ArrayTrack - Supporting Toxicogenomic Research at the U.S. Food and Drug Administration National Center for Toxicological Research

Abstract

While modern toxicology has focused on understanding biological mechanisms involved in the expression of toxicity at the molecular level, a technological revolution has occurred enabling researchers to perform experiments on a scale of unprecedented proportions (Marshall and Hodgson 1998; Ramsay 1998). Highthroughput experimentation is producing large amounts of data impossible to analyze without informatics-related support (Bellenson 1999; Spengler 2000). We see a paradigm shift in toxicology research, where hypothesis-driven research is complemented by data-driven experimentation designed to be hypothesis generating (Afshari et al. 1999). Although toxicogenomics, the study of toxicology using highthroughput "omics" technologies (Aardema and MacGregor 2002; Hamadeh et al. 2002; Nuwaysir et al. 1999; Schmidt 2002; Ulrich and Friend 2002), and systems toxicology, the study of toxicology through data integration (Waters et al. 2003), have advanced rapidly and are likely to continue to advance, development of software infrastructures to manage, analyze, and integrate the diverse data has lagged behind. Recently, Waters et al. (2003) proposed a conceptual framework of chemical effects in biological systems [(CEBS) Chemical Effects in Biological Systems knowledge base] to meet the expanding toxicogenomic research needs at the National Center for Toxicogenomics (NCT) (Tennant 2002), including both NCT intramural research and research within the Toxicogenomics Research Consortium (TRC) (Medlin 2002). Both the NCT and the TRC are located at the National Institute of Environmental Health Sciences (NIEHS) in the Research Triangle Park, North Carolina. Implementing toxicogenomic technologies is a high-priority initiative at the U.S. Food and Drug Administration (U.S. FDA) National Center for Toxicological Research (NCTR). A microarray core facility using validated and standardized protocols has been established. Similar facilities for Methods ArrayTrack contains three integrated components: a) MicroarrayDB, which stores essential data associated with a

Unsupervised Selection of Highly Coexpressed and Noncoexpressed Genes Using a Consensus Clustering Approach

“…The format of each cell is "number of selected genes⏐corresponding number of patterns⏐accuracy." clusters using ArrayTrack (Tong et al, 2003). Table 6 displays some significant pathways with p-value less than 0.05.…”

Classification of cDNA Array Genes That Have a Highly Significant Discriminative Power Due to Their Unique Distribution in Four Brain Regions

“…The intensities at all the array probe sites captured on the phosphor image were initially quantified using AtlasImage 2.01 software provided by Clontech). These intensity data were loaded into ArrayTrack (Tong et al, 2003a(Tong et al, , 2003b. For all the arrays analyzed in these experiments, individual spot intensities were log10 transformed and the mean log10 intensity of all genes in the array was subtracted for each spot as mean-zero global normalization.…”

Untitled

“…The median fluorescence intensity of all the pixels within one feature was taken as the intensity value for that feature. All the raw data were imported into ArrayTrack Software [10] and were normalized using LOWESS Normalization with background subtraction. The data correlation values were computed with JMP 6.0 software (SAS, Inc., Cary, NC).…”