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Network modularity, currency metabolites representa- tions of and - - PowerPoint PPT Presentation

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Network modularity, currency metabolites and graph Network modularity, currency metabolites representa- tions of and graph representations of metabolism metabolism PETTER HOLME metabolic Petter Holme networks, intro networks KTH,

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SLIDE 1

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

Network modularity, currency metabolites and graph representations of metabolism

Petter Holme

KTH, CSC, Computational Biology

April 2, 2008, Physics of distributed information systems

http://www.csc.kth.se/∼pholme/

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SLIDE 2

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

why?

Metabolism = is the set of all chemical reactions in an

  • rganism? Why study it by networks?

Details (reaction coeficient, subcellular localisation, etc.) are not known. So to study large-scale structures, a detailed picture makes little sense. There are many methods to analyze graphs statistically.

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SLIDE 3

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

why?

Metabolism = is the set of all chemical reactions in an

  • rganism? Why study it by networks?

Details (reaction coeficient, subcellular localisation, etc.) are not known. So to study large-scale structures, a detailed picture makes little sense. There are many methods to analyze graphs statistically.

slide-4
SLIDE 4

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

why?

Metabolism = is the set of all chemical reactions in an

  • rganism? Why study it by networks?

Details (reaction coeficient, subcellular localisation, etc.) are not known. So to study large-scale structures, a detailed picture makes little sense. There are many methods to analyze graphs statistically.

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SLIDE 5

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

complex network studies

. . . of biochemical networks. What questions can we ask? how can the large-scale organization be characterized? are there any universal features over different species? do the differences tell us something about evolution? can we identify functional modules? . . the functions of molecules?

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SLIDE 6

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

complex network studies

. . . of biochemical networks. What questions can we ask? how can the large-scale organization be characterized? are there any universal features over different species? do the differences tell us something about evolution? can we identify functional modules? . . the functions of molecules?

slide-7
SLIDE 7

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

complex network studies

. . . of biochemical networks. What questions can we ask? how can the large-scale organization be characterized? are there any universal features over different species? do the differences tell us something about evolution? can we identify functional modules? . . the functions of molecules?

slide-8
SLIDE 8

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

complex network studies

. . . of biochemical networks. What questions can we ask? how can the large-scale organization be characterized? are there any universal features over different species? do the differences tell us something about evolution? can we identify functional modules? . . the functions of molecules?

slide-9
SLIDE 9

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

complex network studies

. . . of biochemical networks. What questions can we ask? how can the large-scale organization be characterized? are there any universal features over different species? do the differences tell us something about evolution? can we identify functional modules? . . the functions of molecules?

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SLIDE 10

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

complex network studies

. . . of biochemical networks. What questions can we ask? how can the large-scale organization be characterized? are there any universal features over different species? do the differences tell us something about evolution? can we identify functional modules? . . the functions of molecules?

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

wallpapers

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

  • B. burgdorferi, 2000
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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

human, 2006

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what systems?

What systems can be analyzed with complex network methods? items are, naturally, coupled pairwise MAYBE? the network is relatively sparse (the average degree is constant) ALMOST TRUE there is a dynamic system on the network TRUE! the time scale of this dynamics is faster than the dynamics of network evolution TRUE!

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SLIDE 15

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what systems?

What systems can be analyzed with complex network methods? items are, naturally, coupled pairwise MAYBE? the network is relatively sparse (the average degree is constant) ALMOST TRUE there is a dynamic system on the network TRUE! the time scale of this dynamics is faster than the dynamics of network evolution TRUE!

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SLIDE 16

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what systems?

What systems can be analyzed with complex network methods? items are, naturally, coupled pairwise MAYBE? the network is relatively sparse (the average degree is constant) ALMOST TRUE there is a dynamic system on the network TRUE! the time scale of this dynamics is faster than the dynamics of network evolution TRUE!

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SLIDE 17

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what systems?

What systems can be analyzed with complex network methods? items are, naturally, coupled pairwise MAYBE? the network is relatively sparse (the average degree is constant) ALMOST TRUE there is a dynamic system on the network TRUE! the time scale of this dynamics is faster than the dynamics of network evolution TRUE!

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SLIDE 18

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what systems?

What systems can be analyzed with complex network methods? items are, naturally, coupled pairwise MAYBE? the network is relatively sparse (the average degree is constant) ALMOST TRUE there is a dynamic system on the network TRUE! the time scale of this dynamics is faster than the dynamics of network evolution TRUE!

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SLIDE 19

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what systems?

What systems can be analyzed with complex network methods? items are, naturally, coupled pairwise MAYBE? the network is relatively sparse (the average degree is constant) ALMOST TRUE there is a dynamic system on the network TRUE! the time scale of this dynamics is faster than the dynamics of network evolution TRUE!

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SLIDE 20

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what systems?

What systems can be analyzed with complex network methods? items are, naturally, coupled pairwise MAYBE? the network is relatively sparse (the average degree is constant) ALMOST TRUE there is a dynamic system on the network TRUE! the time scale of this dynamics is faster than the dynamics of network evolution TRUE!

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SLIDE 21

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what systems?

What systems can be analyzed with complex network methods? items are, naturally, coupled pairwise MAYBE? the network is relatively sparse (the average degree is constant) ALMOST TRUE there is a dynamic system on the network TRUE! the time scale of this dynamics is faster than the dynamics of network evolution TRUE!

slide-22
SLIDE 22

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what systems?

What systems can be analyzed with complex network methods? items are, naturally, coupled pairwise MAYBE? the network is relatively sparse (the average degree is constant) ALMOST TRUE there is a dynamic system on the network TRUE! the time scale of this dynamics is faster than the dynamics of network evolution TRUE!

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

representations

ATP + NADH ↔ ADP + NADPH NADH kinase

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

representations

ATP + NADH ↔ ADP + NADPH vertices: substrates edges: between products / substrates

  • n different sides
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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

representations

ATP + NADH ↔ ADP + NADPH vertices: substrates edges: between products / substrates

  • n the same side
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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

representations

ATP + NADH ↔ ADP + NADPH vertices: substrates edges: between all products / substrates

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

representations

ATP + NADH ↔ ADP + NADPH vertices: substrates + enzymes (reactions) edges: between substance / reaction vertices NADH kinase

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

representations

different representations, give different information most common representation = substance graphs—following atoms, the number of conversions between two molecules are small ⇔ the graph distance is small

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

representations

different representations, give different information most common representation = substance graphs—following atoms, the number of conversions between two molecules are small ⇔ the graph distance is small

slide-30
SLIDE 30

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

representations

different representations, give different information most common representation = substance graphs—following atoms, the number of conversions between two molecules are small ⇔ the graph distance is small

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

the dogmas of network science

real networks have both structure and randomness the network structure relates to the function of the network

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

the dogmas of network science

real networks have both structure and randomness the network structure relates to the function of the network

slide-33
SLIDE 33

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

the dogmas of network science

real networks have both structure and randomness the network structure relates to the function of the network

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what is network structure?

how the network differs a random network to be more precise: how the network differs from a null model

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SLIDE 35

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what is network structure?

how the network differs a random network to be more precise: how the network differs from a null model

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SLIDE 36

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

what is network structure?

how the network differs a random network to be more precise: how the network differs from a null model

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

network null-models

Network structures are relative . . . . . . so one has to be clear about what to compare with . . . a null model Null model 1: random graphs (Poisson random graphs, Erd˝

  • s-R´

enyi graphs) Null model 2: random graphs constrained to the set of degrees of the original graph

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

network null-models

Network structures are relative . . . . . . so one has to be clear about what to compare with . . . a null model Null model 1: random graphs (Poisson random graphs, Erd˝

  • s-R´

enyi graphs) Null model 2: random graphs constrained to the set of degrees of the original graph

slide-39
SLIDE 39

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

network null-models

Network structures are relative . . . . . . so one has to be clear about what to compare with . . . a null model Null model 1: random graphs (Poisson random graphs, Erd˝

  • s-R´

enyi graphs) Null model 2: random graphs constrained to the set of degrees of the original graph

slide-40
SLIDE 40

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

network null-models

Network structures are relative . . . . . . so one has to be clear about what to compare with . . . a null model Null model 1: random graphs (Poisson random graphs, Erd˝

  • s-R´

enyi graphs) Null model 2: random graphs constrained to the set of degrees of the original graph

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

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SLIDE 42

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

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SLIDE 43

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

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SLIDE 44

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

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SLIDE 45

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

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SLIDE 46

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

slide-47
SLIDE 47

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

slide-48
SLIDE 48

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

slide-49
SLIDE 49

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

slide-50
SLIDE 50

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

slide-51
SLIDE 51

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

slide-52
SLIDE 52

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random graphs with probability p, add an edge for each pair of vertices,

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SLIDE 53

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random rewiring start from the original graph choose edge pairs, and swap them

slide-54
SLIDE 54

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random rewiring start from the original graph choose edge pairs, and swap them

slide-55
SLIDE 55

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random rewiring start from the original graph choose edge pairs, and swap them

slide-56
SLIDE 56

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random rewiring start from the original graph choose edge pairs, and swap them

slide-57
SLIDE 57

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

random rewiring start from the original graph choose edge pairs, and swap them

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SLIDE 58

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

degree distribution

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

network structure of metabolism

Power-law degree distributions. Increasing average degree. Network modularity?

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

network structure of metabolism

Power-law degree distributions. Increasing average degree. Network modularity?

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

network structure of metabolism

Power-law degree distributions. Increasing average degree. Network modularity?

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

network structure of metabolism

Power-law degree distributions. Increasing average degree. Network modularity?

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

network structure of metabolism

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

network structure of metabolism

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity (of a partition)

Definition Q =

  • i

         eii −         

  • j

eij

        

2

        

(1) the sum is over the a partition into clusters and eij is the fraction of edges that leads between vertices of cluster i and j

1 2

Q ≈ 0.48

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity (of a graph)

Definition

ˆ

Q(G) = max

partitions Q

(2) (null model: random graphs) Definition

ˆ

Q(G) = max

partitions Q −

  • max

partitions Q

  • (3)

(null model: random graphs with the same degree sequence)

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity (of a graph)

Definition

ˆ

Q(G) = max

partitions Q

(2) (null model: random graphs) Definition

ˆ

Q(G) = max

partitions Q −

  • max

partitions Q

  • (3)

(null model: random graphs with the same degree sequence)

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity (the biological idea)

(Bhattacharyya et al., 2006, Annu. Rev. Biochem. 75, pp. 655–80)

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity (the biological idea)

(Bhattacharyya et al., 2006, Annu. Rev. Biochem. 75, pp. 655–80)

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity and robustness

robustness—sensitivity of a relevant dynamic system on the network to perturbations perturbations = changes in:

network topology concentrations delays in periodic input

in spreading of harmful things (like disease), modularity increases robustness in other systems where a flow is needed throughout the networks, modularity might decrease robustness

slide-71
SLIDE 71

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity and robustness

robustness—sensitivity of a relevant dynamic system on the network to perturbations perturbations = changes in:

network topology concentrations delays in periodic input

in spreading of harmful things (like disease), modularity increases robustness in other systems where a flow is needed throughout the networks, modularity might decrease robustness

slide-72
SLIDE 72

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity and robustness

robustness—sensitivity of a relevant dynamic system on the network to perturbations perturbations = changes in:

network topology concentrations delays in periodic input

in spreading of harmful things (like disease), modularity increases robustness in other systems where a flow is needed throughout the networks, modularity might decrease robustness

slide-73
SLIDE 73

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity and robustness

robustness—sensitivity of a relevant dynamic system on the network to perturbations perturbations = changes in:

network topology concentrations delays in periodic input

in spreading of harmful things (like disease), modularity increases robustness in other systems where a flow is needed throughout the networks, modularity might decrease robustness

slide-74
SLIDE 74

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity and robustness

robustness—sensitivity of a relevant dynamic system on the network to perturbations perturbations = changes in:

network topology concentrations delays in periodic input

in spreading of harmful things (like disease), modularity increases robustness in other systems where a flow is needed throughout the networks, modularity might decrease robustness

slide-75
SLIDE 75

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity and robustness

robustness—sensitivity of a relevant dynamic system on the network to perturbations perturbations = changes in:

network topology concentrations delays in periodic input

in spreading of harmful things (like disease), modularity increases robustness in other systems where a flow is needed throughout the networks, modularity might decrease robustness

slide-76
SLIDE 76

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity and robustness

robustness—sensitivity of a relevant dynamic system on the network to perturbations perturbations = changes in:

network topology concentrations delays in periodic input

in spreading of harmful things (like disease), modularity increases robustness in other systems where a flow is needed throughout the networks, modularity might decrease robustness

slide-77
SLIDE 77

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity and robustness

robustness—sensitivity of a relevant dynamic system on the network to perturbations perturbations = changes in:

network topology concentrations delays in periodic input

in spreading of harmful things (like disease), modularity increases robustness in other systems where a flow is needed throughout the networks, modularity might decrease robustness

slide-78
SLIDE 78

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity and robustness

modular redundancy (Kitano, 2004, Nat. Rev. Genet. 5, pp. 826–837.)

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity and robustness

distributed redundancy (A. Wagner): In distributed robustness, many parts of a system contribute to its function, but all of these parts have different roles. When one part fails or is changed through mutations, other parts can compensate for this failure, but not simply by standing in for the failed part.

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

currency metabolites

ATP g l u c

  • s

e g l u c

  • s

e 6 − P f r u c t

  • s

e 6 − P f r u c t

  • s

e 1 , 6 − P g l y c e r a l d e h y d e 3 − P 1 , 3 − P g l y c e r a t e 3 − P g l y c e r a t e 2 − P g l y c e r a t e p h

  • s

p h

  • e

n

  • l

p y r u v a t e p y r u v a t e

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Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

currency metabolites

Wagner & Fell, 2001 Schuster et al., 2002 Ma & Zeng, 2003 ATP ATP ATP ADP ADP ADP NADP NADP NADP NADPH NADPH NAD NAD NADH Pi Pi H2O H2O H+ PPi CMP CO2 O2 NH3

slide-82
SLIDE 82

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

currency metabolites (a definition)

1

currency metabolites have high degree

2

they make not meaningful shortcuts

3

i.e. tie together distant parts of the network

4

i.e. tie different modules together . . . let’s turn this around to a definition . . .

slide-83
SLIDE 83

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

currency metabolites (a definition)

1

currency metabolites have high degree

2

they make not meaningful shortcuts

3

i.e. tie together distant parts of the network

4

i.e. tie different modules together . . . let’s turn this around to a definition . . .

slide-84
SLIDE 84

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

currency metabolites (a definition)

1

currency metabolites have high degree

2

they make not meaningful shortcuts

3

i.e. tie together distant parts of the network

4

i.e. tie different modules together . . . let’s turn this around to a definition . . .

slide-85
SLIDE 85

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

currency metabolites (a definition)

1

currency metabolites have high degree

2

they make not meaningful shortcuts

3

i.e. tie together distant parts of the network

4

i.e. tie different modules together . . . let’s turn this around to a definition . . .

slide-86
SLIDE 86

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

currency metabolites (a definition)

1

currency metabolites have high degree

2

they make not meaningful shortcuts

3

i.e. tie together distant parts of the network

4

i.e. tie different modules together . . . let’s turn this around to a definition . . .

slide-87
SLIDE 87

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

currency metabolites (a definition)

1

currency metabolites have high degree

2

they make not meaningful shortcuts

3

i.e. tie together distant parts of the network

4

i.e. tie different modules together . . . let’s turn this around to a definition . . .

slide-88
SLIDE 88

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

currency metabolites (a definition)

Definition Remove vertices in order of (currently) highest degree. The set

  • f removed vertices that gives the network the highest

modularity is the set of currency metabolites.

slide-89
SLIDE 89

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

human currency metabolites

currency metabolites commodity metabolites number of deleted vertices ∆Q 0.08 0.10 0.12 0.14 0.16 10 30 40 20

slide-90
SLIDE 90

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

detected currency metabolites

Wagner & Fell, 2001 Schuster et al., 2002 Ma & Zeng, 2003 ATP ATP ATP ADP ADP ADP NADP NADP NADP NADPH NADPH NAD NAD NADH Pi Pi H2O H2O H+ PPi CMP CO2 O2 NH3

slide-91
SLIDE 91

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modularity and robustness

  • i. nitrogen metabolism
  • iv. citric acid cycle / porphyrin synthesis
  • vii. metabolism of xenobiotics

x.

  • ii. amino acid metabolism / protein synthesis
  • v. fatty acid metabolism
  • viii. tyrosine and tryptamine metabolism
  • xi. glycerophospholipid and arachidonic acid metabolism

sugar metabolism iii.

  • vi. steroid metabolism
  • ix. DNA metabolism / glycolysis

nucleoside / nucleotide metabolism commodity metabolites currency metabolites

i vii viii ix x iii ii xi v vi iv

slide-92
SLIDE 92

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

different organisms

  • rganism

samples nodes edges

  • c. m.

modularity animals 5 1621 4662 6.2 0.157 plants 1 1561 4302 1 0.144 fungi 2 1281 3654 1.5 0.150 bacteria 99 1050 2739 1.7 0.140

slide-93
SLIDE 93

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

conclusions

proposed graph based definition of currency metabolites metabolic networks are modular, but not so much the reason they are not more modular might be give robustness (Huss & Holme, 2007, IET Syst. Biol. 1, pp. 280–5.)

slide-94
SLIDE 94

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

conclusions

proposed graph based definition of currency metabolites metabolic networks are modular, but not so much the reason they are not more modular might be give robustness (Huss & Holme, 2007, IET Syst. Biol. 1, pp. 280–5.)

slide-95
SLIDE 95

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

conclusions

proposed graph based definition of currency metabolites metabolic networks are modular, but not so much the reason they are not more modular might be give robustness (Huss & Holme, 2007, IET Syst. Biol. 1, pp. 280–5.)

slide-96
SLIDE 96

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

conclusions

proposed graph based definition of currency metabolites metabolic networks are modular, but not so much the reason they are not more modular might be give robustness (Huss & Holme, 2007, IET Syst. Biol. 1, pp. 280–5.)

slide-97
SLIDE 97

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

conclusions

proposed graph based definition of currency metabolites metabolic networks are modular, but not so much the reason they are not more modular might be give robustness (Huss & Holme, 2007, IET Syst. Biol. 1, pp. 280–5.)

slide-98
SLIDE 98

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

subnetwork hierarchies

P . Holme, M. Huss & H. Jeong, 2003, Bioinformatics 19, pp. 532–8. Start with a directed bipartite networks, with both reaction and substance vertices (keep the currency metabolites). Iteratively remove the reaction vertices with the highest betweenness (fraction of shortest paths passing through a vertex). Study the dendrogram of this process.

( ) S2 h0 ( ) h0 S1 h h h0

max

slide-99
SLIDE 99

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

subnetwork hierarchies

P . Holme, M. Huss & H. Jeong, 2003, Bioinformatics 19, pp. 532–8. Start with a directed bipartite networks, with both reaction and substance vertices (keep the currency metabolites). Iteratively remove the reaction vertices with the highest betweenness (fraction of shortest paths passing through a vertex). Study the dendrogram of this process.

( ) S2 h0 ( ) h0 S1 h h h0

max

slide-100
SLIDE 100

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

subnetwork hierarchies

P . Holme, M. Huss & H. Jeong, 2003, Bioinformatics 19, pp. 532–8. Start with a directed bipartite networks, with both reaction and substance vertices (keep the currency metabolites). Iteratively remove the reaction vertices with the highest betweenness (fraction of shortest paths passing through a vertex). Study the dendrogram of this process.

( ) S2 h0 ( ) h0 S1 h h h0

max

slide-101
SLIDE 101

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

subnetwork hierarchies

P . Holme, M. Huss & H. Jeong, 2003, Bioinformatics 19, pp. 532–8. Start with a directed bipartite networks, with both reaction and substance vertices (keep the currency metabolites). Iteratively remove the reaction vertices with the highest betweenness (fraction of shortest paths passing through a vertex). Study the dendrogram of this process.

( ) S2 h0 ( ) h0 S1 h h h0

max

slide-102
SLIDE 102

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

shell- vs community-type ordering

(a) (b)

slide-103
SLIDE 103

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

dendrogram

(b) (a)

slide-104
SLIDE 104

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modules

CoA D−glucosamine 1−phosphate −acetyldihydrolipoamide acetyl−CoA dihydrolipoamide deoxyguanosine 2−deoxy−D−ribose 1−phosphate deoxyadenosine guanine guanosine −D−ribose 1−phosphate adenine adenosine hypoxanthine inosine

  • rthophosphate

−D−ribose 1−pyrophosphate −acetyl−D−glucosamine 1−phosphate α α S N

iii ii i

slide-105
SLIDE 105

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modules

α N α S H O

2

pyruvate, CO2 H O

2

CO2 ATP, ADP pyrophosphate NADPH, NADH substrate reaction node link in−flow

  • ut−flow

−D−ribose 1−phosphate CoA

  • rthophosphate

adenine deoxyadenosine inosine adenosine hypoxanthine guanine guanosine deoxyguanosine D−glucosamine 1−phosphate 1−phosphate −acetyl−D−glucosamine acetyl−CoA dihydrolipoamide −D−ribose 1−pyrophosphate −acetyldihydrolipoamide pyrophosphate 2−deoxy−D−ribose 1−phosphate iii ii i

slide-106
SLIDE 106

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modules

primosome complex 5.99.1.3.DNA topoisomerase II 2.7.7.7.DNA polymerase III DNA helicase II 2.7.7.7.DNA polymerase I SSB

  • pen prepriming complex

6.5.1.2.DNA ligase Rep 5.99.1.2.DNA topoisomerase I −phosphohistidine

p

N −phosphohistidine −phosphohistidine N HPr proteinN−pros− phosphohistidine

p

N enzyme IIIGlc enzyme IIIMan enzyme IIIScr enzyme IIIMan

Glc

enzyme III

p

N enzyme IIIFru

Scr

enzyme III enzyme IIIFru −phosphohistidine HPr protein histidine

p

slide-107
SLIDE 107

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

modules

pyruvate −phosphohistidine −phosphohistidine enzyme IIIGlc

p

N enzyme IIIFru

p

N −phosphohistidine enzyme IIIScr

p

N enzyme IIIMan enzyme IIIMan enzyme IIIGlc enzyme IIIFru HPr protein phosphohistidine N−pros− enzyme IIIScr

p

N −phosphohistidine phosphoenolpyruvate CTP GTP

  • rtophosphate

ATP ADP SSB DNA helicase II 6.5.1.2.DNA ligase 2.7.7.7.DNA polymerase I

  • pen prepriming complex

Rep prepriming complex RNA primer−primosome complex UTP

  • rtophosphate

5.99.1.2.DNA topoisomerase I 2.7.7.7.DNA polymerase III HPr protein histidine primosome complex 5.99.1.3.DNA topoisomerase II

slide-108
SLIDE 108

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

dentrogram statistics

0.2 0.4 0.6 0.8 1 0.2 0.4 0.6 0.8 1 S1 ~

2

~ S S1/ S2 10 20 30 40 80 120 160 5 10 15 20 25 30 20 40 60 80 10 20 30 40 50 60 70 50 100 150 200 250 h h h h h h 0.2 0.4 0.6 0.8 1 0.2 0.4 0.6 0.8 1 , , S2 S1/ S2 S1 ~ ~ , , S2 S1/ S2 S1 ~ ~ , , S2 S1/ S2 S1 ~ ~ , , S2 S1/ S2 S1 ~ ~

(b) (c)

(f)

(e) (d) (a)

slide-109
SLIDE 109

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

conclusions

Shell- rather than community-type ordering A few, seemingly clear, modules

slide-110
SLIDE 110

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

conclusions

Shell- rather than community-type ordering A few, seemingly clear, modules

slide-111
SLIDE 111

Network modularity, currency metabolites and graph representa- tions of metabolism PETTER HOLME metabolic networks, intro networks (physicist style?) modularity & currency metabolites subnetwork hierarchies

conclusions

Shell- rather than community-type ordering A few, seemingly clear, modules