Computational Biology and Toxicodynamics.

New approach methodologies (NAMs) refer to any non-animal technology, methodology, approach, or combination thereof that can be used to provide information on chemical hazard and risk assessment that avoids the use of intact animals. A spectrum of models is needed for the integrated analysis of various domains in toxicology to improve predictivity and reduce animal testing. This review focuses on approaches, computer models, and computational intelligence for developmental and reproductive toxicity (predictive DART), providing a means to measure toxicodynamics in simulated systems for quantitative prediction of adverse outcomes phenotypes.

Computational Model of Secondary Palate Fusion and Disruption.

Morphogenetic events are driven by cell-generated physical forces and complex cellular dynamics. To improve our capacity to predict developmental effects from chemical-induced cellular alterations, we built a multicellular agent-based model in CompuCell3D that recapitulates the cellular networks and collective cell behavior underlying growth and fusion of the mammalian secondary palate. The model incorporated multiple signaling pathways (TGFβ, BMP, FGF, EGF, and SHH) in a biological framework to recapitulate morphogenetic events from palatal outgrowth through midline fusion.

Computational modeling and simulation of genital tubercle development.

Hypospadias is a developmental defect of urethral tube closure that has a complex etiology involving genetic and environmental factors, including anti-androgenic and estrogenic disrupting chemicals; however, little is known about the morphoregulatory consequences of androgen/estrogen balance during genital tubercle (GT) development. Computer models that predictively model sexual dimorphism of the GT may provide a useful resource to translate chemical-target bipartite networks and their developmental consequences across the human-relevant chemical universe. Here, we describe a multicellular agent-based model of genital tubercle (GT) development that simulates urethrogenesis from the sexually-indifferent urethral plate stage to urethral tube closure.