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Fast reconstruction of compact context-specific metabolic networks via integration of microarray data

Recently we proposed an algorithm for the fast reconstruction of compact context-specific metabolic networks (FASTCORE) that allowed dropping the reconstruction time to the time order of seconds (Vlassis et al.,2014). This extremely low computational demand opens new possibilities for improving the quality of the models. Several rounds of model reconstruction, testing of the model's predictions against real experimental data, curation steps of the input model and the set of core reactions as well as cross-validations assays are required to reconstruct high-quality models. These semi-automated model curations steps are in such extend not possible with competing algorithms due to their high computational demands. To adapt FASTCORE for the integration of microarray data, we therefore propose a new workflow: FASTCORMICS. FASTCORMICS requires as input microarray data and a Genome-scale reconstruction. FASTCORMICS is devoid of heuristic parameter settings and has a low computational demand with overall building times in the order of a few minutes. FASTCORMICS preprocesses the microarrays data with the discretization tool Barcode (Zillox et al, 2007). Barcode uses prior knowledge on the intensity distribution of each probe set for a given microarray platform to segregate between expressed genes and non-expressed genes. This preprocessing step allows circumventing the need of setting a heuristic expression threshold, which is critical for the output models as in response to this threshold alternative pathways or subsystems might be included or excluded, thereby heavily changing the functionalities of the model. In general, FASTCORMICS outperforms competing algorithms and allows obtaining high-quality, robust models in a high-throughput manner. This will allow the use of metabolic modelling as routine process for the analysis of microarray data e.g. in the field of personalized medicine.