The LargeScale Organization of Metabolic Networks

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The Large-Scale Organization of Metabolic
Networks
H. Jeong, B. Tombor, R. Albert, Z.N. Oltvai,
A.-L. Barabási (2000) Nature 407651-654

• S-114.220, Spring 05
• Margareta Segerståhl

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Metabolism?

• the processes that keep active cells alive and
  kicking
• Energy in, waste out
• Building material for growth and differentiaton
• Movement, communication
• etc.
• Complex network of cellular constituents and
  reactions

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Aim of the Study

• Large-scale structure of metabolic networks not
  known
• Jeong et al. performed a systematic comparative
  mathematical analysis of the metabolic networks
  of 43 organisms.
• Used data deposited in the WIT database

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WTI database 5 years ago

• DB subgroups
• 1) Metabolism energetics
• 2) Information pathway
• 3) Electron transport
• 4) Transmembrane transport
• 5) Signal transduction
• 6) Structure function of cell

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WTI Database

• predicts the existence of a given metabolic
  pathway on the basis of the
• 1) Annotated genome of an organism
• combined with
• 2) Solid data from biochemical literature.
• It is the information about the enzymes that can
  be found from the sequenced genome.
• Enzymes determine what chemical reactions are
  possible in principle

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Enzymes driving the reactions can be included as
number codes e.g. 1.3.2.3.
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Example (reaction in one direction)
Enzyme(E1)
Educt (S1)
Product (S3)
Temporary Complex (M1)
Educt (S2)
Product (S4)
Obtain following connectivity information for
adjacency matrix
S1 ?M1-E1, S2 ? M1-E1, M1-E1 ? S3,
M1-E1 ? S4.
Substrates are nodes, Reactions are links, have
direction.
S1 S2 S3 S4 M1 E1 S1 0 0 0 0 1 0 S2 0
0 0 0 1 0 S3 0 0 0 0 0 0 S4 0 0 0 0
0 0 M1 0 0 1 1 0 1 E1 0 0 0 0 1 0
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Connectivity

• Connectivity
• distribution,
• P(k) in out.
• -Probability that a given substrate participates
  in k reactions follows a
• power law distribution.

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Other Network Measures

• a) Pathway lengths ?
• b) Diameter D
• c,d) Average of in/out links per node
• e) Effect of removing hubs / random nodes
• f) Substrate ranking

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Substrates
total of links in/out
reactions/temporary complexes
Enzymes
Exponents
Diameter
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Who are the hubs?
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Who are the hubs?
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17 C. acetobutylicum 494 abcdgefhlk adbceijhfo 18
M. genitalium 209 bdcgzxuyos adbcguvwos 19 M.
pneumoniae 178 bcdgxoyasl dabcgowvsr 20 S.
pneumoniae 416 abdcgelfno adbceifghj 21 S.
pyogenes 403 abdcegfoln adbceifohg 22 C.
tepidum 389 badcgenfki dabceipgfq 23 R.
capsulatus 670 abcdhgefjk adbjhicmet 33 H.
influenzae 526 abcdegfjhm adbchiefju 34 P.
aeruginosa 734 abdchjkgef adjhbimcef 35 T.
pallidum 207 bdcgaelnfh dabcegiplf 36 B.
burgdorferi 187 bdgcaleifn dabcgifeal 37 T.
maritima 338 badcegfikn dabceifgqh 38 D.
radiodurans 815 acbdhjgekm adhbjcimef 39 E.
nidulans 383 abdcegjhfl adbcjheifq 40 S.
cerevisiae 561 abdcehjgkm adbhcjeifm 41 C.
elegans 462 abdcjhelgk adbhcjiefm 42 O. sativa
292 badcegljkn adbcehjifn 43 A. thaliana 302
badcegjhlk adbcehjign
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