P3‐074: Transcriptome‐To‐Reactome Biosimulation: Oxidative Pathways to Apoptotic Cell Death

Oxidative stress and apoptosis are recognized to play major roles in the pathogenesis of Alzheimer's disease (AD). The objective of this study was to assess, in silico, a set of oxidative stress measures reported on frontal cortex homogenates, ex vivo (Ansari and Scheff, 2010) and associated indices of apoptosis. We simulated the CA1 by linking genome-wide transcription profiles from age matched controls and incipient, moderate and severe cases of AD (from NCBI GEO GSE1297) with corresponding reactions in a biosimulation model, i.e., to derive parameters for a deterministic kinetic model, Transcriptome-To-Reactome™ Biosimulation: Oxidative Pathways to Apoptotic Cell Death. The apoptosis pathway from Reactome® and the one carbon glutathione pathways (Reed et al., 2008) were used to simulate oxidative stress and cell death, using COPASI®. This model has 13 compartments, 442 species, 260 reactions and 326 parameters derived from expression levels for 380 genes. Time-series simulations were run using ordinary differential equations to generate level values for reactants and flux values for reactions.