B06

B06

Reciprocal transfer of knowledge from population-based genetic screens to whole-body, organ-resolved models of human metabolism

Project summary

We hypothesize that combining knowledge-driven constraint-based whole-body modeling with hypothesis-generating research on the genetics of human metabolism will facilitate novel mechanistic insights, overcoming the limitations of each paradigm alone in small data situations. We will transfer information from genetic association analyses into in silico models of human metabolism, and vice versa. Specifically, we will utilize whole-body models based on the constraint-based modeling approach as an independent validation resource for metabolite-gene associations. The associations will be obtained from gene-based tests of rare, deleterious variants and their effect on metabolite levels in plasma and urine. Novel knowledge about human physiology and metabolism originating from these association studies will be fed back and continuously improve the whole-body models.

Our methods

  • Combining knowledge- and data-driven modeling
  • Differential equations

Principal investigator 1

Doctoral researcher position 1

(supervised by PI Hertel; located in Greifswald)

Tasks

Perform in silico experiments employing various modeling strategies in the field of constraint-based modeling and reconstruction analysis. This includes the integration of statistical approaches to analyze populations of models generated via personalized whole body modelling.

Requirements

  • Master’s degree in computational biology, applied mathematics, biotechnology, bioinformatics, or life sciences with quantitative focus
  • Good understanding of standard statstical analysis approaches to omics data such as regression analysis and multivariate methodologies
  • Programming knowledge in Matlab, R, Python, or similar
  • Ideally, experience in constraint-based modeling using the COBRA toolbox, with differential equation modeling of metabolic pathways, and working in HPC environments
  • Interest in metabolism and biochemistry

Principal investigator 2

 

 

 

Administrative Manager

Marc Schumacher

Institute of Medical Biometry and Statistics,
Faculty of Medicine and Medical Center –
University of Freiburg