(3en) Advancing Genome Scale Models

The development of genome scale models (GSM) for a variety of microbial, eykaryotic and multi-cellelar organisms is proceeding with an accelerating pace. Automated reconstruction tools such as ModelSEED, Pathway Tools, and others are increasingly being utilized to quickly arrive at draft compilations of metabolic models followed by detailed curation to improve upon modeling components crucial for answering the queries relevant to the specific organism and study. Typically, simulations are carried out for an idealized growth substrate typically containing a single carbon substrate (e.g., glucose). Regulation is customarily handled by shutting off specific reactions in the presence of a specific nutrient environment. For example, in the iAF1260 E. colimodel, there are specific reaction restrictions for anaerobic, aerobic, and aerobic with glucose growth conditions. In this poster, a second generation model for Costridium acetobutylicum is presented.

We make extensive use of MetRxn (http://metrxn.che.psu.edu), a web-based knowledgebase that includes standardized metabolite and reaction descriptions and integrates information from 8 databases and 44 metabolic models into a single unified data set. In addition to metabolic biotransformations, we describe the inclusion of regulatory information. The establishment of detailed gene-protein-reaction associations enables us to properly localize regulatory interactions at the transcriptional, protein or metabolite level and rely on the gene-protein-reaction (GPR) connections to propagate their action through metabolism. We make use of gene and protein expression data and a variety of growth conditions.