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Hierarchical Modularity in Hierarchical Modularity in Metabolic Networks Metabolic Networks Erzsébet Ravasz Erzsébet Ravasz Center for Nonlinear Studies, Los Alamos National Laboratory Center for Nonlinear Studies, Los Alamos National Laboratory
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Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Jun 18, 2021

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Page 1: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Hierarchical Modularity inHierarchical Modularity in

Metabolic NetworksMetabolic Networks

Erzsébet RavaszErzsébet Ravasz

Center for Nonlinear Studies, Los Alamos National LaboratoryCenter for Nonlinear Studies, Los Alamos National Laboratory

Page 2: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Networks?

Many different components A variety of interactions

The cell is not regular

Systems Biology Data on system level Methods and focus shift Asking for statistical physics

Not a lattice!

System as a whole:network!

Page 3: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Networks in life

Genetic regulation Protein-protein interactions Food webs Neuron networks

Biology

Page 4: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Networks in life

Metabolic pathways

Page 5: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Networks in life

Do these networks haveanything in common

???

Page 6: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Degree distribution

Not random networks!

Proteininteractions

Metabolic networks

Food webs

Page 7: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Clustering

Clustering coefficient

Modular organization protein complexes regulatory modules pathways

High average in real networks Scale-free model: C ~ (ln N) 2/N

Page 8: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Module hierarchy

Hierarchical model

Modular And Scale-free?

Page 9: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Hierarchy in Biology

Protein-protein interaction Regulatory networks

Metabolic networks

Page 10: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

The metabolism of E. Coli

Biochemical reduction

Topological reduction

Page 11: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Finding the modules

Hierarchical clustering

Similarity matrix

Average linkage clustering(UPGMA)

Page 12: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

Module lethality

Pyrimidine metabolism Genome-wide lethalitymeasurement

Page 13: Hierarchical Modularity in Metabolic Networks•Albert László Barabási •Zoltán Oltvai. A-LYASE CITRATE MALONATE. OXALO- ACETATE SUCCINATE GLYCYL- tRNA ACETYL-C0A CoA-S S.AMINOLEVULINATE

http://www.nd.edu/~networks

Thank you!

Thanks to:•Albert László Barabási•Zoltán Oltvai