Toward a view-oriented approach for aligning RDF-based biomedical repositories.

INTRODUCTION: This article is part of the Focus Theme of METHODS of Information in Medicine on "Managing Interoperability and Complexity in Health Systems". BACKGROUND: The need for complementary access to multiple RDF databases has fostered new lines of research, but also entailed new challenges due to data representation disparities. While several approaches for RDF-based database integration have been proposed, those focused on schema alignment have become the most widely adopted. All state-of-the-art solutions for aligning RDF-based sources resort to a simple technique inherited from legacy relational database integration methods. This technique - known as element-to-element (e2e) mappings - is based on establishing 1:1 mappings between single primitive elements - e.g. concepts, attributes, relationships, etc. - belonging to the source and target schemas. However, due to the intrinsic nature of RDF - a representation language based on defining tuples < subject, predicate, object > -, one may find RDF elements whose semantics vary dramatically when combined into a view involving other RDF elements - i.e. they depend on their context. The latter cannot be adequately represented in the target schema by resorting to the traditional e2e approach. These approaches fail to properly address this issue without explicitly modifying the target ontology, thus lacking the required expressiveness for properly reflecting the intended semantics in the alignment information. OBJECTIVES: To enhance existing RDF schema alignment techniques by providing a mechanism to properly represent elements with context-dependent semantics, thus enabling users to perform more expressive alignments, including scenarios that cannot be adequately addressed by the existing approaches. METHODS: Instead of establishing 1:1 correspondences between single primitive elements of the schemas, we propose adopting a view-based approach. The latter is targeted at establishing mapping relationships between RDF subgraphs - that can be regarded as the equivalent of views in traditional databases -, rather than between single schema elements. This approach enables users to represent scenarios defined by context-dependent RDF elements that cannot be properly represented when adopting the currently existing approaches. RESULTS: We developed a software tool implementing our view-based strategy. Our tool is currently being used in the context of the European Commission funded p-medicine project, targeted at creating a technological framework to integrate clinical and genomic data to facilitate the development of personalized drugs and therapies for cancer, based on the genetic profile of the patient. We used our tool to integrate different RDF-based databases - including different repositories of clinical trials and DICOM images - using the Health Data Ontology Trunk (HDOT) ontology as the target schema. CONCLUSIONS: The importance of database integration methods and tools in the context of biomedical research has been widely recognized. Modern research in this area - e.g. identification of disease biomarkers, or design of personalized therapies - heavily relies on the availability of a technical framework to enable researchers to uniformly access disparate repositories. We present a method and a tool that implement a novel alignment method specifically designed to support and enhance the integration of RDF-based data sources at schema (metadata) level. This approach provides an increased level of expressiveness compared to other existing solutions, and allows solving heterogeneity scenarios that cannot be properly represented using other state-of-the-art techniques.

Discussion of "Biomedical informatics: we are what we publish".

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Biomedical Informatics: We Are What We Publish", written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the Elkin et al. paper. In subsequent issues the discussion can continue through letters to the editor.

Nanoinformatics knowledge infrastructures: bringing efficient information management to nanomedical research.

Nanotechnology represents an area of particular promise and significant opportunity across multiple scientific disciplines. Ongoing nanotechnology research ranges from the characterization of nanoparticles and nanomaterials to the analysis and processing of experimental data seeking correlations between nanoparticles and their functionalities and side effects. Due to their special properties, nanoparticles are suitable for cellular-level diagnostics and therapy, offering numerous applications in medicine, e.g. development of biomedical devices, tissue repair, drug delivery systems and biosensors. In nanomedicine, recent studies are producing large amounts of structural and property data, highlighting the role for computational approaches in information management. While in vitro and in vivo assays are expensive, the cost of computing is falling. Furthermore, improvements in the accuracy of computational methods (e.g. data mining, knowledge discovery, modeling and simulation) have enabled effective tools to automate the extraction, management and storage of these vast data volumes. Since this information is widely distributed, one major issue is how to locate and access data where it resides (which also poses data-sharing limitations). The novel discipline of nanoinformatics addresses the information challenges related to nanotechnology research. In this paper, we summarize the needs and challenges in the field and present an overview of extant initiatives and efforts.

Nanoinformatics: developing new computing applications for nanomedicine.

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended "nanotype" to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others.

Biomedical informatics publications: a global perspective. Part II: Journals.

BACKGROUND: Biomedical Informatics (BMI) is a broad discipline, having evolved from both Medical Informatics (MI) and Bioinformatics (BI). An analysis of publications in the fieldshould provide an indication about the geographic distribution of BMI research contributions and possible lessons for the future, both for research and professional practice. OBJECTIVES: In part I of our analysis of biomedical informatics publications we presented results from BMI conferences. In this second part, we analyse BMI journals, which provide a broader perspective and comparison between data from conferences and journals that ought to confirm or suggest alternatives to the original distributional findings from the conferences. METHODS: We manually collected data about authors and their geographical origin from various MI journals: the International Journal of Medical Informatics (IJMI), the Journal of Biomedical Informatics (JBI), Methods of In formation in Medicine (MIM) and The Journal of the American Medical Informatics Association (JAMIA). Focusing on first authors, we also compared these findings with data from the journal Bioinformatics. RESULTS: Our results confirm those obtained in our analysis of BMI conferences - that local and regional authors favor their corresponding MI journals just as they do their conferences. Consideration of other factors, such as the increasingly open source nature of data and software tools, is consistent with these findings. CONCLUSIONS: Our analysis suggests various indicators that could lead to further, deeper analyses, and could provide additional insights for future BMI research and professional activities.

Biomedical informatics publications: a global perspective: part I: conferences.

BACKGROUND: In the past decade, Medical Informatics (MI) and Bioinformatics (BI) have converged towards a new discipline, called Biomedical Informatics (BMI) bridging informatics methods across the spectrum from genomic research to personalized medicine and global healthcare. This convergence still raises challenging research questions which are being addressed by researchers internationally, which in turn raises the question of how biomedical informatics publications reflect the contributions from around the world in documenting the research. OBJECTIVES: To analyse the worldwide participation of biomedical informatics researchers from professional groups and societies in the best-known scientific conferences in the field. The analysis is focused on their geographical affiliation, but also includes other features, such as the impact and recognition of the conferences. METHODS: We manually collected data about authors of papers presented at three major MI conferences: Medinfo, MIE and the AMIA symposium. In addition, we collected data from a BI conference, ISMB, as a comparison. Finally, we analyzed the impact and recognition of these conferences within their scientific contexts. RESULTS: Data indicate a predominance of local authors at the regional conferences (AMIA and MIE), whereas other conferences with a world-wide scope (Medinfo and ISMB) had broader participation. Our analysis shows that the influence of these conferences beyond the discipline remains somewhat limited. CONCLUSIONS: Our results suggest that for BMI to be recognized as a broad discipline, both in the geographical and scientific sense, it will need to extend the scope of collaborations and their interdisciplinary impacts worldwide.

Biomedical informatics--a confluence of disciplines?

BACKGROUND: Biomedical informatics is a broad discipline that borrows many methods and techniques from other disciplines. OBJECTIVE: To reflect a) on the character of biomedical informatics and to determine whether it is multi-disciplinary or inter-disciplinary; b) on the question whether biomedical informatics is more than the sum of its supporting disciplines and c) on the position of biomedical informatics with respect to related disciplines. METHOD: Inviting an international group of experts in biomedical informatics and related disciplines on the occasion of the 50th anniversary of Methods of Information in Medicine to present their viewpoints. RESULTS AND CONCLUSIONS: This paper contains the reflections of a number of the invited experts on the character of biomedical informatics. Most of the authors agree that biomedical informatics is an interdisciplinary field of study where researchers with different scientific backgrounds alone or in combination carry out research. Biomedical informatics is a very broad scientific field and still expanding, yet comprised of a constructive aspect (designing and building systems). One author expressed that the essence of biomedical informatics, as opposed to related disciplines, lies in the modelling of the biomedical content. Interdisciplinarity also has consequences for education. Maintaining rigid disciplinary structures does not allow for sufficient adaptability to capitalize on important trends nor to leverage the influences these trends may have on biomedical informatics. It is therefore important for students to become aware of research findings in related disciplines. In this respect, it was also noted that the fact that many scientific fields use different languages and that the research findings are stored in separate bibliographic databases makes it possible that potentially connected findings will never be linked, despite the fact that these findings were published. Bridges between the sciences are needed for the success of biomedical informatics.

Biomedical ontologies: toward scientific debate.

OBJECTIVES: Biomedical ontologies have been very successful in structuring knowledge for many different applications, receiving widespread praise for their utility and potential. Yet, the role of computational ontologies in scientific research, as opposed to knowledge management applications, has not been extensively discussed. We aim to stimulate further discussion on the advantages and challenges presented by biomedical ontologies from a scientific perspective. METHODS: We review various aspects of biomedical ontologies going beyond their practical successes, and focus on some key scientific questions in two ways. First, we analyze and discuss current approaches to improve biomedical ontologies that are based largely on classical, Aristotelian ontological models of reality. Second, we raise various open questions about biomedical ontologies that require further research, analyzing in more detail those related to visual reasoning and spatial ontologies. RESULTS: We outline significant scientific issues that biomedical ontologies should consider, beyond current efforts of building practical consensus between them. For spatial ontologies, we suggest an approach for building "morphospatial" taxonomies, as an example that could stimulate research on fundamental open issues for biomedical ontologies. CONCLUSIONS: Analysis of a large number of problems with biomedical ontologies suggests that the field is very much open to alternative interpretations of current work, and in need of scientific debate and discussion that can lead to new ideas and research directions.

International efforts in nanoinformatics research applied to nanomedicine.

BACKGROUND: Nanomedicine and nanoinformatics are novel disciplines facing substantial challenges. Since nanomedicine involves complex and massive data analysis and management, a new discipline named nanoinformatics is now emerging to provide the vision and the informatics methods and tools needed for such purposes. Methods from biomedi-cal informatics may prove applicable with some adaptation despite nanomedicine involving different biophysical and biochemical characteristics of nanomaterials and corresponding differences in information complexity. OBJECTIVES: We analyze recent initiatives and opportunities for research in nanomedicine and nanoinformatics as well as the previous experience of the authors, particularly in the context of a European project named ACTION-Grid. In this project the authors aimed to create a collaborative environment in biomedical and nanomedical research among countries in Europe, Western Balkans, Latin America, North Africa and the USA. METHODS: We review and analyze the rationale and scientific issues behind the new fields of nanomedicine and nanoinformatics. Such a review is linked to actual research projects and achievements of the authors within their groups. RESULTS: The work of the authors at the intersection between these two areas is presented. We also analyze several research initiatives that have recently emerged in the EU and USA context and highlight some ideas for future action at the international level. CONCLUSIONS: Nanoinformatics aims to build new bridges between medicine, nanotechnology and informatics, allowing the application of computational methods in the nano-related areas. Opportunities for world-wide collaboration are already emerging and will be influential in advancing the field.

Integration of relational and textual biomedical sources. A pilot experiment using a semi-automated method for logical schema acquisition.

OBJECTIVES: Bringing together structured and text-based sources is an exciting challenge for biomedical informaticians, since most relevant biomedical sources belong to one of these categories. In this paper we evaluate the feasibility of integrating relational and text-based biomedical sources using: i) an original logical schema acquisition method for textual databases developed by the authors, and ii) OntoFusion, a system originally designed by the authors for the integration of relational sources. METHODS: We conducted an integration experiment involving a test set of seven differently structured sources covering the domain of genetic diseases. We used our logical schema acquisition method to generate schemas for all textual sources. The sources were integrated using the methods and tools provided by OntoFusion. The integration was validated using a test set of 500 queries. RESULTS: A panel of experts answered a questionnaire to evaluate i) the quality of the extracted schemas, ii) the query processing performance of the integrated set of sources, and iii) the relevance of the retrieved results. The results of the survey show that our method extracts coherent and representative logical schemas. Experts' feedback on the performance of the integrated system and the relevance of the retrieved results was also positive. Regarding the validation of the integration, the system successfully provided correct results for all queries in the test set. CONCLUSIONS: The results of the experiment suggest that text-based sources including a logical schema can be regarded as equivalent to structured databases. Using our method, previous research and existing tools designed for the integration of structured databases can be reused - possibly subject to minor modifications - to integrate differently structured sources.

Biomedical informatics and the convergence of Nano-Bio-Info-Cogno (NBIC) technologies.

OBJECTIVES: To analyze the role that biomedical informatics could play in the application of the NBIC Converging Technologies in the medical field and raise awareness of these new areas throughout the Biomedical Informatics community. METHODS: Review of the literature and analysis of the reference documents in this domain from the biomedical informatics perspective. Detailing existing developments showing that partial convergence of technologies have already yielded relevant results in biomedicine (such as bioinformatics or biochips). Input from current projects in which the authors are involved is also used. RESULTS: Information processing is a key issue in enabling the convergence of NBIC technologies. Researchers in biomedical informatics are in a privileged position to participate and actively develop this new scientific direction. The experience of biomedical informaticians in five decades of research in the medical area and their involvement in the completion of the Human and other genome projects will help them participate in a similar role for the development of applications of converging technologies -particularly in nanomedicine. CONCLUSIONS: The proposed convergence will bring bridges between traditional disciplines. Particular attention should be placed on the ethical, legal, and social issues raised by the NBIC convergence. These technologies provide new directions for research and education in Biomedical Informatics placing a greater emphasis in multidisciplinary approaches.

Bioinformatics linkage of heterogeneous clinical and genomic information in support of personalized medicine.

OBJECTIVES: Biomedical Informatics as a whole faces a difficult epistemological task, since there is no foundation to explain the complexities of modeling clinical medicine and the many relationships between genotype, phenotype, and environment. This paper discusses current efforts to investigate such relationships, intended to lead to better diagnostic and therapeutic procedures and the development of treatments that could make personalized medicine a reality. METHODS: To achieve this goal there are a number of issues to overcome. Primary are the rapidly growing numbers of heterogeneous data sources which must be integrated to support personalized medicine. Solutions involving the use of domain driven information models of heterogeneous data sources are described in conjunction with controlled ontologies and terminologies. A number of such applications are discussed. RESULTS: Researchers have realized that many dimensions of biology and medicine aim to understand and model the informational mechanisms that support more precise clinical diagnostic, prognostic and therapeutic procedures. As long as data grows exponentially, novel Biomedical Informatics approaches and tools are needed to manage the data. Although researchers are typically able to manage this information within specific, usually narrow contexts of clinical investigation, novel approaches for both training and clinical usage must be developed. CONCLUSION: After some preliminary overoptimistic expectations, it seems clear now that genetics alone cannot transform medicine. In order to achieve this, heterogeneous clinical and genomic data source must be integrated in scientifically meaningful and productive systems. This will include hypothesis-driven scientific research systems along with well understood information systems to support such research. These in turn will enable the faster advancement of personalized medicine.

Using web services for linking genomic data to medical information systems.

OBJECTIVES: To develop a new perspective for biomedical information systems, regarding the introduction of ideas, methods and tools related to the new scenario of genomic medicine. METHODS: Technological aspects related to the analysis and integration of heterogeneous clinical and genomic data include mapping clinical and genetic concepts, potential future standards or the development of integrated biomedical ontologies. In this clinicomics scenario, we describe the use of Web services technologies to improve access to and integrate different information sources. We give a concrete example of the use of Web services technologies: the OntoFusion project. RESULTS: Web services provide new biomedical informatics (BMI) approaches related to genomic medicine. Customized workflows will aid research tasks by linking heterogeneous Web services. Two significant examples of these European Commission-funded efforts are the INFOBIOMED Network of Excellence and the Advancing Clinico-Genomic Trials on Cancer (ACGT) integrated project. CONCLUSIONS: Supplying medical researchers and practitioners with omics data and biologists with clinical datasets can help to develop genomic medicine. BMI is contributing by providing the informatics methods and technological infrastructure needed for these collaborative efforts.

An agent- and ontology-based system for integrating public gene, protein, and disease databases.

In this paper, we describe OntoFusion, a database integration system. This system has been designed to provide unified access to multiple, heterogeneous biological and medical data sources that are publicly available over Internet. Many of these databases do not offer a direct connection, and inquiries must be made via Web forms, returning results as HTML pages. A special module in the OntoFusion system is needed to integrate these public 'Web-based' databases. Domain ontologies are used to do this and provide database mapping and unification. We have used the system to integrate seven significant and widely used public biomedical databases: OMIM, PubMed, Enzyme, Prosite and Prosite documentation, PDB, SNP, and InterPro. A case study is detailed in depth, showing system performance. We analyze the system's architecture and methods and discuss its use as a tool for biomedical researchers.

Medical informatics and bioinformatics: integration or evolution through scientific crises?

OBJECTIVES: To contribute a new perspective on recent investigations into the scientific foundations of medical informatics (MI) and bioinformatics (BI). To support efforts that could generate synergies and new research directions. METHODS: MI and BI are compared and contrasted from a philosophy of science perspective. Historical examples from MI and BI are analyzed based on contrasting viewpoints about the evolution of scientific disciplines. RESULTS: Our analysis suggests that the scientific approaches of MI and BI involve different assumptions and foundations, which, together with largely non-overlapping communities of researchers for the two disciplines, have led to different courses of development. We indicate how their respective application domains, medicine, and biology may have contributed to these differences in development. CONCLUSIONS: An analysis from the point of view of the philosophy of science is characteristic of established scientific disciplines. From a Kuhnian perspective, both disciplines may be entering a period of scientific crisis, where their foundations are questioned and where new ideas (or paradigm shifts) and a progressive research programme are needed to advance them scientifically. We discuss research directions and trends both supporting and challenging integration of the subdisciplines of MI and BI into a unified field of biomedical informatics (BMI), centered around the evolution of information cybernetics.

Designing new methodologies for integrating biomedical information in clinical trials.

OBJECTIVES: To propose a modification to current methodologies for clinical trials, improving data collection and cost-efficiency. To describe a system to integrate distributed and heterogeneous medical and genetic databases for improving information access, retrieval and analysis of biomedical information. METHODS: Data for clinical trials can be collected from remote, distributed and heterogeneous data sources. In this distributed scenario, we propose an ontologybased approach, with two basic operations: mapping and unification. Mapping outputs the semantic model of a virtual repository with the information model of a specific database. Unification provides a single schema for two or more previously available virtual repositories. In both processes, domain ontologies can improve other traditional approaches. RESULTS: Private clinical databases and public genomic and disease databases (e.g., OMIM, Prosite and others) were integrated. We successfully tested the system using thirteen databases containing clinical and biological information and biomedical vocabularies. CONCLUSIONS: We present a domain-independent approach to biomedical database integration, used in this paper as a reference for the design of future models of clinico-genomic trials where information will be integrated, retrieved and analyzed. Such an approach to biomedical data integration has been one of the goals of the IST INFOBIOMED Network of Excellence in Biomedical Informatics, funded by the European Commission, and the new ACGT (Advanced Clinico-Genomic Trials on Cancer) project, where the authors will apply these methods to research experiments.

ONTOFUSION: ontology-based integration of genomic and clinical databases.

ONTOFUSION is an ontology-based system designed for biomedical database integration. It is based on two processes: mapping and unification. Mapping is a semi-automated process that uses ontologies to link a database schema with a conceptual framework-named virtual schema. There are three methodologies for creating virtual schemas, according to the origin of the domain ontology used: (1) top-down--e.g. using an existing ontology, such as the UMLS or Gene Ontology--, (2) bottom-up--building a new domain ontology-- and (3) a hybrid combination. Unification is an automated process for integrating ontologies and hence the database to which they are linked. Using these methods, we employed ONTOFUSION to integrate a large number of public genomic and clinical databases, as well as biomedical ontologies.

Grid requirements for the integration of biomedical information resources for health applications.

OBJECTIVES: The goal of this paper is to identify how Grid technology can be applied for the development and deployment of integration systems, bringing together distributed and heterogeneous biomedical information sources for medical applications. METHODS: The integration of new genetic and medical knowledge in clinical workflows requires the development of new paradigms for information management in which the ability to access and relate disparate data sources is essential. We adopt a requirements perspective based on the user needs we have identified in the development of the INFOGENMED system to assess current Grid technology against those requirements. RESULTS: The gap between Grid features and distributed biomedical information integration needs is characterized. Results from prospective studies are also reported. CONCLUSIONS: Grid infrastructures offer advanced features for the deployment of collaborative computational environments across virtual organizations. New Grid developments are in line with the problem of multiple site information integration. From the INFOGENMED point of view, Grid infrastructures need to evolve to implement structured data access services and semantic content description and discovery.

Bioinformatics: towards new directions for public health.

OBJECTIVES: Epidemiologists are reformulating their classical approaches to diseases by considering various issues associated to "omics" areas and technologies. Traditional differences between epidemiology and genetics include background, training, terminologies, study designs and others. Public health and epidemiology are increasingly looking forward to using methodologies and informatics tools, facilitated by the Bioinformatics community, for managing genomic information. Our aim is to describe which are the most important implications related with the increasing use of genomic information for public health practice, research and education. To review the contribution of bioinformatics to these issues, in terms of providing the methods and tools needed for processing genetic information from pathogens and patients. To analyze the research challenges in biomedical informatics related with the need of integration of clinical, environmental and genetic data and the new scenarios arisen in public health. METHODS: Review of the literature, Internet resources and material and reports generated by internal and external research projects. RESULTS: New developments are needed to advance in the study of the interactions between environmental agents and genetic factors involved in the development of diseases. The use of biomarkers, biobanks, and integrated genomic/clinical databases poses serious challenges for informaticians in order to extract useful information and knowledge for public health, biomedical research and healthcare. CONCLUSIONS: From an informatics perspective, integrated medical/biological ontologies and new semantic-based models for managing information provide new challenges for research in areas such as genetic epidemiology and the "omics" disciplines, among others. In this regard, there are various ethical, privacy, informed consent and social implications, that should be carefully addressed by researchers, practitioners and policy makers.