Bioinformatics

Research at NCTR

The National Center for Toxicological Research (NCTR) scientific core is the study of biochemical and molecular markers of health status using a systems-biology approach and emerging technologies, personalized nutrition and drug therapy to enhance human health, bioinformatics, and predictive technology development, neurotoxicology to include use of imaging techniques, risk-assessment methods, statistical modeling, and development of microbiological and chemical rapid-detection technologies to assure food safety and biosecurity. NCTR supports the Food and Drug Administration (FDA)’s mission to rapidly bring safe and efficacious products to the market and to reduce the risk of adverse-health effects from products on the market.

In support of many of our areas of research, genomic, proteomic, and bioinformatics approaches were developed or enhanced to allow for the identification of gene- and protein-expression profiles associated with neurotoxic events. For example, in studies on chemically induced mitochondrial dysfunction, significant increases in the gene expression of a specific uncoupling protein were demonstrated. Identification of such specific events can serve to elucidate mechanisms and provide markers of toxicity. A MicroPET imaging device was acquired and will provide the opportunity to follow such events noninvasively in longitudinal fashion, providing time-course information on lesion development, severity, and recovery.

The NCTR Center for Toxicoinformatics conducts research in bioinformatics and chemoinformatics and develops and coordinates informatics capabilities within NCTR, across FDA Centers, and in the larger toxicology community. The goal of the toxicoinformatics group is to develop methods for the analysis and integration of omics (genomics, transcriptomics, proteomics, and metabolomics) datasets. Bioinformatic tools created at NCTR include:

• ArrayTrack™ – DNA microarray data management, mining, analysis, and interpretation software
• MicroArray Quality Control (MAQC) Project – Development of microarray QC metrics and thresholds
• Endocrine Disruptor Knowledge Base (EDKB) Project – Resources to predict estrogen and androgen activity
• Decision Forest – A novel pattern recognition method for analysis of data from microarray experiments, proteomics research and predictive toxicology
• Mold2 – Software that generates molecular descriptors from two-dimensional structures