obtaining informed consent for genomic sequencing from patients.Methods We conducted semi-structured interviews with 31 GHPs across Europe, Australia (...) and Canada to identify some of these challenges.Results Our results show that GHPs find it difficult to prepare patients to receive results because a vast amount of information is required to fully inform patients about VUS and UF. GHPs also struggle to engage patients – many of whom may be focused on ending their ‘diagnostic odyssey’ – in the informed consent process in a meaningful way. Thus, some questioned how ‘informed’ patients actually are when they agree to undergo clinical genomic sequencing.Conclusions These findings suggest a tension remains between sufficient information provision at the risk of overwhelming the patient and imparting less information at the risk of uninformed decision-making. We suggest that a shift away from ‘fully informed consent’ toward an approach aimed at realizing, as far as possible, the underlying goals that informed consent is meant to promote. (shrink)

An increasing number of European research projects return, or plan to return, individual genomic research results (IRR) to participants. While data access is a data subject’s right under the General Data Protection Regulation (GDPR), and many legal and ethical guidelines allow or require participants to receive personal data generated in research, the practice of returning results is not straightforward and raises several practical and ethical issues. Existing guidelines focusing on return of IRR are mostly project-specific, only discuss which results to (...) return, or were developed outside Europe. To address this gap, we analysed existing normative documents identified online using inductive content analysis. We used this analysis to develop a checklist of steps to assist European researchers considering whether to return IRR to participants. We then sought feedback on the checklist from an interdisciplinary panel of European experts (clinicians, clinical researchers, population-based researchers, biobank managers, ethicists, lawyers and policy makers) to refine the checklist. The checklist outlines seven major components researchers should consider when determining whether, and how, to return results to adult research participants: 1) Decide which results to return; 2) Develop a plan for return of results; 3) Obtain participant informed consent; 4) Collect and analyse data; 5) Confirm results; 6) Disclose research results; 7) Follow-up and monitor. Our checklist provides a clear outline of the steps European researchers can follow to develop ethical and sustainable result return pathways within their own research projects. Further legal analysis is required to ensure this checklist complies with relevant domestic laws. (shrink)

Although rapid genomic sequencing (RGS) is improving care for critically ill children with rare disease, it also raises important ethical questions that need to be explored as its use becomes more widespread. Two such questions relate to the degree of consent that should be required for RGS to proceed and whether it might ever be appropriate to override parents’ decisions not to allow RGS to be performed in their critically ill child. To explore these questions, we first examine the legal (...) frameworks on securing consent for genomic sequencing and how they apply to the specific context of RGS for critically ill children. We then use a tool from clinical ethics, the Zone of Parental Discretion, to explore two case studies and identify under which circumstances it might be appropriate for parental refusal of RGS to be overridden. We argue that RGS may be a context where, in addition to assessing the complexity of the test offered, it is ethically appropriate to consider an effect on patient outcomes when deciding the degree of consent required. We also suggest that there are some contexts where it may be ethically justified to perform RGS, even when it is actively against the wishes of the parents. More work is needed to examine exactly how ‘time-sensitive’ exceptions to current guidance on consent for genomic sequencing could be formulated and operationalised for RGS for critically ill-children. (shrink)

Ontologies are being used increasingly to promote the reusability of scientific information by allowing heterogeneous data to be integrated under a common, normalized representation. Definitions play a central role in the use of ontologies both by humans and by computers. Textual definitions allow ontologists and data curators to understand the intended meaning of ontology terms and to use these terms in a consistent fashion across contexts. Logical definitions allow machines to check the integrity of ontologies and reason over data annotated (...) with ontology terms to make inferences that promote knowledge discovery. Therefore, it is important not only to include in ontologies multiple types of definitions in both formal and in natural languages, but also to ensure that these definitions meet good quality standards so they are useful. While tools such as Protégé can assist in creating well-formed logical definitions, producing good definitions in a natural language is still to a large extent a matter of human ingenuity supported at best by just a small number of general principles. For lack of more precise guidelines, definition authors are often left to their own personal devices. This paper aims to fill this gap by providing the ontology community with a set of principles and conventions to assist in definition writing, editing, and validation, by drawing on existing definition writing principles and guidelines in lexicography, terminology, and logic. (shrink)

Medical imaging is predominantly a visual field. In this context, prenatal ultrasound images assume intense social, ethical, and psychological significance by virtue of the subject they represent: the fetus. This feature, along with the sophistication introduced by three-dimensional ultrasound imaging that allows improved visualization of the fetus, has contributed to the common impression that prenatal ultrasound scans are like photographs of the fetus. In this article we discuss the consistency of such a comparison. First, we investigate the epistemic role of (...) both analogic and digital photographic images as visual information-providing representations holding a high degree of objectivity. Second, we examine the structure and process of production of ultrasound scans and argue that a comparison between two-dimensional ultrasound and photography is justified. This is in contrast to 3D ultrasound images that, due to the intensive mathematical processing involved in their production, present some structural issues that obfuscate their ontological and epistemic status. (shrink)

To understand what ontologies do through their definitions, we propose a theoretical explanation of the functions of definitions in ontologies backed by empirical neuropsychological studies. Our goal is to show how these functions should motivate (i) the systematic inclusion of definitions in ontologies and (ii) the adaptation of definition content and form to the specific context of use of ontologies.

Predictive genetic testing for susceptibility to psychiatric conditions is likely to become part of standard practice. Because the onset of most psychiatric diseases is in late adolescence or early adulthood, testing minors could lead to early identification that may prevent or delay the development of these disorders. However, due to their complex aetiology, psychiatric genetic testing does not provide the immediate medical benefits that current guidelines require for testing minors. While several authors have argued non-medical benefits may play a crucial (...) role in favour of predictive testing for other conditions, little research has explored such a role in psychiatric disorders. This paper outlines the potential non-medical benefits and harms of psychiatric genetic testing in minors in order to consider whether the non-medical benefits could ever make such testing appropriate. Five non-medical themes arise in the literature: psychological impacts, autonomy/self-determination, implications of the biomedical approach, use of financial and intellectual resources, and discrimination. Non-medical benefits were prominent in all of them, suggesting that psychiatric genetic testing in minors may be appropriate in some circumstances. Further research needs to empirically assess these potential non-medical benefits, incorporate minors in the debate, and include normative reflection to evaluate the very purposes and motivations of psychiatric genetic testing in minors. (shrink)

Objective: To examine i) how ethical frameworks can be used in concrete cases of parent–doctors’ disagreements for extremely preterm infants born in the grey zone to guide such difficult decision-making; and ii) what challenges stakeholders may encounter in using these frameworks. Design: We did a case analysis of a concrete case of parent–doctor disagreement in the grey zone using two ethical frameworks: the best interest standard and the zone of parental discretion. Results: Both ethical frameworks entailed similar advantages and challenges. (...) They have the potential 1) to facilitate decision-making because they follow a structured method; 2) to clarify the situation because all relevant ethical issues are explored; and 3) to facilitate reaching an agreement because all parties can explain their views. We identified three main challenges. First, how to objectively evaluate the risk of severe disability. Second, parents’ interests should be considered but it is not clear to what extent. Third, this is a value-laden situation and different people have different values, meaning that the frameworks are at least partially subjective. Conclusions: These challenges do not mean that the ethical frameworks are faulty; rather, they reflect the complexity and the sensitivity of cases in the grey zone. (shrink)

The article [Title], written by [AuthorNames], was originally published electronically on the publisher’s internet portal on [date of OnlineFirst publication] without open access.

When developing the Ontology of Biomedical Investigations (OBI), the process of adding classes with similar patterns of logical definition is time consuming, error prone, and requires an editor to...

Definitions vary according to context of use and target audience. They must be made relevant for each context to fulfill their cognitive and linguistic goals. This involves adapting their logical structure, type of content, and form to each context of use. We examine from these perspectives the case of definitions in ontologies.

This paper proposes a reformulation of the treatment of boundaries, at parts and aggregates of entities in Basic Formal Ontology. These are currently treated as mutually exclusive, which is inadequate for biological representation since some entities may simultaneously be at parts, boundaries and/or aggregates. We introduce functions which map entities to their boundaries, at parts or aggregations. We make use of time, space and spacetime projection functions which, along the way, allow us to develop a simple temporal theory.

Basic Formal Ontology (BFO) is a top-level ontology consisting of thirty-six classes, designed to support information integration, retrieval, and analysis across all domains of scientific investigation, presently employed in over 350 ontology projects around the world. BFO is a genuine top-level ontology, containing no terms particular to material domains, such as physics, medicine, or psychology. In this paper, we demonstrate how a series of cases illustrating common types of change may be represented by universals, defined classes, and relations employing the (...) BFO framework. We provide discussion of these cases to provide a template for other ontologists using BFO, as well as to facilitate comparison with the strategies proposed by ontologists using different top-level ontologies. (shrink)

The value of any kind of data is greatly enhanced when it exists in a form that allows it to be integrated with other data. One approach to integration is through the annotation of multiple bodies of data using common controlled vocabularies or ‘ontologies’. Unfortunately, the very success of this approach has led to a proliferation of ontologies which itself creates obstacles to integration. The Open Biomedical Ontologies (OBO) consortium has set in train a strategy to overcome this problem. Existing (...) OBO ontologies, including the Gene Ontology, are undergoing a process of coordinated reform and new ontologies being created on the basis of an evolving set of shared principles governing ontology development. The result is an expanding family of ontologies designed to be interoperable, logically well-formed, and to incorporate accurate representations of biological reality. We describe the OBO Foundry initiative, and provide guidelines for those who might wish to become involved. (shrink)

This volume of essays is an important introduction to the thought of one of the twentieth century's most significant yet underappreciated philosophers, Richard McKeon. The originator of philosophical pluralism, McKeon made extraordinary contributions to philosophy, to international relations, and to theory-formation in the communication arts, aesthetics, the organization of knowledge, and the practical sciences. This collection, which includes a philosophical autobiography as well as the out-of-print title essay "Freedom and History" and a previously unpublished essay on "Philosophic Semantics and Philosophic (...) Inquiry," is a testimony to the range and systematic power of McKeon's thinking for the social sciences and the humanities. (shrink)

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to (...) existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource providing details on the people, policies, and issues being addressed in association with OBI. (shrink)

Biological ontologies are used to organize, curate, and interpret the vast quantities of data arising from biological experiments. While this works well when using a single ontology, integrating multiple ontologies can be problematic, as they are developed independently, which can lead to incompatibilities. The Open Biological and Biomedical Ontologies Foundry was created to address this by facilitating the development, harmonization, application, and sharing of ontologies, guided by a set of overarching principles. One challenge in reaching these goals was that the (...) OBO principles were not originally encoded in a precise fashion, and interpretation was subjective. Here we show how we have addressed this by formally encoding the OBO principles as operational rules and implementing a suite of automated validation checks and a dashboard for objectively evaluating each ontology’s compliance with each principle. This entailed a substantial effort to curate metadata across all ontologies and to coordinate with individual stakeholders. We have applied these checks across the full OBO suite of ontologies, revealing areas where individual ontologies require changes to conform to our principles. Our work demonstrates how a sizable federated community can be organized and evaluated on objective criteria that help improve overall quality and interoperability, which is vital for the sustenance of the OBO project and towards the overall goals of making data FAIR. Competing Interest StatementThe authors have declared no competing interest. (shrink)

Intensified and extensive data production and data storage are characteristics of contemporary western societies. Health data sharing is increasing with the growth of Information and Communication Technology platforms devoted to the collection of personal health and genomic data. However, the sensitive and personal nature of health data poses ethical challenges when data is disclosed and shared even if for scientific research purposes. With this in mind, the Science and Values Working Group of the COST Action CHIP ME ‘Citizen's Health through (...) public-private Initiatives: Public health, Market and Ethical perspectives’ identified six core values they considered to be essential for the ethical sharing of health data using ICT platforms. We believe that using this ethical framework will promote respectful scientific practices in order to maintain individuals’ trust in research. We use these values to analyse five ICT platforms and explore how emerging data sharing platforms are reconfiguring the data sharing experience from a range of perspectives. We discuss which types of values, rights and responsibilities they entail and enshrine within their philosophy or outlook on what it means to share personal health information. Through this discussion we address issues of the design and the development process of personal health data and patient-oriented infrastructures, as well as new forms of technologically-mediated empowerment. (shrink)

Recently, Australia became the second jurisdiction worldwide to legalize the use of mitochondrial donation technology. The Mitochondrial Donation Law Reform (Maeve’s Law) Bill 2021 allows individuals with a family history of mitochondrial disease to access assisted reproductive techniques that prevent the inheritance of mitochondrial disease. Using inductive content analysis, we assessed submissions sent to the Senate Committee as part of a programme of scientific inquiry and public consultation that informed drafting of the Bill. These submissions discussed a range of bioethical (...) and legal considerations of central importance to the political debate. Significantly, submissions from those with a first-hand experience of mitochondrial disease, including clinicians and those with a family history of mitochondrial disease, were in strong support of this legislation. Those in support of the Bill commended the two-staged approach and rigorous licencing requirements as part of the Bill’s implementation strategy. Submissions which outlined arguments against the legislation either opposed the use of these techniques in general or opposed aspects of the implementation strategy in Australia. These findings offer a window into the ethical arguments and perspectives that matter most to those Australians who took part in the Senate inquiry into mitochondrial donation. The insights garnered from these submissions may be used to help refine policy and guidelines as the field progresses. (shrink)

Genomic sequencing technologies (GS) pose novel challenges not seen in older genetic technologies, making traditional standards for fully informed consent difficult or impossible to meet. This is due to factors including the complexity of the test and the broad range of results it may identify. Meaningful informed consent is even more challenging to secure in contexts involving significant time constraints and emotional distress, such as when rapid genomic testing (RGS) is performed in neonatal intensive care units. In this article, we (...) propose that informed consent matters not for its own sake, but because obtaining it furthers a range of morally important goals, such as promoting autonomy, well‐being, and trust in medicine. These goals form the basis of a new framework [PROmoting Morally Important Consent Ends (PROMICE)] for assessing the ethical appropriateness of various informed consent models. We illustrate this framework with two examples: (a) a tiered and layered consent model for obtaining consent for GS, and (b) consent for RGS in critically ill newborns. We conclude that appropriately—rather than fully—informed consent provides the correct standard for genomic medicine and research. (shrink)

Participation in healthcare decision-making is considered to be an important right of minors, and is highlighted in both international legislation and public policies. However, despite the legal recognition of children’s rights to participation, and also the benefits that children experience by their involvement, there is evidence that legislation is not always translated into healthcare practice. There are a number of factors that may impact on the ability of the child to be involved in decisions regarding their medical care. Some of (...) these factors relate to the child, including their capacity to be actively involved in these decisions. Others relate to the family situation, sociocultural context, or the underlying beliefs and practices of the healthcare provider involved. In spite of these challenges to including children in decisions regarding their clinical care, we argue that it is an important factor in their treatment. The extent to which children should participate in this process should be determined on a case-by-case basis, taking all of the potential barriers into account. (shrink)

Representing species-specific proteins and protein complexes in ontologies that are both human and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because (...) proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. (shrink)

Genomic research can reveal ‘unsolicited’ or ‘incidental’ findings that are of potential health or reproductive significance to participants. It is widely thought that researchers have a moral obligation, grounded in the duty of easy rescue, to return certain kinds of unsolicited findings to research participants. It is less widely thought that researchers have a moral obligation to actively look for health-related findings. This paper examines whether there is a moral obligation, grounded in the duty of easy rescue, to actively hunt (...) for genomic secondary findings. We begin by showing how the duty to disclose individual research findings can be grounded in the duty of easy rescue. Next, we describe a parallel moral duty, also grounded in the duty of easy rescue, to actively hunt for such information. We then consider six possible objections to our argument, each of which we find unsuccessful. Some of these objections provide reason to limit the scope of the duty to look for secondary findings, but none provide reason to reject this duty outright. We argue that under a certain range of circumstances, researchers are morally required to hunt for these kinds of secondary findings. Although these circumstances may not currently obtain, genomic researchers will likely acquire an obligation to hunt for secondary findings as the field of genomics continues to evolve. (shrink)

Although the last decade has seen a proliferation of ontological approaches to arguments, many of them employ ad hoc solutions to representing arguments, lack interoperability with other ontologies, or cover arguments only as part of a broader approach to evidence. To provide a better ontological representation of arguments, we present the Arguments Ontology (ArgO), a small ontology for arguments that is designed to be imported and easily extended by researchers who work in different upper-level ontology frameworks, different logics, and different (...) approaches to argument evaluation. Unlike most ontological approaches to arguments, ArgO utilizes Basic Formal Ontology (BFO) as an upper-level ontology, and may be used alongside other commonly used ontologies in the BFO framework, including boththe Information Artifact Ontology (IAO), and the Information Entity Ontology (INFO). Critically, our proposal is principled, based on rigorous definitions and formal axioms out of which characterizations of arguments naturally fall. It is our hope that ArgO may assist researchers in many projects, including: integrating heterogeneous sources of evidence, structuring the content of semantic wikis, and enhancing semantic reasoning. (shrink)

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. (shrink)

While the Web Ontology Language (OWL) provides a mechanism to import ontologies, this mechanism is not always suitable. Current editing tools present challenges for working with large ontologies an...

We are developing the Neurological Disease Ontology (ND) to provide a framework to enable representation of aspects of neurological diseases that are relevant to their treatment and study. ND is a representational tool that addresses the need for unambiguous annotation, storage, and retrieval of data associated with the treatment and study of neurological diseases. ND is being developed in compliance with the Open Biomedical Ontology Foundry principles and builds upon the paradigm established by the Ontology for General Medical Science (OGMS) (...) for the representation of entities in the domain of disease and medical practice. Initial applications of ND will include the annotation and analysis of large data sets and patient records for Alzheimer’s disease, multiple sclerosis, and stroke. (shrink)

Interoperability across data sets is a key challenge for quantitative histopathological imaging. There is a need for an ontology that can support effective merging of pathological image data with associated clinical and demographic data. To foster organized, cross-disciplinary, information-driven collaborations in the pathological imaging field, we propose to develop an ontology to represent imaging data and methods used in pathological imaging and analysis, and call it Quantitative Histopathological Imaging Ontology – QHIO. We apply QHIO to breast cancer hot-spot detection with (...) the goal of enhancing reliability of detection by promoting the sharing of data between image analysts. (shrink)

How do we find what is clinically significant in the swarms of data being generated by today’s diagnostic technologies? As electronic records become ever more prevalent – and digital imaging and genomic, proteomic, salivaomics, metabalomics, pharmacogenomics, phenomics and transcriptomics techniques become commonplace – fdifferent clinical and biological disciplines are facing up to the need to put their data houses in order to avoid the consequences of an uncontrolled explosion of different ways of describing information. We describe a new strategy to (...) advance the consistency of data in the dental research community. The strategy is based on the idea that existing systems for data collection in dental research will continue to be used, but proposes a methodology in which past, present and future data will be described using a consensus-based controlled structured vocabulary called the Ontology for Dental Research (ODR). (shrink)

Genomic sequencing (GS) is increasingly used in paediatric medicine to aid in screening, research and treatment. Some health systems are trialling GS as a first-line test in newborn screening programmes. Questions about what to do with genomic data after it has been generated are becoming more pertinent. While other research has outlined the ethical reasons for storing deidentified genomic data to be used in research, the ethical case for storing data for future clinical use has not been explicated. In this (...) paper, we examine the ethical case for storing genomic data with the intention of using it as a lifetime health resource. In this model, genomic data would be stored with the intention of reanalysis at certain points through one’s life. We argue this could benefit individuals and create an important public resource. However, several ethical challenges must first be met to achieve these benefits. We explore issues related to privacy, consent, justice and equality. We conclude by arguing that health systems should be moving towards futures that allow for the sequential interrogation of genomic data throughout the lifespan. (shrink)

Background There is ongoing debate regarding whether and under which circumstances secondary findings (SF) should be offered in the pediatric context. Although studies have examined patient perspectives on receiving SF, little research has been conducted examining the experiences of clinicians offering SF to parents of newborns receiving genomic sequencing for a recently diagnosed medical condition.Methods To address this, we conducted qualitative interviews exploring the views and experiences of 12 clinicians who offered SF to parents of infants who had diagnostic exome (...) sequencing (ES) to identify the cause of their hearing loss. Interviews explored clinicians’ accounts of parents’ choices and decision-making about receiving SF, their views on whether and when to offer SF, their experiences returning SF, and any ethical challenges they encountered. Interviews were audio-recorded, transcribed and analyzed using inductive content analysis.Results Clinicians reported parents who declined all SF often felt finding out about future conditions unrelated to their child’s hearing loss may be unhelpful, or even harmful, or were overwhelmed by their child’s diagnosis. Clinicians also reported that some parents chose SF because they felt obliged to, even if they did not want to receive them. They explained that while some parents experienced decision-making regarding SF as positive, for others, this process was challenging or distressing. While clinicians generally agreed SF should be offered, mainly to promote parental choice, most felt SF should be offered after disclosing diagnostic results, primarily to avoid overwhelming parents. Clinicians encountered several ethical challenges, including balancing parental autonomy with non-maleficence, wanting to report or not report certain SF, and questioning whether parents can make an autonomous choice regarding SF.Conclusions Our findings, which are novel as they relate to parents of young infants with a recent diagnosis of hearing loss, add new insights into clinicians’ and parents’ decision-making regarding SF in pediatrics. (shrink)

The Protein Ontology provides terms for and supports annotation of species-specific protein complexes in an ontology framework that relates them both to their components and to species-independent families of complexes. Comprehensive curation of experimentally known forms and annotations thereof is expected to expose discrepancies, differences, and gaps in our knowledge. We have annotated the early events of innate immune signaling mediated by Toll-Like Receptor 3 and 4 complexes in human, mouse, and chicken. The resulting ontology and annotation data set has (...) allowed us to identify species-specific gaps in experimental data and possible functional differences between species, and to employ inferred structural and functional relationships to suggest plausible resolutions of these discrepancies and gaps. (shrink)

Although Next Generation Sequencing (NGS) has increased our ability to test and diagnose, its results are often not clear-cut and require a complex interpretation and negotiation process by both healthcare professionals and patients involved. In this paper, we explore how diagnoses identified through NGS are socially shaped under influence of the broader social context. Using an analytical framework stemming from the sociology of health and illness and science and technology studies, with a focus on the construction of diagnosis and the (...) role of uncertainty in medicine, we analyze the existing corpus of literature on NGS diagnostic practices. We show how in this early implementation phase of NGS, in which standardization efforts are not yet solidified, the boundary struggles around diagnoses obtained through NGS are particularly visible. We discuss the different steps in the diagnosis shaping process and what it subsequently entails to give and a receive a diagnosis using NGS. (shrink)

Letter commenting on the paper Barry Smith, Louis J. Goldberg, Alan Ruttenberg & Michael Glick, "Ontology and the Future of Dental Research Informatics", Journal of the American Dental Association 141 2010;(10):1173-75 with responses by the authors of the paper.

BackgroundCarrier screening is generally performed with the aim of identifying healthy couples at risk of having a child affected with a monogenic disorder to provide them with reproductive options. Expanded carrier screening, which provides the opportunity for multiple conditions to be screened in one test, offers a more cost-effective and comprehensive option than screening for single disorders. However, implementation of ECS at a population level would have implications for genetic counseling practice.MethodsWe conducted semi-structured interviews with sixteen European clinical and molecular (...) geneticists with expertise in carrier screening to explore their views on the implementation of ECS in the clinical setting.ResultsUsing inductive content analysis, we identified content categories relevant to the pre- and post-test settings. Participants believed ECS would ideally be targeted at couples before pregnancy. There was some disagreement regarding the acceptability of performing ECS in individuals, with several participants actively opposing individual-based screening. In addition, participants discussed the importance of ensuring informed and voluntary participation in ECS, recommending measures to minimize external pressure on prospective parents to undergo testing. A need for adequate counseling to foster informed, autonomous reproductive decision-making and provide support for couples found to be at risk was emphasized.ConclusionsPractical challenges in optimizing pre-test education and post-test counseling should not be underestimated and they should be carefully addressed before implementing ECS in the clinical setting. (shrink)

Monoclonal antibodies are essential biomedical research and clinical reagents that are produced by companies and research laboratories. The NIAID ImmPort (Immunology Database and Analysis Portal) resource provides a long-term, sustainable data warehouse for immunological data generated by NIAID, DAIT and DMID funded investigators for data archiving and re-use. A variety of immunological data is generated using techniques that rely upon monoclonal antibody reagents, including flow cytometry, immunofluorescence, and ELISA. In order to facilitate querying, integration, and reuse of data, standardized terminology (...) for describing monoclonal antibody reagents and their targets needs to be used for annotating data submitted to ImmPort. (shrink)

Identification of non-coding RNAs (ncRNAs) has been significantly improved over the past decade. On the other hand, semantic annotation of ncRNA data is facing critical challenges due to the lack of a comprehensive ontology to serve as common data elements and data exchange standards in the field. We developed the Non-Coding RNA Ontology (NCRO) to handle this situation. By providing a formally defined ncRNA controlled vocabulary, the NCRO aims to fill a specific and highly needed niche in semantic annotation of (...) large amounts of ncRNA biological and clinical data. (shrink)

Vaccine research, as well as the development, testing, clinical trials, and commercial uses of vaccines involve complex processes with various biological data that include gene and protein expression, analysis of molecular and cellular interactions, study of tissue and whole body responses, and extensive epidemiological modeling. Although many data resources are available to meet different aspects of vaccine needs, it remains a challenge how we are to standardize vaccine annotation, integrate data about varied vaccine types and resources, and support advanced vaccine (...) data analysis and inference. To address these problems, the community-based Vaccine Ontology (VO) has been developed through collaboration with vaccine researchers and many national and international centers and programs, including the National Center for Biomedical Ontology (NCBO), the Infectious Disease Ontology (IDO) Initiative, and the Ontology for Biomedical Investigations (OBI). VO utilizes the Basic Formal Ontology (BFO) as the top ontology and the Relation Ontology (RO) for definition of term relationships. VO is represented in the Web Ontology Language (OWL) and edited using the Protégé-OWL. Currently VO contains more than 2000 terms and relationships. VO emphasizes on classification of vaccines and vaccine components, vaccine quality and phenotypes, and host immune response to vaccines. These reflect different aspects of vaccine composition and biology and can thus be used to model individual vaccines. More than 200 licensed vaccines and many vaccine candidates in research or clinical trials have been modeled in VO. VO is being used for vaccine literature mining through collaboration with the National Center for Integrative Biomedical Informatics (NCIBI). Multiple VO applications will be presented. (shrink)

The translational research community, in general, and the Clinical and Translational Science Awards (CTSA) community, in particular, share the vision of repurposing EHRs for research that will improve the quality of clinical practice. Many members of these communities are also aware that electronic health records (EHRs) suffer limitations of data becoming poorly structured, biased, and unusable out of original context. This creates obstacles to the continuity of care, utility, quality improvement, and translational research. Analogous limitations to sharing objective data in (...) other areas of the natural sciences have been successfully overcome by developing and using common ontologies. This White Paper presents the authors’ rationale for the use of ontologies with computable semantics for the improvement of clinical data quality and EHR usability formulated for researchers with a stake in clinical and translational science and who are advocates for the use of information technology in medicine but at the same time are concerned by current major shortfalls. This White Paper outlines pitfalls, opportunities, and solutions and recommends increased investment in research and development of ontologies with computable semantics for a new generation of EHRs. (shrink)

Identification of non-coding RNAs (ncRNAs) has been significantly enhanced due to the rapid advancement in sequencing technologies. On the other hand, semantic annotation of ncRNA data lag behind their identification, and there is a great need to effectively integrate discovery from relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a precisely defined ncRNA controlled vocabulary, which can fill a specific and highly needed niche in unification of ncRNA biology.