Using Petri Net tools to study properties and dynamics of biological systems.

Petri Nets (PNs) and their extensions are promising methods for modeling and simulating biological systems. We surveyed PN formalisms and tools and compared them based on their mathematical capabilities as well as by their appropriateness to represent typical biological processes. We measured the ability of these tools to model specific features of biological systems and answer a set of biological questions that we defined.

A statistical approach to scanning the biomedical literature for pharmacogenetics knowledge.

Objective: Biomedical databases summarize current scientific knowledge, but they generally require years of laborious curation effort to build, focusing on identifying pertinent literature and data in the voluminous biomedical literature. It is difficult to manually extract useful information embedded in the large volumes of literature, and automated intelligent text analysis tools are becoming increasingly essential to assist in these curation activities. The goal of the authors was to develop an automated method to identify articles in Medline citations that contain pharmacogenetics data pertaining to gene-drug relationships.

A resource to acquire and summarize pharmacogenetics knowledge in the literature.

To determine how genetic variations contribute the variations in drug response, we need to know the genes that are related to drugs of interest. But there are no publicly available data-bases of known gene-drug relationships, and it is time-consuming to search the literature for this information. We have developed a resource to support the storage, summarization, and dissemination of key gene-drug interactions of relevance to pharmacogenetics.

Using a Bayesian network to predict the probability and type of breast cancer represented by microcalcifications on mammography.

Since the widespread adoption of mammographic screening in the 1980's there has been a significant increase in the detection and biopsy of both benign and malignant microcalcifications. Though current practice standards recommend that the positive predictive value (PPV) of breast biopsy should be in the range of 25-40%, there exists significant variability in practice. Microcalcifications, if malignant, can represent either a non-invasive or an invasive form of breast cancer.

Metastatic breast cancer in a 54-year-old woman: integrative treatment with yttrium-90 radioembolization.

In 1993, a 54-year-old woman was diagnosed with early-stage breast adenocarcinoma and treated with doxorubicin and cyclophosphamide followed by tamoxifen. Nine years later, the patient presented for integrative treatment, with liver metastases. Carcinoembryonic antigen was significantly elevated.

Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects.

Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, DeltaF508, results in the production of a misfolded CFTR protein that is retained in the endoplasmic reticulum and targeted for degradation. Curcumin is a nontoxic Ca-adenosine triphosphatase pump inhibitor that can be administered to humans safely.

A probabilistic expert system that provides automated mammographic-histologic correlation: initial experience.

Objective: We sought to determine whether a probabilistic expert system can provide accurate automated imaging-histologic correlations to aid radiologists in assessing the concordance of mammographic findings with the results of imaging-guided breast biopsies.

Materials And Methods: We created a Bayesian network in which Breast Imaging Reporting and Data System (BI-RADS) descriptors are used to convey the level of suspicion of mammographic abnormalities. Our system is a computer model that links BI-RADS descriptors with diseases of the breast using probabilities derived from the literature.

Hepatic MR imaging with ferumoxides: multicenter study of safety and effectiveness of direct injection protocol.

Purpose: To compare the safety and effectiveness of an undiluted direct injection of ferumoxides with those of a diluted slow infusion of ferumoxides during 30 minutes in patients with known liver lesions or in those suspected of having them.

Materials And Methods: Two hundred thirty-three patients at 16 institutions were randomized to receive either an undiluted direct injection of 0.56 mg of iron per kilogram of body weight of ferumoxides administered during 2 minutes (2 mL/min) or a diluted slow infusion administered during 30 minutes.

Representing genetic sequence data for pharmacogenomics: an evolutionary approach using ontological and relational models.

Motivation: The information model chosen to store biological data affects the types of queries possible, database performance, and difficulty in updating that information model. Genetic sequence data for pharmacogenetics studies can be complex, and the best information model to use may change over time. As experimental and analytical methods change, and as biological knowledge advances, the data storage requirements and types of queries needed may also change.

Automating data acquisition into ontologies from pharmacogenetics relational data sources using declarative object definitions and XML.

Ontologies are useful for organizing large numbers of concepts having complex relationships, such as the breadth of genetic and clinical knowledge in pharmacogenomics. But because ontologies change and knowledge evolves, it is time consuming to maintain stable mappings to external data sources that are in relational format. We propose a method for interfacing ontology models with data acquisition from external relational data sources.

Ontology development for a pharmacogenetics knowledge base.

Research directed toward discovering how genetic factors influence a patient's response to drugs requires coordination of data produced from laboratory experiments, computational methods, and clinical studies. A public repository of pharmacogenetic data should accelerate progress in the field of pharmacogenetics by organizing and disseminating public datasets. We are developing a pharmacogenetics knowledge base (PharmGKB) to support the storage and retrieval of both experimental data and conceptual knowledge.

PharmGKB: the Pharmacogenetics Knowledge Base.

The Pharmacogenetics Knowledge Base (PharmGKB; http://www.pharmgkb.org/) contains genomic, phenotype and clinical information collected from ongoing pharmacogenetic studies.