Mining connections between chemicals, proteins, and diseases extracted from Medline annotations.

The biomedical literature is an important source of information about the biological activity and effects of chemicals. We present an application that extracts terms indicating biological activity of chemicals from Medline records, associates them with chemical name and stores the terms in a repository called ChemoText. We describe the construction of ChemoText and then demonstrate its utility in drug research by employing Swanson's ABC discovery paradigm. We reproduce Swanson's discovery of a connection between magnesium and migraine in a novel approach that uses only proteins as the intermediate B terms. We validate our methods by using a cutoff date and evaluate them by calculating precision and recall. In addition to magnesium, we have identified valproic acid and nitric oxide as chemicals which developed links to migraine. We hypothesize, based on protein annotations, that zinc and retinoic acid may play a role in migraine. The ChemoText repository has promise as a data source for drug discovery.

Ultra-Structure database design methodology for managing systems biology data and analyses.

BACKGROUND: Modern, high-throughput biological experiments generate copious, heterogeneous, interconnected data sets. Research is dynamic, with frequently changing protocols, techniques, instruments, and file formats. Because of these factors, systems designed to manage and integrate modern biological data sets often end up as large, unwieldy databases that become difficult to maintain or evolve. The novel rule-based approach of the Ultra-Structure design methodology presents a potential solution to this problem. By representing both data and processes as formal rules within a database, an Ultra-Structure system constitutes a flexible framework that enables users to explicitly store domain knowledge in both a machine- and human-readable form. End users themselves can change the system's capabilities without programmer intervention, simply by altering database contents; no computer code or schemas need be modified. This provides flexibility in adapting to change, and allows integration of disparate, heterogenous data sets within a small core set of database tables, facilitating joint analysis and visualization without becoming unwieldy. Here, we examine the application of Ultra-Structure to our ongoing research program for the integration of large proteomic and genomic data sets (proteogenomic mapping). RESULTS: We transitioned our proteogenomic mapping information system from a traditional entity-relationship design to one based on Ultra-Structure. Our system integrates tandem mass spectrum data, genomic annotation sets, and spectrum/peptide mappings, all within a small, general framework implemented within a standard relational database system. General software procedures driven by user-modifiable rules can perform tasks such as logical deduction and location-based computations. The system is not tied specifically to proteogenomic research, but is rather designed to accommodate virtually any kind of biological research. CONCLUSION: We find Ultra-Structure offers substantial benefits for biological information systems, the largest being the integration of diverse information sources into a common framework. This facilitates systems biology research by integrating data from disparate high-throughput techniques. It also enables us to readily incorporate new data types, sources, and domain knowledge with no change to the database structure or associated computer code. Ultra-Structure may be a significant step towards solving the hard problem of data management and integration in the systems biology era.

Comparison of navigation techniques for large digital images.

Medical images are examined on computer screens in a variety of contexts. Frequently, these images are larger than computer screens, and computer applications support different paradigms for user navigation of large images. The paper reports on a systematic investigation of what interaction techniques are the most effective for navigating images larger than the screen size for the purpose of detecting small image features. An experiment compares five different types of geometrically zoomable interaction techniques, each at two speeds (fast and slow update rates) for the task of finding a known feature in the image. There were statistically significant performance differences between several groupings of the techniques. The fast versions of the ArrowKey, Pointer, and ScrollBar performed the best. In general, techniques that enable both intuitive and systematic searching performed the best at the fast speed, while techniques that minimize the number of interactions with the image were more effective at the slow speed. Additionally, based on a postexperiment questionnaire and qualitative comparison, users expressed a clear preference for the Pointer technique, which allowed them to more freely and naturally interact with the image.

Decoupling the scholarly journal.

Although many observers have advocated the reform of the scholarly publishing system, improvements to functions like peer review have been adopted sluggishly. We argue that this is due to the tight coupling of the journal system: the system's essential functions of archiving, registration, dissemination, and certification are bundled together and siloed into tens of thousands of individual journals. This tight coupling makes it difficult to change any one aspect of the system, choking out innovation. We suggest that the solution is the "decoupled journal (DcJ)." In this system, the functions are unbundled and performed as services, able to compete for patronage and evolve in response to the market. For instance, a scholar might deposit an article in her institutional repository, have it copyedited and typeset by one company, indexed for search by several others, self-marketed over her own social networks, and peer reviewed by one or more stamping agencies that connect her paper to external reviewers. The DcJ brings publishing out of its current seventeenth-century paradigm, and creates a Web-like environment of loosely joined pieces-a marketplace of tools that, like the Web, evolves quickly in response to new technologies and users' needs. Importantly, this system is able to evolve from the current one, requiring only the continued development of bolt-on services external to the journal, particularly for peer review.

A curricula-based comparison of biomedical and health informatics programs in the USA.

OBJECTIVE: The field of Biomedical and Health Informatics (BMHI) continues to define itself, and there are many educational programs offering 'informatics' degrees with varied foci. The goal of this study was to develop a scheme for systematic comparison of programs across the entire BMHI spectrum and to identify commonalities among informatics curricula. DESIGN: Guided by several published competency sets, a grounded theory approach was used to develop a program/curricula categorization scheme based on the descriptions of 636 courses offered by 73 public health, nursing, health, medical, and bioinformatics programs in the USA. The scheme was then used to compare the programs in the aforementioned five informatics disciplines. RESULTS: The authors developed a Course-Based Informatics Program Categorization (CBIPC) scheme that can be used both to classify coursework for any BMHI educational program and to compare programs from the same or related disciplines. The application of CBIPC scheme to the analysis of public health, nursing, health, medical, and bioinformatics programs reveals distinct intradisciplinary curricular patterns and a common core of courses across the entire BMHI education domain. Limitations The study is based on descriptions of courses from the university's webpages. Thus, it is limited to sampling courses at one moment in time, and classification for the coding scheme is based primarily on course titles and course descriptions. CONCLUSION: The CBIPC scheme combines empirical data about educational curricula from diverse informatics programs and several published competency sets. It also provides a foundation for discussion of BMHI education as a whole and can help define subdisciplinary competencies.

TAMAL: an integrated approach to choosing SNPs for genetic studies of human complex traits.

UNLABELLED: Investigators conducting studies of the molecular genetics of complex traits in humans often need rationally to select a set of single nucleotide polymorphisms (SNPs) from the hundreds or thousands available for a candidate gene. Accomplishing this requires integration of genomic data from distributed databases and is both time-consuming and error-prone. We developed the TAMAL (Technology And Money Are Limiting) web site to help identify promising SNPs for further investigation. For a given list of genes, TAMAL identifies SNPs that meet user-specified criteria (e.g. haplotype tagging SNPs or SNP predicted to lead to amino acid changes) from current versions of online resources (i.e. HapMap, Perlegen, Affymetrix, dbSNP and the UCSC genome browser). AVAILABILITY: TAMAL is a platform independent web-based application available free of charge at http://neoref.ils.unc.edu/tamal. SUPPLEMENTARY INFORMATION: http://neoref.ils.unc.edu/tamal/.

Assessment of real-time 3D visualization for cardiothoracic diagnostic evaluation and surgery planning.

RATIONALE AND OBJECTIVES: Three-dimensional (3D) real-time volume rendering has demonstrated improvements in clinical care for several areas of radiological imaging. We test whether advanced real-time rendering techniques combined with an effective user interface will allow radiologists and surgeons to improve their performance for cardiothoracic surgery planning and diagnostic evaluation. MATERIAL AND METHODS: An interactive combination 3D and 2D visualization system developed at the University of North Carolina at Chapel Hill was compared against standard tiled 2D slice presentation on a viewbox. The system was evaluated for 23 complex cardiothoracic computed tomographic (CT) cases including heart-lung and lung transplantation, tumor resection, airway stent placement, repair of congenital heart defects, aortic aneurysm repair, and resection of pulmonary arteriovenous malformation. Radiologists and surgeons recorded their impressions with and without the use of the interactive visualization system. RESULTS: The cardiothoracic surgeons reported positive benefits to using the 3D visualizations. The addition of the 3D visualization changed the surgical plan (65% of cases), increased the surgeon's confidence (on average 40% per case), and correlated well with the anatomy found at surgery (95% of cases). The radiologists reported fewer and less major changes than the surgeons in their understanding of the case due to the 3D visualization. They found new findings or additional information about existing findings in 66% of the cases; however, they changed their radiology report in only 14% of the cases. CONCLUSION: With the appropriate choice of 3D real-time volume rendering and a well-designed user interface, both surgeons and radiologists benefit from viewing an interactive 3D visualization in addition to 2D images for surgery planning and diagnostic evaluation of complex cardiothoracic cases. This study finds that 3D visualization is especially helpful to the surgeon in understanding the case, and in communicating and planning the surgery. These results suggest that including real-time 3D visualization would be of clinical benefit for complex cardiothoracic CT cases.

Soft copy display requirements for digital mammography.

One of the advantages of digital mammography is to display mammograms on softcopy (electronic displays). Softcopy display of mammography is challenging because of the spatial and contrast resolution demands present in mammograms. We have designed and developed a softcopy mammography display application, Mammoview, which is capable of allowing radiologists to read mammograms as quickly and as accurately as they can on film alternators. We review the studies using Mammoview to elucidate the requirements of a successful softcopy display station. The design and development of the Mammoview softcopy display station are described in this article, and results of several studies using Mammoview are reported, including subjective feedback from Radiological Society of North America (RSNA) conference demonstrations, and clinical studies measuring performance in terms of speed and accuracy. Additional analysis of user interactions and user feedback is used to study the successes and shortcomings of mammography display stations like Mammoview. Overall, radiologist readings using Mammoview have been shown to be as fast and as accurate as readings using mammography film alternators. However, certain parts of the softcopy interface were more successful than their film counterparts, whereas others were less successful. Data analysis of the recorded human-computer interactions for the softcopy component of the clinical trial indicate statistically significant correlations between the difference in review time of softcopy versus alternator readings and three factors: the number of interactions, the reader, and the size of the image being reviewed. The first factor (number of interactions) suggests that simpler interfaces require less time to use; the second factor, the reader, supports previous findings that radiologists vary in how fast they read screening mammography studies; the third, size of image, suggests that the speed of softcopy review is increased relative to film readings when images are significantly larger than the display size. Feedback from radiologists using the system in clinical trials and at demonstration exhibits at RSNA indicated good acceptance of the interface and easy adaptation. Radiologists indicated that they felt comfortable using the interface, and that they would use such a softcopy interface in clinical practice. Finally, preliminary work suggests that the addition of a simple interaction to incorporate computer-aided detection (CAD) results would improve reading accuracy without significantly increasing reader times.

Interpretation of digital mammograms: comparison of speed and accuracy of soft-copy versus printed-film display.

PURPOSE: To compare the speed and accuracy of the interpretations of digital mammograms by radiologists by using printed-film versus soft-copy display. MATERIALS AND METHODS: After being trained in interpretation of digital mammograms, eight radiologists interpreted 63 digital mammograms, all with old studies for comparison. All studies were interpreted by all readers in soft-copy and printed-film display, with interpretations of images in the same cases at least 1 month apart. Mammograms were interpreted in cases that included six biopsy-proved cancers and 20 biopsy-proved benign lesions, 20 cases of probably benign findings in patients who underwent 6-month follow-up, and 17 cases without apparent findings. Area under the receiver operating characteristic curve (A(z)), sensitivity, and specificity were calculated for soft-copy and printed-film display. RESULTS: There was no significant difference in the speed of interpretation, but interpretations with soft-copy display were slightly faster. The differences in A(z), sensitivity, and specificity were not significantly different; A(z) and sensitivity were slightly better for interpretations with printed film, and specificity was slightly better for interpretations with soft copy. CONCLUSION: Interpretation with soft-copy display is likely to be useful with digital mammography and is unlikely to significantly change accuracy or speed.