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Aite, M., Chevallier, M., Frioux, C., Trottier, C., Got, J., Cortes, M. P., et al. (2018). Traceability, reproducibility and wiki-exploration for “a-la-carte” reconstructions of genome-scale metabolic models. PLoS Comput. Biol., 14(5), 25 pp.
Abstract: Genome-scale metabolic models have become the tool of choice for the global analysis of microorganism metabolism, and their reconstruction has attained high standards of quality and reliability. Improvements in this area have been accompanied by the development of some major platforms and databases, and an explosion of individual bioinformatics methods. Consequently, many recent model s result from “a la carte” pipelines, combining the use of platforms, individual tools and biological expertise to enhance the quality of the reconstruction. Although very useful, introducing heterogeneous tools, that hardly interact with each other, causes loss of traceability and reproducibility in the reconstruction process. This represents a real obstacle, especially when considering less studied species whose metabolic reconstruction can greatly benefit from the comparison to good quality models of related organisms. This work proposes an adaptable workspace, AuReMe, for sustainable reconstructions or improvements of genome-scale metabolic models involving personalized pipelines. At each step, relevant information related to the modifications brought to the model by a method is stored. This ensures that the process is reproducible and documented regardless of the combination of tools used. Additionally, the workspace establishes a way to browse metabolic models and their metadata through the automatic generation of ad-hoc local wikis dedicated to monitoring and facilitating the process of reconstruction. AuReMe supports exploration and semantic query based on RDF databases. We illustrate how this workspace allowed handling, in an integrated way, the metabolic reconstructions of non-model organisms such as an extremophile bacterium or eukaryote algae. Among relevant applications, the latter reconstruction led to putative evolutionary insights of a metabolic pathway.
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Travisany, D., Goles, E., Latorre, M., Cort?s, M. P., & Maass, A. (2020). Generation and robustness of Boolean networks to model Clostridium difficile infection. Nat. Comput., 19(1), 111–134.
Abstract: One of the more common healthcare associated infection is Chronic diarrhea. This disease is caused by the bacterium Clostridium difficile which alters the normal composition of the human gut flora. The most successful therapy against this infection is the fecal microbial transplant (FMT). They displace C. difficile and contribute to gut microbiome resilience, stability and prevent further episodes of diarrhea. The microorganisms in the FMT their interactions and inner dynamics reshape the gut microbiome to a healthy state. Even though microbial interactions play a key role in the development of the disease, currently, little is known about their dynamics and properties. In this context, a Boolean network model for C. difficile infection (CDI) describing one set of possible interactions was recently presented. To further explore the space of possible microbial interactions, we propose the construction of a neutral space conformed by a set of models that differ in their interactions, but share the final community states of the gut microbiome under antibiotic perturbation and CDI. To begin with the analysis, we use the previously described Boolean network model and we demonstrate that this model is in fact a threshold Boolean network (TBN). Once the TBN model is set, we generate and use an evolutionary algorithm to explore to identify alternative TBNs. We organize the resulting TBNs into clusters that share similar dynamic behaviors. For each cluster, the associated neutral graph is constructed and the most relevant interactions are identified. Finally, we discuss how these interactions can either affect or prevent CDI.
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