Integrating transcriptional activity in genome-scale models of metabolism

Baños, Daniel Trejo; Trébulle, Pauline; Elati, Mohamed

doi:10.1186/s12918-017-0507-0

Cited by 21 publications

(19 citation statements)

References 36 publications

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“…Here, the function takes as argument two valid models for the "sybil" R package and a customizable threshold value to filter functions to be reported. In this aspect, we chose an arbitrary threshold value greater or equal to 2-fold times for reactions with an absolute change between the unconstrained and constrained metabolic scenarios, as reported in previous models (Hausen et al, 2015;Banos et al, 2017).…”

Section: Identifying Flux Changes Between Scenariosmentioning

confidence: 99%

Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach

et al. 2020

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Inflammation is a complex biological response to injuries, metabolic disorders or infections. In the brain, astrocytes play an important role in the inflammatory processes during neurodegenerative diseases. Recent studies have shown that the increase of free saturated fatty acids such as palmitic acid produces a metabolic inflammatory response in astrocytes generally associated with damaging mechanisms such as oxidative stress, endoplasmic reticulum stress, and autophagic defects. In this aspect, the synthetic neurosteroid tibolone has shown to exert protective functions against inflammation in neuronal experimental models without the tumorigenic effects exerted by sexual hormones such as estradiol and progesterone. However, there is little information regarding the specific mechanisms of tibolone in astrocytes during inflammatory insults. In the present study, we performed a genome-scale metabolic reconstruction of astrocytes that was used to study astrocytic response during an inflammatory insult by palmitate through Flux Balance Analysis methods and data mining. In this aspect, we assessed the metabolic fluxes of human astrocytes under three different scenarios: healthy (normal conditions), induced inflammation by palmitate, and tibolone treatment under palmitate inflammation. Our results suggest that tibolone reduces the L-glutamate-mediated neurotoxicity in astrocytes through the modulation of several metabolic pathways involved in glutamate uptake. We also identified a set of reactions associated with the protective effects of tibolone, including the upregulation of taurine metabolism, gluconeogenesis, cPPAR and the modulation of calcium signaling pathways. In conclusion, the different scenarios studied in our model allowed us to identify several metabolic fluxes perturbed under an inflammatory response and the protective mechanisms exerted by tibolone.

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Section: Identifying Flux Changes Between Scenariosmentioning

confidence: 99%

Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach

et al. 2020

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“…Modeling of the yeast diauxic shift is especially challenging because of the complexity of the biology involved, and the need to include subsystems operating at different time scales, and serving different purposes (5). The modeling requires integration of (1) a model of control of metabolism (cell signaling), and (2) a genome scale model of metabolism (1).…”

Section: Resultsmentioning

confidence: 99%

Closed-loop cycles of experiment design, execution, and learning accelerate systems biology model development in yeast

Coutant

Roper

Baños

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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One of the most challenging tasks in modern science is the development of systems biology models: Existing models are often very complex but generally have low predictive performance. The construction of high-fidelity models will require hundreds/thousands of cycles of model improvement, yet few current systems biology research studies complete even a single cycle. We combined multiple software tools with integrated laboratory robotics to execute three cycles of model improvement of the prototypical eukaryotic cellular transformation, the yeast (Saccharomyces cerevisiae) diauxic shift. In the first cycle, a model outperforming the best previous diauxic shift model was developed using bioinformatic and systems biology tools. In the second cycle, the model was further improved using automatically planned experiments. In the third cycle, hypothesis-led experiments improved the model to a greater extent than achieved using high-throughput experiments. All of the experiments were formalized and communicated to a cloud laboratory automation system (Eve) for automatic execution, and the results stored on the semantic web for reuse. The final model adds a substantial amount of knowledge about the yeast diauxic shift: 92 genes (+45%), and 1,048 interactions (+147%). This knowledge is also relevant to understanding cancer, the immune system, and aging. We conclude that systems biology software tools can be combined and integrated with laboratory robots in closed-loop cycles.

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“…Additionally, rFBA [31], SR-FBA [32], PROM [28] and tFBA [29] were already classified and categorized according to the deviations from traditional phenotype simulation with FBA [23]. Besides of these previous reports, TIGER toolbox [33], GIM 3 E [34], FlexFlux [35], TRFBA [36], CoRegFlux [37] and ME-models [38] were never surveyed before.…”

Section: Methods For Integrating Trn Reconstruction or Gene Expressiomentioning

confidence: 99%

Towards the Reconstruction of Integrated Genome-Scale Models of Metabolism and Gene Expression

Cruz

Lima

Faria

et al. 2019

Practical Applications of Computational Biology and Bioinformatics, 13th International Conference

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The reconstruction of integrated genome-scale models of metabolism and gene expression has been a challenge for a while now. In fact, various methods that allow integrating reconstructions of Transcriptional Regulatory Networks, gene expression data or both into Genome-Scale Metabolic Models have been proposed. Several of these methods are surveyed in this article, which allowed identifying their strengths and weaknesses concerning the reconstruction of integrated models for multiple prokaryotic organisms. Additionally, the main resources of regulatory information were also surveyed, as the existence of novel sources of regulatory information and gene expression data may contribute for the improvement of methodologies referred herein.

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Integrating transcriptional activity in genome-scale models of metabolism

Cited by 21 publications

References 36 publications

Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach

Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach

Closed-loop cycles of experiment design, execution, and learning accelerate systems biology model development in yeast

Towards the Reconstruction of Integrated Genome-Scale Models of Metabolism and Gene Expression

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