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Computational Modeling of Human Metabolism and Its Application to Systems Biomedicine

  • Maike K. Aurich
  • Ines ThieleEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1386)

Abstract

Modern high-throughput techniques offer immense opportunities to investigate whole-systems behavior, such as those underlying human diseases. However, the complexity of the data presents challenges in interpretation, and new avenues are needed to address the complexity of both diseases and data. Constraint-based modeling is one formalism applied in systems biology. It relies on a genome-scale reconstruction that captures extensive biochemical knowledge regarding an organism. The human genome-scale metabolic reconstruction is increasingly used to understand normal cellular and disease states because metabolism is an important factor in many human diseases. The application of human genome-scale reconstruction ranges from mere querying of the model as a knowledge base to studies that take advantage of the model’s topology and, most notably, to functional predictions based on cell- and condition-specific metabolic models built based on omics data.

An increasing number and diversity of biomedical questions are being addressed using constraint-based modeling and metabolic models. One of the most successful biomedical applications to date is cancer metabolism, but constraint-based modeling also holds great potential for inborn errors of metabolism or obesity. In addition, it offers great prospects for individualized approaches to diagnostics and the design of disease prevention and intervention strategies. Metabolic models support this endeavor by providing easy access to complex high-throughput datasets. Personalized metabolic models have been introduced. Finally, constraint-based modeling can be used to model whole-body metabolism, which will enable the elucidation of metabolic interactions between organs and disturbances of these interactions as either causes or consequence of metabolic diseases. This chapter introduces constraint-based modeling and describes some of its contributions to systems biomedicine.

Key words

Systems biology Constraint-based modeling Personalized health Metabolomics OMICS COBRA Flux balance analysis Cancer metabolism Human disease Personalized models 

Notes

Acknowledgment

This study was supported by an ATTRACT program grant (FNR/A12/01) from the Luxembourg National Research Fund (FNR).

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© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Luxembourg Center for Systems BiomedicineUniversity of LuxembourgEsch-sur-alzetteLuxembourg

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