The ontology of craniofacial development and malformation for translational craniofacial research.

We introduce the Ontology of Craniofacial Development and Malformation (OCDM) as a mechanism for representing knowledge about craniofacial development and malformation, and for using that knowledge to facilitate integrating craniofacial data obtained via multiple techniques from multiple labs and at multiple levels of granularity. The OCDM is a project of the NIDCR-sponsored FaceBase Consortium, whose goal is to promote and enable research into the genetic and epigenetic causes of specific craniofacial abnormalities through the provision of publicly accessible, integrated craniofacial data. However, the OCDM should be usable for integrating any web-accessible craniofacial data, not just those data available through FaceBase. The OCDM is based on the Foundational Model of Anatomy (FMA), our comprehensive ontology of canonical human adult anatomy, and includes modules to represent adult and developmental craniofacial anatomy in both human and mouse, mappings between homologous structures in human and mouse, and associated malformations. We describe these modules, as well as prototype uses of the OCDM for integrating craniofacial data. By using the terms from the OCDM to annotate data, and by combining queries over the ontology with those over annotated data, it becomes possible to create "intelligent" queries that can, for example, find gene expression data obtained from mouse structures that are precursors to homologous human structures involved in malformations such as cleft lip. We suggest that the OCDM can be useful not only for integrating craniofacial data, but also for expressing new knowledge gained from analyzing the integrated data.

Spatial-symbolic Query Engine in Anatomy.

OBJECTIVES: Currently, the primary means for answering anatomical questions such as 'what vital organs would potentially be impacted by a bullet wound to the abdomen?' is to look them up in textbooks or to browse online sources. In this work we describe a semantic web service and spatial query processor that permits a user to graphically pose such questions as joined queries over separately defined spatial and symbolic knowledge sources. METHODS: Spatial relations (e.g. anterior) were defined by two anatomy experts, and based on a 3-D volume of labeled images of the thorax, all the labeled anatomical structures were queried to retrieve the target structures for every query structure and every spatial relation. A web user interface and a web service were designed to relate existing symbolic information from the Foundational Model of Anatomy ontology (FMA) with spatial information provided by the spatial query processor, and to permit users to select anatomical structures and define queries. RESULTS: We evaluated the accuracy of results returned by the queries, and since there is no independent gold standard, we used two anatomy experts' opinions as the gold standard for comparison. We asked the same experts to define the gold standard and to define the spatial relations. The F-measure for the overall evaluation is 0.90 for rater 1 and 0.56 for rater 2. The percentage of observed agreement is 99% and Cohen's kappa coefficient reaches 0.51. The main source of disagreement relates to issues with the labels used in the dataset, and not with the tool itself. CONCLUSIONS: In its current state the system can be used as an end-user application but it is likely to be of most use as a framework for building end-user applications such as displaying the results as a 3-D anatomical scene. The system promises potential practical utility for obtaining and navigating spatial and symbolic data.

Commentaries on "Informatics and medicine: from molecules to populations".

OBJECTIVE: To discuss interdisciplinary research and education in the context of informatics and medicine by commenting on the paper of Kuhn et al. "Informatics and Medicine: From Molecules to Populations". METHOD: Inviting an international group of experts in biomedical and health informatics and related disciplines to comment on this paper. RESULTS AND CONCLUSIONS: The commentaries include a wide range of reasoned arguments and original position statements which, while strongly endorsing the educational needs identified by Kuhn et al., also point out fundamental challenges that are very specific to the unusual combination of scientific, technological, personal and social problems characterizing biomedical informatics. They point to the ultimate objectives of managing difficult human health problems, which are unlikely to yield to technological solutions alone. The psychological, societal, and environmental components of health and disease are emphasized by several of the commentators, setting the stage for further debate and constructive suggestions.

A model browser for biosimulation.

The complexities of biological simulation present difficulties with modeling and experimenting. Simulators process models represented as code, whereas biologists think about abstract models. Our ModelBrowser addresses this difficulty through interactive visualization. Variables and equations appear as a directed graph of nodes and edges, and the user can search and browse this graph by performing queries on metadata associated with the variables and the connectivity of the edges. The browser also supports a hierarchical categorization of the variables, such as by an ontology. We believe that the ModelBrowser will help biologists reason about code in the context of the abstract model, so that they can understand and modify others' code and debug their own.

BioMediator data integration: beyond genomics to neuroscience data.

The BioMediator system developed at the University of Washington (UW) provides a theoretical and practical foundation for data integration across diverse biomedical research domains and various data types. In this paper we demonstrate the generalizability of its architecture through its application to the UW Human Brain Project (HBP) for understanding language organization in the brain. We first describe the system architecture and the characteristics of the four data sources developed by the UW HBP. Second we present the process of developing the application prototype for HBP neuroscience researchers posing queries across these semantically and syntactically heterogeneous neurophysiologic data sources. Then we discuss the benefits and potential limitations of the BioMediator system as a general data integration solution for different user groups in genomic and neuroscience research domains.

A pilot bridging data integration and analytics: BioMediator and R?

Biological research today involves aggregating and analyzing large amounts of data from disparate sources. Tools such as the University of Washington's BioMediator system integrate heterogeneous data. Analytic packages such as the R environment have a rich set of tools to analyze biomedical research data. Our pilot project bridged data integration and analytics in a general way by successfully incorporating the BioMediator system into the R platform for specific analyses on neurophysiologic research data.

Profile of on-line anatomy information resources: design and instructional implications.

This study is based on a review of 40 on-line anatomy web resources compiled from sites selected from our own searches as well as sites reviewed and published by an external group (Voiglio et al., 1999, Surg. Radiol. Anat. 21:65-68; Frasca et al., 2000, Surg. Radiol. Anat. 22:107-110). The purpose of our survey was to propose criteria by which anatomy educators could judge the characteristics of the currently available web-based resources for incorporation into the courses they teach. Each site was reviewed and scored based on a survey matrix that included four main categories: 1). site background information, 2). content components, 3). interactivity features, and 4). user interface design components. The average score of the reviewed sites was 3.3 of the total possible score of 10, indicating the limited use of computer-based design features by the majority of sites. We found, however, a number of programs in each of the survey categories that could serve as prototypes for designing future on-line anatomy resources. From the survey we conclude that various design features are less important than the comprehensiveness, depth, and logical organization of content. We suggest that the content should be sufficient for supporting explicitly defined educational objectives, which should target specific end-user populations. The majority of anatomy programs currently accessible on-line fall short of these requirements. There is a need for a coordinated and synergistic effort to generate a comprehensive anatomical information resource that is of sufficient quality and depth to support higher levels of learning beyond the memorization of structure names. Such a resource is a prerequisite for meaningful on-line anatomy education.

Imaging and the Human Brain Project: a review.

OBJECTIVES: Survey current work primarily funded by the US Human Brain Project (HBP) that involves substantial use of images. Organize this work around a framework based on the physical organization of the body. METHODS: Pointers to individual research efforts were obtained through the HBP home page as well as personal contracts from HBP annual meetings. References from these sources were followed to find closely related work. The individual research efforts were then studied and characterized. RESULTS: The subject of the review is the intersection of neuroinformatics (information about the brain), imaging informatics (information about images), and structural informatics (information about the physical structure of the body). Of the 30 funded projects currently listed on the HBP web site, at least 22 make heavy use of images. These projects are described in terms of broad categories of structural imaging, functional imaging, and image-based brain information systems. CONCLUSIONS: Understanding the most complex entity known (the brain) gives rise to many interesting and difficult problems in informatics and computer science. Although much progress has been made by HBP and other neuroinformatics researchers, a great many problems remain that will require substantial informatics research efforts. Thus, the HPB can and should be seen as an excellent driving application area for biomedical informatics research.

The Virtual Anatomy Lab: a hands-on anatomy learning environment.

This paper introduces the Virtual Anatomy Lab software platform for coordinating on-line gross anatomy learning sessions over time.

Enabling clinicians, researchers, and educators to build custom web-based biomedical information systems.

We describe an open-source toolkit that enables clinicians, researchers, and educators to build their own web-based biomedical information systems. The Web Interfacing Repository Manager (Wirm) is a high-level application server aimed at medical professionals, allowing them to create individually tailored systems for managing their multimedia data and knowledge. We provide an overview of the features of Wirm, explaining how they meet the requirements for supporting biomedical information management, and describe four applications that are currently being developed with Wirm: MyPACS, a teaching file authoring system for radiologists, Fathom, an experiment management system for natural language processing, the Digital Anatomist Repository, an image archiving tool for medical schools, and Ontolog, a browser for medical vocabularies.

IML: An image markup language.

Image Markup Language is an extensible markup language (XML) schema used to describe both image metadata and annotations. It describes both data pertaining to an entire image, and data that are tied to specific regions or features of the image. Developed for a specific domain in Medical Education, this pa-per describes extensions to take advantage of the Dublin Core metadata standard, and of an XML schema for vector graphics representation. We have developed a prototype system of open source tools implementing an authoring system, a client system, and an image annotation database which can be queried though the Web.

Foundational model of neuroanatomy: implications for the Human Brain Project.

In order to meet the need for a controlled terminology in neuroinformatics, we have integrated the extensive terminology of NeuroNames into the Foundational Model of anatomy. We illustrate the application of foundational principles for the establishment of an inheritance hierarchy, which accommodates anatomical attributes of neuroanatomical concepts and provides the foundation to which other information may be linked.

Server-based approach to web visualization of integrated 3-D medical image data.

Although computer processing power and network bandwidth are rapidly increasing, the average desktop is still not able to rapidly process large datasets such as 3-D medical image volumes. We have therefore developed a server side approach to this problem, in which a high performance graphics server accepts commands from web clients to load, process and render 3-D image volumes and models. The renderings are saved as 2-D snapshots on the server, where they are uploaded and displayed on the client. User interactions with the graphic interface on the client side are translated into additional commands to manipulate the 3-D scene, after which the server re-renders the scene and sends a new image to the client. Example forms-based and Java-based clients are described for a brain mapping application, but the techniques should be applicable to multiple domains where 3-D medical image visualization is of interest.

Requirements of a Web-based experiment management system.

Recent advances in tools for scientific data acquisition, visualization, and analysis have lead to growing information management problems for medical research laboratories. An exponential increase in the volume of data, combined with a proliferation of heterogeneous formats and autonomous systems, has driven the need for flexible and powerful Experiment Management Systems (EMS). This paper provides a detailed analysis of the informatics requirements of an EMS, and proposes a new type of middleware called an EMS-Building Environment (EMSBE), which enables the rapid development of web-based systems for managing laboratory data and workflow. We describe the Web-Interfacing Respository Manager (WIRM), an open-source application server for building customizable experiment management systems. WIRM is being used to manage several ongoing experiments, including a natural language processor of radiological findings, and an interdisciplinary project for studying brain function.

Anatomical information in radiation treatment planning.

We report on experience and insights gained from prototyping, for clinical radiation oncologists, a new access tool for the University of Washington Digital Anatomist information resources. This access tool is designed to integrate with a radiation therapy planning (RTP) system in use in a clinical setting. We hypothesize that the needs of practitioners in a clinical setting are different from the needs of students, the original targeted users of the Digital Anatomist system, but that a common knowledge resource can serve both. Our prototype was designed to help define those differences and study the feasibility of a full anatomic reference system that will support both clinical radiation therapy and all the existing educational applications.

Integration and visualization of multimodality brain data for language mapping.

A goal of the University of Washington Brain Project is to develop software tools for processing, integrating and visualizing multimodality language data obtained at the time of neurosurgery, both for surgical planning and for the study of language organization in the brain. Data from a single patient consist of four magnetic resonance-based image volumes, showing anatomy, veins, arteries and functional activation (fMRI). The data also include the location, on the exposed cortical surface, of sites that were electrically stimulated for the presence of language. These five sources are mapped to a common MR-based neuroanatomical model, then visualized to gain a qualitative appreciation of their relationships, prior to quantitative analysis. These procedures are described and illustrated, with emphasis on the visualization of fMRI activation, which may be deep in the brain, with respect to surface-based stimulation sites.

Design features of on-line anatomy information resources: a comparison with the Digital Anatomist.

In order to update the design of the next generation of the Digital Anatomist, we have surveyed teaching assistants who have used the Digital Anatomist for learning and teaching anatomy as medical students, and have also examined available anatomy web sites with sufficient content to support learning. The majority of web sites function in an atlas mode and provide for the identification of structures. These atlases incorporate a variety of features for interactivity with 2D images, some of which are not available in the Digital Anatomist. The surveys suggest that the greatest need is for on-line access to comprehensive and detailed anatomical information and for the development of knowledge-based methods that allow the direct manipulation of segmented 3D graphical models by the user. The requirement for such interactivity is a comprehensive symbolic model of the physical organization of the body that can support inference.

Semi-automatic scene generation using the Digital Anatomist Foundational Model.

A recent survey shows that a major impediment to more widespread use of computers in anatomy education is the inability to directly manipulate 3-D models, and to relate these to corresponding textual information. In the University of Washington Digital Anatomist Project we have developed a prototype Web-based scene generation program that combines the symbolic Foundational Model of Anatomy with 3-D models. A Web user can browse the Foundational Model (FM), then click to request that a 3-D scene be created of an object and its parts or branches. The scene is rendered by a graphics server, and a snapshot is sent to the Web client. The user can then manipulate the scene, adding new structures, deleting structures, rotating the scene, zooming, and saving the scene as a VRML file. Applications such as this, when fully realized with fast rendering and more anatomical content, have the potential to significantly change the way computers are used in anatomy education.

Functional roles of Broca's area and SMG: evidence from cortical stimulation mapping in a deaf signer.

The importance of the left hemisphere in language function has been firmly established and current work strives to understand regional specializations within the perisylvian language areas. This paper reports a case study of a deaf user of American Sign Language undergoing an awake cortical stimulation mapping procedure. Patterns of sign errors accompanying electrical stimulation of Broca's area and the supramarginal gyrus (SMG) are reported. Our findings show Broca's area to be involved in the motor execution of sign language. These data demonstrate that the linguistic specificity of Broca's area is not limited to speech behavior. In addition, unusual semantic-phonological errors were observed with stimulation to the SMG; these data may implicate the SMG in the binding of linguistic features in the service of language production. Taken together, these findings provide important insight into the linguistic specificity of Broca's area and the functional role of the supramarginal gyrus in language processing.