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The flood of high-throughput biological data has led to the expectation that computational (or in silico) models can be used to direct biological discovery, enabling biologists to reconcile heterogeneous data types, find inconsistencies and systematically generate hypotheses. Such a process is fundamentally iterative, where each iteration involves making(More)
Cells operate in dynamic environments using extraordinary communication capabilities that emerge from the interactions of genetic circuitry. The mammalian immune response is a striking example of the coordination of different cell types. Cell-to-cell communication is primarily mediated by signalling molecules that form spatiotemporal concentration(More)
Genome-scale metabolic networks can now be reconstructed based on annotated genomic data augmented with biochemical and physiological information about the organism. Mathematical analysis can be performed to assess the capabilities of these reconstructed networks. The constraints-based framework, with flux balance analysis (FBA), has been used successfully(More)
The large volume of genome-scale data that is being produced and made available in databases on the World Wide Web is demanding the development of integrated mathematical models of cellular processes. The analysis of reconstructed metabolic networks as systems leads to the development of an in silico or computer representation of collections of cellular(More)
Understanding how complex phenotypes arise from individual molecules and their interactions is a primary challenge in biology that computational approaches are poised to tackle. We report a whole-cell computational model of the life cycle of the human pathogen Mycoplasma genitalium that includes all of its molecular components and their interactions. An(More)
MOTIVATION The effort to build a whole-cell model requires the development of new modeling approaches, and in particular, the integration of models for different types of processes, each of which may be best described using different representation. Flux-balance analysis (FBA) has been useful for large-scale analysis of metabolic networks, and methods have(More)
Increasing evidence has shown that population dynamics are qualitatively different from single-cell behaviors. Reporters to probe dynamic, single-cell behaviors are desirable yet relatively scarce. Here, we describe an easy-to-implement and generalizable technology to generate reporters of kinase activity for individual cells. Our technology converts(More)
OBJECTIVE The lesions of Parkinson disease spread through the brain in a characteristic pattern that corresponds to axonal projections. Previous observations suggest that misfolded α-synuclein could behave as a prion, moving from neuron to neuron and causing endogenous α-synuclein to misfold. Here, we characterized and quantified the axonal transport of(More)
A genome-scale metabolic model of Helicobacter pylori 26695 was constructed from genome sequence annotation, biochemical, and physiological data. This represents an in silico model largely derived from genomic information for an organism for which there is substantially less biochemical information available relative to previously modeled organisms such as(More)