biosynthetic potentials of metabolites and their hierarchical organization生物合成代谢物及其层次组织的潜力.pdf

Biosynthetic Potentials of Metabolites and Their Hierarchical Organization ¨ 1. 2. ¨ 3,4. Franziska Matthaus , Carlos Salazar , Oliver Ebenhoh * 1 Interdisciplinary Center for Scientific Computing, University of Heidelberg, Heidelberg, Germany, 2 German Cancer Research Center, Heidelberg, Germany, 3 Max-Planck- Institute for Molecular Plant Physiology, Potsdam-Golm, Germany, 4 Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany Abstract A major challenge in systems biology is to understand how complex and highly connected metabolic networks are organized. The structure of these networks is investigated here by identifying sets of metabolites that have a similar biosynthetic potential. We measure the biosynthetic potential of a particular compound by determining all metabolites than can be produced from it and, following a terminology introduced previously, call this set the scope of the compound. To identify groups of compounds with similar scopes, we apply a hierarchical clustering method. We find that compounds within the same cluster often display similar chemical structures and appear in the same metabolic pathway. For each cluster we define a consensus scope by determining a set of metabolites that is most similar to all scopes within the cluster. This allows for a generalization from scopes of single compounds to scopes of a chemical family. We observe that most of the resulting consensus scopes overlap or are fully contained in others, revealing a hierarchical ordering of metabolites according to their biosynthetic potential. Our investigations show that this hierarchy is not only determined by the chemical complexity of the metabolites, but also stro