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