3 research outputs found
On the effects of alternative optima in context-specific metabolic model predictions
Recent methodological developments have facilitated the integration of
high-throughput data into genome-scale models to obtain context-specific
metabolic reconstructions. A unique solution to this data integration problem
often may not be guaranteed, leading to a multitude of context-specific
predictions equally concordant with the integrated data. Yet, little attention
has been paid to the alternative optima resulting from the integration of
context-specific data. Here we present computational approaches to analyze
alternative optima for different context-specific data integration instances.
By using these approaches on metabolic reconstructions for the leaf of
Arabidopsis thaliana and the human liver, we show that the analysis of
alternative optima is key to adequately evaluating the specificity of the
predictions in particular cellular contexts. While we provide several ways to
reduce the ambiguity in the context-specific predictions, our findings indicate
that the existence of alternative optimal solutions warrant caution in detailed
context-specific analyses of metabolism
Mechanistic insights into bacterial metabolic reprogramming from omics-integrated genome-scale models.
Understanding the adaptive responses of individual bacterial strains is crucial for microbiome engineering approaches that introduce new functionalities into complex microbiomes, such as xenobiotic compound metabolism for soil bioremediation. Adaptation requires metabolic reprogramming of the cell, which can be captured by multi-omics, but this data remains formidably challenging to interpret and predict. Here we present a new approach that combines genome-scale metabolic modeling with transcriptomics and exometabolomics, both of which are common tools for studying dynamic population behavior. As a realistic demonstration, we developed a genome-scale model of Pseudomonas veronii 1YdBTEX2, a candidate bioaugmentation agent for accelerated metabolism of mono-aromatic compounds in soil microbiomes, while simultaneously collecting experimental data of P. veronii metabolism during growth phase transitions. Predictions of the P. veronii growth rates and specific metabolic processes from the integrated model closely matched experimental observations. We conclude that integrative and network-based analysis can help build predictive models that accurately capture bacterial adaptation responses. Further development and testing of such models may considerably improve the successful establishment of bacterial inoculants in more complex systems