title title. Robustness, clustering & evolutionary conservation. Stefan Wuchty Center of Network Research Department of Physics University of Notre Dame. New York Times. Complex systems. Made of many non-identical elements connected by diverse interactions. NETWORK. Bio-Map. GENOME.
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Robustness, clustering &evolutionary conservation
Center of Network Research
Department of Physics
University of Notre Dame
Made of many non-identical elements connected by diverse interactions.
Yeast protein network
Links: physical interactions (binding)
P. Uetz, et al. Nature, 2000; Ito et al., PNAS, 2001; …
Topology of the protein network
H. Jeong, S.P. Mason, A.-L. Barabasi & Z.N. Oltvai, Nature, 2001
Fraction of removed nodes, f
Complex systems maintain their basic functions even under errors and failures (cell mutations; Internet router breakdowns)
Topological error tolerance
3 : fc=1
(R. Cohen et. al., PRL, 2000)
Robustness of scale-free networks
R. Albert et.al.
Yeast protein network
- lethality and topological position -
Highly connected proteins are more essential (lethal)...
H. Jeong et al., Nature, 2001
Modules in biological systems
E. Ravasz et al.,Science, 2002
J(i,j): # of nodes both i and j link to; +1 if there is a direct (i,j) link
Metabolism: E. Ravasz et al.,Science, 2002
Protein interactions: Rives and Galitski, PNAS, 2003
Spirin and Mirny, PNAS, 2003
Does the application of standart clustering
algorithms reflect real modules well?
Since e.g. one protein can be part of more
than one protein complex overlapping
clustering algorithms should give better
Small subnetworks that appear in real world networks significantly more often than in random graphs.
(Milo et al., Science, 2002; Conant and Wagner, Nature Gen., 2003, Shen-Orr et al., Nature Gen., 2002, Milo et al, Science, 2004)
A.-L- Barabasi & Z. Oltvai, Science, 2002
S. Wuchty, Z. Oltvai & A.-L. Barabasi, Nature Genetics, 2003
- General distribution of orthologs:
E = N(o)/N(p)
- degree-dependent distribution
ek = Nk(o)/Nk
Orthologous Excess Retention:
ERk = ek/E
S. Wuchty, Genome Res., 2004
high clustering = high quality of interaction
Goldberg and Roth, PNAS, 2003
are highly flawed:
90% false positives, 50% false negatives
Von Mering et al., Nature, 2002
How stable are these results?
Eisen et al., PNAS, 1998
Wuchty et al., submitted, 2004
until a maximum is reached.Inferred protein interaction networkin P. falciparum
All edges shown with C linkvw > 1.
Colorcode red: Cvw > 4, yellow: Cvw > 3,
green: Cvw > 2, blue: Cvw > 1
Bozdech et al. PLoS, 2003
What does that mean?
Validation of results?
Wuchty, Barabasi, Ferdig and Adams, in preperation