Biomedical subjects

Dan Casciano

Publications and source records attributed to Dan Casciano.

3 recordsLinked to original sources

PubMed2004

Development of public toxicogenomics software for microarray data management and analysis.

A robust bioinformatics capability is widely acknowledged as central to realizing the promises of toxicogenomics. Successful application of toxicogenomic approaches, such as DNA microarray, inextricably relies on appropriate data management, the ability to extract knowledge from massive amounts of data and the availability of functional information for data interpretation. At the FDA's National Center for Toxicological Research (NCTR), we are developing a public microarray data management and analysis software, called ArrayTrack. ArrayTrack is Minimum Information About a Microarray Experiment (MIAME) supportive for storing both microarray data and experiment parameters associated with a toxicogenomics study. A quality control mechanism is implemented to assure the fidelity of entered expression data. ArrayTrack also provides a rich collection of functional information about genes, proteins and pathways drawn from various public biological databases for facilitating data interpretation. In addition, several data analysis and visualization tools are available with ArrayTrack, and more tools will be available in the next released version. Importantly, gene expression data, functional information and analysis methods are fully integrated so that the data analysis and interpretation process is simplified and enhanced. ArrayTrack is publicly available online and the prospective user can also request a local installation version by contacting the authors.

Databases, Genetic↗

PubMed2004

Median-of-subsets normalization of intensities for cDNA array data.

cDNA arrays allow quantitative measurement of expression levels for thousands of genes simultaneously. The measurements are affected by many sources of variation, and substantial improvements in the precision of estimated effects accompany adjustments for these effects. Two generic nuisance variations, one associated with the magnitude of expression and the other associated with array location, are common in data from filter arrays. Procedures, like normalization using lowess regression, are effective at reducing variation associated with magnitude, and they have been widely adopted. However, variation associated with location has received less attention. Here, a simple, but effective method based on localized median is expounded for dealing with these nuisance effects, and its properties are discussed. The proposed methodology handles location-dependent variation ("splotches") and magnitude-dependent variation (background and/or saturation) effectively. The procedure is related to lowess when implemented to adjust magnitude-dependent variation, and it performs similarly. The proposed methodology is illustrated with data from the National Center for Toxicological Research (NCTR), where treatment differences in levels of mRNA from rat hepatocytes were assessed using 33P-labeled samples hybridized to cDNA spotted arrays. Normalizing intensities by the median-of-subsets removes systematic variation associated with the location of a gene on the array and/or the level of its expression. This procedure is easy to implement using iteratively reweighted least-squares algorithms. Although less sophisticated than lowess, this procedure works nearly as well for normalizing intensities based upon their magnitude. Unlike lowess, it can adjust for location-dependent effects.

DNA, Complementary↗

PubMed2003

ArrayTrack--supporting toxicogenomic research at the U.S. Food and Drug Administration National Center for Toxicological Research.

The mapping of the human genome and the determination of corresponding gene functions, pathways, and biological mechanisms are driving the emergence of the new research fields of toxicogenomics and systems toxicology. Many technological advances such as microarrays are enabling this paradigm shift that indicates an unprecedented advancement in the methods of understanding the expression of toxicity at the molecular level. At the National Center for Toxicological Research (NCTR) of the U.S. Food and Drug Administration, core facilities for genomic, proteomic, and metabonomic technologies have been established that use standardized experimental procedures to support centerwide toxicogenomic research. Collectively, these facilities are continuously producing an unprecedented volume of data. NCTR plans to develop a toxicoinformatics integrated system (TIS) for the purpose of fully integrating genomic, proteomic, and metabonomic data with the data in public repositories as well as conventional (Italic)in vitro(/Italic) and (Italic)in vivo(/Italic) toxicology data. The TIS will enable data curation in accordance with standard ontology and provide or interface a rich collection of tools for data analysis and knowledge mining. In this article the design, practical issues, and functions of the TIS are discussed through presenting its prototype version, ArrayTrack, for the management and analysis of DNA microarray data. ArrayTrack is logically constructed of three linked components: a) a library (LIB) that mirrors critical data in public databases; b) a database (MicroarrayDB) that stores microarray experiment information that is Minimal Information About a Microarray Experiment (MIAME) compliant; and c) tools (TOOL) that operate on experimental and public data for knowledge discovery. Using ArrayTrack, we can select an analysis method from the TOOL and apply the method to selected microarray data stored in the MicroarrayDB; the analysis results can be linked directly to gene information in the LIB.

Databases, Factual↗