#TERA AVG FALSE POSITIVE DRIVERS#

The Toxicity Reference Database (ToxRefDB) is the U.S. A number of cleft palate teratogens have been identified from in vivo mammalian studies published in both the biomedical literature and in regulatory guideline prenatal developmental toxicity studies that routinely evaluate secondary palate formation ( Collins, 2006). The genetic factors are identified through human studies and animal models and have indicated potential gene pathways involved in cleft palate ( Wattanawong, Rattanasiri, McEvoy, Attia, & Thakkinstian, 2016). Animal models and human epidemiological studies have revealed complex etiology for this malformation, with genetic factors, environmental factors, and their interactions underlying the risk.

#TERA AVG FALSE POSITIVE DRIVERS#

This general data-driven approach offers a promising avenue for mining chemical-bioassay drivers of complex developmental endpoints where data are often limited.Д¬left lip and/or palate is a common birth defect occurring in 1 out of 700 live births worldwide ( Dixon, Marazita, Beaty, & Murray, 2011), costing over $15 million annually in direct hospital expenses in the United States ( Russo & Elixhauser, 2007). These patterns and linkages were organized into preliminary decision trees and the resulting inferences were mapped to a putative adverse outcome pathway (AOP) framework for cleft palate supported by literature evidence of current mechanistic understanding. The clusters corresponded to ToxCast assays for cytochrome P450s, G protein-coupled receptors, retinoic acid receptors, the glucocorticoid receptor, and tyrosine kinases/phosphatases. Patterns of enrichment were confirmed on the complete dataset, i.e., including cleft palate inactives, and putative molecular initiating events identified. Following unsuccessful attempts to derive a global prediction model using structural and gene score descriptors, hierarchical clustering was applied to the set of 63 cleft palate positives to extract local structure-bioactivity clusters for follow-up study. ToxCast assay results were filtered for cytotoxicity and grouped by target gene activity to produce a вЂgene scoreвЂ™. To characterize the potential molecular targets for chemical-induced cleft palate, we mined the ToxCast high-throughput screening database for patterns and linkages in bioactivity profiles and chemical structural descriptors. A dataset of 500 chemicals evaluated for their ability to induce cleft palate in animal prenatal developmental studies was compiled from ToxRefDB and the biomedical literature, which included 63 cleft palate active and 437 inactive chemicals. As a developmental outcome, it presents a challenging, mechanistically complex endpoint for predictive modeling.

Cleft palate has been linked to both genetic and environmental factors that perturb key events during palatal morphogenesis.

Tera avg false positive