Computational systems analysis of developmental toxicity: design, development and implementation of a Birth Defects Systems Manager (BDSM)

Birth defects and developmental disabilities remain an important public health issue worldwide. With the availability of genomic sequences from a growing number of human and model organisms and the rapid expansion of the public repositories holding large-scale gene expression datasets, a computational systems analysis of developmental toxicology can incorporate this vast digital information toward the realization of predictive models for complex disease. Here we describe the initial design, development and implementation of a Birth Defects Systems Manager (BDSM). The project was motivated by the need for a computational-bioinformatics infrastructure to manage vast digital information from functional genomics and for a new knowledge environment specifically engineered for the analysis of developmental processes and toxicities. Proof-of-concept tested BDSM using meta-analysis of gene expression data collected from different laboratories, technology platforms, and study models. The composite dataset incorporated 232 microarray comparisons of RNA samples by single or dual microarray platforms, cDNA or oligonucleotide based probes, and human or mouse sequence information. Preliminary results identified system-level features in the embryonic transcriptome as it reacted to various developmental-teratological stimuli. BDSM is open access through the worldwide web (http://systemsanalysis.louisville.edu/) and can be integrated with other bioinformatics tools and resources to advance the pace of discovery in birth defects research.