Daniel R. Masys

Use of keyword hierarchies to interpret gene expression patterns

MOTIVATIONnHigh-density microarray technology permits the quantitative and simultaneous monitoring of thousands of genes. The interpretation challenge is to extract relevant information from this large amount of data. A growing variety of statistical analysis approaches are available to identify clusters of genes that share common expression characteristics, but provide no information regarding the biological similarities of genes within clusters. The published literature provides a potential source of information to assist in interpretation of clustering results.nnnRESULTSnWe describe a data mining method that uses indexing terms (keywords) from the published literature linked to specific genes to present a view of the conceptual similarity of genes within a cluster or group of interest. The method takes advantage of the hierarchical nature of Medical Subject Headings used to index citations in the MEDLINE database, and the registry numbers applied to enzymes.

Giving Patients Access to Their Medical Records via the Internet: The PCASSO Experience

OBJECTIVEnThe Patient-Centered Access to Secure Systems Online (PCASSO) project is designed to apply state-of-the-art-security to the communication of clinical information over the Internet.nnnDESIGNnThe authors report the legal and regulatory issues associated with deploying the system, and results of its use by providers and patients. Human subject protection concerns raised by the Institutional Review Board focused on three areas-unauthorized access to information by persons other than the patient; the effect of startling or poorly understood information; and the effect of patient access to records on the record-keeping behavior of providers.nnnMEASUREMENTSnObjective and subjective measures of security and usability were obtained.nnnRESULTSnDuring its initial deployment phase, the project enrolled 216 physicians and 41 patients; of these, 68 physicians and 26 patients used the system one or more times. The system performed as designed, with no unauthorized information access or intrusions detected. Providers rated the usability of the system low because of the complexity of the secure login and other security features and restrictions limiting their access to those patients with whom they had a professional relationship. In contrast, patients rated the usability and functionality of the system favorably.nnnCONCLUSIONnHigh-assurance systems that serve both patients and providers will need to address differing expectations regarding security and ease of use.

PCASSO: a design for secure communication of personal health information via the internet

The Internet holds both promise and peril for the communications of person-identifiable health information. Because of technical features designed to promote accessibility and interoperability rather than security, Internet addressing conventions and transport protocols are vulnerable to compromise by malicious persons and programs. In addition, most commonly used personal computer (PC) operating systems currently lack the hardware-based system software protection and process isolation that are essential for ensuring the integrity of trusted applications. Security approaches designed for electronic commerce, that trade known security weaknesses for limited financial liability, are not sufficient for personal health data, where the personal damage caused by unintentional disclosure may be far more serious. To overcome these obstacles, we are developing and evaluating an Internet-based communications system called PCASSO (Patient-centered access to secure systems online) that applies state of the art security to health information. PCASSO includes role-based access control, multi-level security, strong device and user authentication, session-specific encryption and audit trails. Unlike Internet-based electronic commerce solutions, PCASSO secures data end-to-end: in the server; in the data repository; across the network; and on the client. PCASSO is designed to give patients as well as providers access to personal health records via the Internet.

2HAPI: a microarray data analysis system

SUMMARYn2HAPI (version 2 of High density Array Pattern Interpreter) is a web-based, publicly-available analytical tool designed to aid researchers in microarray data analysis. 2HAPI includes tools for searching, manipulating, visualizing, and clustering the large sets of data generated by microarray experiments. Other features include association of genes with NCBI information and linkage to external data resources. Unique to 2HAPI is the ability to retrieve upstream sequences of co-regulated genes for promoter analysis using MEME (Multiple Expectation-maximization for Motif Elicitation)nnnAVAILABILITYn2HAPI is freely available at http://array.sdsc.edu. Users can try 2HAPI anonymously with pre-loaded data or they can register as a 2HAPI user and upload their data.

Use of controlled terminology hierarchies to detect common characteristics of genes within expression clusters

Use of controlled terminology hierarchies to detect common characteristics of genes within expression clusters

Magnitude and specificity of temporal gene expression during HIV-1 infection of a CD4+ T cell

Magnitude and specificity of temporal gene expression during HIV-1 infection of a CD4+ T cellTRAIL is a member of the Tumour Necrosis Factor (TNF) Family and a potent inducer of apoptosis in many breast carcinoma cell lines but not in normal human mammary epithelial cells. In vivo administration of soluble TRAIL causes regression of breast cancer xenografts without causing measurable toxicity. Combining it with other traditional anti-cancer therapies enhances the efficacy of TRAIL treatment. The basis for the resistance of normal breast epithelial cells to TRAILinduced apoptosis will be investigated using filter arrays and high-density microarrays. Using a similar approach, the synergy between TRAIL and other cancer therapies will be studied.

PCASSO: Vanguard in Patient Empowerment

In 1996 the National Library of Medicine (NLM) funded a research project called Patient Centered Access to Secure Systems Online (PCASSO), which was proposed by Science Applications International Corporation (SAIC) in collaboration with the University of California, San Diego (UCSD). The project was designed to apply state-of-the-art security to the communication of clinical information over the Internet. At the project’s inception, several prototype Web-based clinical information systems existed,1–5 but all were explicitly designed for the benefit of health professionals—to enable them to view patient information stored on an enterprise server protected by a “firewall.” Further, most early Internet experiments simply attempted to duplicate existing care models and lines of communication using the new medium. The concept of enabling patients to view their own complete medical record over the Internet was considered by the liberal-minded as radical and by the traditionalists as completely insane. PCASSO was conceived with the premise that the full potential of the ubiquitous Internet lies in its potential to enable new channels of communication between providers and patients, and to empower patients with the knowledge they need to participate actively in their own care.