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Biosynthetic potentials of metabolites and their hierarchical organization.

Matthäus F, Salazar C, Ebenhöh O - PLoS Comput. Biol. (2008)

Bottom Line: 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.A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials.Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Center for Scientific Computing, University of Heidelberg, Heidelberg, 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 strongly by their biological function. As a general tendency, metabolites which are necessary for essential cellular processes exhibit a larger biosynthetic potential than those involved in secondary metabolism. A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials. Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.

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Hierarchy of compounds based on their biosynthetic potentials.Each box denotes a distinct consensus scope. On the top-left corner of each box, the cluster label and consensus scope size are shown. On the top-right corner, the chemical elements present in most cluster metabolites are given. Further, a representative metabolite of the cluster, whose scope is identical to the cluster's consensus scope, is given. Two consensus scopes are connected by an edge if the lower one is completely contained in the upper one. If the inclusion can be explained by differences in the chemical elements within the cluster members, the missing elements have been noted at the corresponding edge.
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pcbi-1000049-g002: Hierarchy of compounds based on their biosynthetic potentials.Each box denotes a distinct consensus scope. On the top-left corner of each box, the cluster label and consensus scope size are shown. On the top-right corner, the chemical elements present in most cluster metabolites are given. Further, a representative metabolite of the cluster, whose scope is identical to the cluster's consensus scope, is given. Two consensus scopes are connected by an edge if the lower one is completely contained in the upper one. If the inclusion can be explained by differences in the chemical elements within the cluster members, the missing elements have been noted at the corresponding edge.

Mentions: In Figure 2, the hierarchical ordering of the consensus scopes is displayed in a tree form. The boxes contain a cluster representative (a compound with a scope identical to the consensus scope), the cluster label and the consensus scope size, as well as the chemical elements present in most metabolites of the corresponding cluster. In the drawing, clusters with a large biosynthetic potential are positioned above clusters with a lower biosynthetic potential. A line between two clusters is drawn if the consensus scope of the cluster positioned below is a subset of the consensus scope of the cluster positioned above. For clarity, indirect inclusions are not depicted (although the scope of glucose is naturally contained in that of APS, a line has not been drawn). Also partial overlaps of consensus scopes are not depicted. Because the consensus scopes of clusters VII and XI are disjoint from all others, they are represented by isolated nodes.


Biosynthetic potentials of metabolites and their hierarchical organization.

Matthäus F, Salazar C, Ebenhöh O - PLoS Comput. Biol. (2008)

Hierarchy of compounds based on their biosynthetic potentials.Each box denotes a distinct consensus scope. On the top-left corner of each box, the cluster label and consensus scope size are shown. On the top-right corner, the chemical elements present in most cluster metabolites are given. Further, a representative metabolite of the cluster, whose scope is identical to the cluster's consensus scope, is given. Two consensus scopes are connected by an edge if the lower one is completely contained in the upper one. If the inclusion can be explained by differences in the chemical elements within the cluster members, the missing elements have been noted at the corresponding edge.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2289774&req=5

pcbi-1000049-g002: Hierarchy of compounds based on their biosynthetic potentials.Each box denotes a distinct consensus scope. On the top-left corner of each box, the cluster label and consensus scope size are shown. On the top-right corner, the chemical elements present in most cluster metabolites are given. Further, a representative metabolite of the cluster, whose scope is identical to the cluster's consensus scope, is given. Two consensus scopes are connected by an edge if the lower one is completely contained in the upper one. If the inclusion can be explained by differences in the chemical elements within the cluster members, the missing elements have been noted at the corresponding edge.
Mentions: In Figure 2, the hierarchical ordering of the consensus scopes is displayed in a tree form. The boxes contain a cluster representative (a compound with a scope identical to the consensus scope), the cluster label and the consensus scope size, as well as the chemical elements present in most metabolites of the corresponding cluster. In the drawing, clusters with a large biosynthetic potential are positioned above clusters with a lower biosynthetic potential. A line between two clusters is drawn if the consensus scope of the cluster positioned below is a subset of the consensus scope of the cluster positioned above. For clarity, indirect inclusions are not depicted (although the scope of glucose is naturally contained in that of APS, a line has not been drawn). Also partial overlaps of consensus scopes are not depicted. Because the consensus scopes of clusters VII and XI are disjoint from all others, they are represented by isolated nodes.

Bottom Line: 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.A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials.Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Center for Scientific Computing, University of Heidelberg, Heidelberg, 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 strongly by their biological function. As a general tendency, metabolites which are necessary for essential cellular processes exhibit a larger biosynthetic potential than those involved in secondary metabolism. A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials. Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.

Show MeSH