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Genome-scale metabolic models (GEMs) are extensively used to simulate cell metabolism and predict cell phenotypes. GEMs can also be tailored to generate context-specific GEMs, using omics data integration approaches. To date, many integration approaches have been developed, however, each with specific pros and cons; and none of these algorithms systematically outperforms the others. The key to successful implementation of such integration algorithms lies in the optimal selection of parameters, and thresholding is a crucial component in this process. To improve the predictive accuracy of context-specific models, we introduce a new integration framework that improves the ranking of related genes and homogenizes the expression values of those gene sets using single-sample Gene Set Enrichment Analysis (ssGSEA). In this study, we coupled ssGSEA with GIMME and validated the advantages of the proposed framework to predict the ethanol formation of yeast grown in the glucose-limited chemostats, and to simulate metabolic behaviors of yeast growth in four different carbon sources. This framework enhances the predictive accuracy of GIMME which we demonstrate for predicting the yeast physiology in nutrient-limited cultures. [ABSTRACT FROM AUTHOR]

The evolution of biochemical models is difficult to track. At present, it is not possible to inspect the differences between model versions at the network level. Biochemical models are often constructed in a distributed, non-linear process: collaborators create model versions on different branches from novel information, model extensions, during curation and adaption. To discuss and align the versions, it is helpful to abstract the changes to the network level. The differences between two model versions can be detected by the software tool BiVeS. However, it cannot show the structural changes resulting from the differences. Here, we present a method to visualise the differences between model versions effectively. We developed a JSON schema to communicate the differences at the network level and extended BiVeS accordingly. Additionally, we developed DiVil, a web-based tool to represent the model and the differences as a standardised network using D3. It combines an automatic layout with an interactive user interface to improve the visualisation and to inspect the model. The network can be exported in standardised formats as images or markup language. Our method communicates the structural differences between model versions. It facilitates the discussion of changes and thus supports the collaborative and non-linear nature of model development. Availability and implementation: DiVil prototype: https://divil.bio.informatik.uni-rostock.de, Code on GitHub: https://github.com/Gebbi8/DiVil, licensed under Apache License 2.0. Contact: url="tom.gebhardt@uni-rostock.de. [ABSTRACT FROM AUTHOR]