The archetypal bacterium model generator is a tool for generating WC models that represent user-specified numbers of genes, RNA, proteins, and reactions. The models generated by the model generator represent the metabolism, replication, transcription, translation, RNA and protein degradation, and cell division of a typical bacterium. The archetypal bacterium model generator is particularly useful for driving the development of WC modeling tools, as well as teaching WC modeling.
The M. genitalium WC model was the first model that represented each characterized gene function of an organism. The model is composed of 28 submodels of 28 cellular processes. In total, the model represents the functions of 401 genes, 722 compounds, 1,857 reactions, and 1,836 parameters. In addition to demonstrating the feasibility of WC models, the model has been used to gain new insights into cell cycle regulation, learn unknown parameters, and suggest new uses of existing antibiotics for Mycoplasmas.
Author: Covert Lab, Stanford
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Reference: Karr JR et al. Cell 2012.
The M. pneumoniae WC model will be the most comprehensive, most systematically constructed, and most extensible WC model to date. The model will represent all of the major cellular functions of M. pneumoniae, including the function each characterized gene. The model will be based primarily on M. pneumoniae genomic data. The model will be used to drive the development of WC modeling methods, as well as to help design a reliable, energy efficient, fast-growing chassis for future bioengineering.
Homo sapiens (H1-hESC)
The H1 human embryonic stem cell (hESC) model is the first step toward WC models of human cells. The model will represent the core cellular functions of all human cells including their metabolism, DNA replication, transcription, translation, protein complexation, RNA and protein degradation, and division. The model focuses on H1-hESCs because ESCs behave as individual cells, because ESC lines are karyotypically normal, because ESCs grow quickly, and because H1-hESC has been extensively characterized. In addition to demonstrating the feasibility of human WC models and driving the development of WC modeling tools, the model will be used to gain insights into how stem cells maintain pluripotency.
Homo sapiens cancer signaling (MCF10A)
A mechanistic ordinary differential equation model describing the interactions between commonly mutated pan-cancer signaling pathways—receptor tyrosine kinases, Ras/RAF/ERK, PI3K/AKT, mTOR, cell cycle, DNA damage, and apoptosis.
Availability: Bouhaddou M et al. A mechanistic pan-cancer pathway model informed by multi-omics data interprets stochastic cell fate responses to drugs and mitogens. PLoS Comput Biol 26, e1005985 (2018).