Stage Master

Constraint-Based Reconstruction and Analysis (COBRA) is a widely used computational modeling approach that relies on genome-scale reconstructions of metabolism to predict metabolic fluxes on the level of the whole cell. Genome-scale models have been successfully applied to the contextualization of meta-omics data such as transcriptomics, proteomics, and metabolomics. Through integration of these meta-omics data, genome-scale models can give rise to personalized models that can predict potential biomarkers of multifactorial diseases or predict personalized dietary or therapeutic interventions. In this project, Constraint-Based Reconstruction and Analysis (COBRA) will be applied to contextualize meta-omics data from bariatric surgery patients. The proposed MSc thesis project will take six months and take place at Campus Brabois, Nancy, France.
ALDEPI / OBESEPI is a cohort of patients with morbid obesity and undergoing Bariatric surgery (https://clinicaltrials.gov/ct2/show/NCT02663388). Available data for the participants include transcriptome and proteome from liver and adipose tissue, methylome from liver, adipose tissue, and blood, one-carbon metabolite measurements, clinical parameters (e.g., insulin), and DEXA (dual energy X-Ray absorptiometry) measurements for up to 400 patients.
Here, the metabolism of bariatric surgery patients will be modeled on a tissue-specific level. Transcriptomic and proteomic data from obese patients before and after bariatric surgery will be integrated into tissue-specific genome-scale models of human liver and adipose tissue, resulting in patient-specific models. These personalized models will then be integrated and interrogated in simulations to elucidate liver and adipocyte metabolism in patients.
The generated individual-specific fluxes will be correlated with methylome measurements from liver, adipose tissue, and blood, as well as with clinical parameters including DEXA measurements. These analyses will yield insight into epigenetic regulation of enzymes with different activity after bariatric surgery. Fluxes correlated with positive outcomes of bariatric surgery as indicated by clinical parameters could also be identified.