topology of the protein network h. jeong, s.p. mason, a.-l. barabasi, z.n. oltvai, nature 411, 41-42...
TRANSCRIPT
Topology of the protein network
H. Jeong, S.P. Mason, A.-L. Barabasi, Z.N. Oltvai, Nature 411, 41-42 (2001)
Erdös-Rényi model (1960)
- Democratic
- Random
Pál ErdösPál Erdös (1913-1996)
Connect with probability p
p=1/6 N=10
k ~ 1.5
Degree distribution of a random graph
P(k): the probability that a node has k links
P(k)= Ck N-1 p
k (1-p)N-1-k
For large N P(k) can be replaced by a Poisson distribution:
P(k)~ e-<k> <k>k/k!
Poisson distribution
World Wide Web
Over 3 billion documentsROBOT: collects all URL’s found in a document and follows them recursively
Nodes: WWW documents Links: URL links
R. Albert, H. Jeong, A-L Barabasi, Nature, 401 130 (1999).
Exp
ected
P(k) ~ k-
Fou
nd
Sca
le-f
ree
Netw
ork
Exp
on
en
tial
Netw
ork
Scale-free model
Barabási & Albert, Science 286, 509 (1999)
jj
ii k
kk
)(
P(k) ~k-3
(1) Networks continuously expand by the addition of new nodesWWW : addition of new documents Citation : publication of new papers
GROWTH: add a new node with m links
PREFERENTIAL ATTACHMENT: the probability that a node connects
to a node with k links is proportional to k.
(2) New nodes prefer to link to highly connected nodes.
WWW : linking to well known sites Citation : citing again highly cited papers
Other Models
Internet
Metabolic network
Organisms from all three domains of life are scale-free networks!
H. Jeong, B. Tombor, R. Albert, Z.N. Oltvai, and A.L. Barabasi, Nature, 407 651 (2000)
Archaea Bacteria Eukaryotes
http://www.orgnet.com
Many real world networks have a similar architecture:
Scale-free networks
WWW, Internet (routers and domains), electronic circuits, computer software, movie actors, coauthorship networks, sexual web, instant messaging, email web, citations, phone
calls, metabolic, protein interaction, protein domains, brain function web, linguistic networks, comic book
characters, international trade, bank system, encryption trust net, energy landscapes, earthquakes, astrophysical
network…
Copyright ©2002 American Society for Biochemistry and Molecular BiologyCopyright ©2002 American Society for Biochemistry and Molecular Biology
Deane, C. M. (2002) Mol. Cell. Proteomics 1: 349-356Deane, C. M. (2002) Mol. Cell. Proteomics 1: 349-356
Interacting yeast proteins as detected in several studiesInteracting yeast proteins as detected in several studies
L.Salwinski & D.Eisenberg. Curr.Op.Struct.Biol. 13 (2003)L.Salwinski & D.Eisenberg. Curr.Op.Struct.Biol. 13 (2003)
J.S. Bader et al.. Nature Biotechnology 22 (2004)J.S. Bader et al.. Nature Biotechnology 22 (2004)
Filtered Yeast Interactome dataset Filtered Yeast Interactome dataset (Han et al., Nature 430, 2004)(Han et al., Nature 430, 2004) (HT-Y2H) projects (HT-Y2H) projects (5,249 potential interactions - union of the available data sets)(5,249 potential interactions - union of the available data sets)
Co-IP Co-IP (6,630 potential interactions from two datasets) (6,630 potential interactions from two datasets)
in silicoin silico computational predictions of interactions computational predictions of interactions (7,446 potential interactions from the 'von Mering' data set (7,446 potential interactions from the 'von Mering' data set obtained from the union of gene co-occurrence, gene obtained from the union of gene co-occurrence, gene neighbourhood and gene fusion predictions)neighbourhood and gene fusion predictions)
'MIPS protein complexes' published singly in the literature 'MIPS protein complexes' published singly in the literature (9,597 pairwise interactions between components of complexes(9,597 pairwise interactions between components of complexes
MIPS physical interactions MIPS physical interactions (excluding genome-scale experiments: 1,285 interactions).(excluding genome-scale experiments: 1,285 interactions).
J-D. Han et al. Nature 430 (2004)J-D. Han et al. Nature 430 (2004)
•UNIPROT DATABASE UNIPROT DATABASE filtered by SEGfiltered by SEG
VirusesViruses
BacteriaBacteria
ArchaeaArchaea
AscomycotaAscomycota
MetazoaMetazoa
SpermatophytaSpermatophyta
BLASTPBLASTPS. CerevisiaeS. Cerevisiae sequence as a query sequence as a query
BACTERIA
METAZOA
VIRUSES
1010-4-4
11ARCHAEA
ARCHAEA
Top scoring sequences from each group Top scoring sequences from each group parwise SW homology check with 100 randomisations and Z-score cutoff parwise SW homology check with 100 randomisations and Z-score cutoff
A-L. Barabasi & Z.N. Oltvai. Nature Reviews Genetics 5 (2004)A-L. Barabasi & Z.N. Oltvai. Nature Reviews Genetics 5 (2004)
A-L. Barabasi & Z.N. Oltvai. Nature Reviews Genetics 5 (2004)A-L. Barabasi & Z.N. Oltvai. Nature Reviews Genetics 5 (2004)
Archaea, Eubacteria, Fungi, Plants, Animals (33/26)Archaea, Eubacteria, Fungi, Plants, Animals (33/26)
protein synthesis mprotein synthesis machinery (40S and 60S ribosomachinery (40S and 60S ribosomal subunitsal subunits, ,
translational factorstranslational factors, , t-RNA synthetases t-RNA synthetases
bbasic metabolismasic metabolism (e.g. ATP (e.g. ATP synthesis , synthesis , KrebsKrebs cycle cycle))
protein folding and degradation (cprotein folding and degradation (chaperoneshaperones, proteases), proteases)
domains participating in protein-protein interactionsdomains participating in protein-protein interactions (TP(TPRR, ,
WD40)WD40) +Viruses (16/5)+Viruses (16/5)
replication (RNA polymerases, helicases, replication factor C, replication (RNA polymerases, helicases, replication factor C,
ribonucleotide reductase)ribonucleotide reductase)
protein degradation (19S proteasome)protein degradation (19S proteasome)
40S ribosome40S ribosome Mitochondrial ribosomalMitochondrial ribosomal40S subunit40S subunit
S. Wuchty, Z.N. Oltvai & A-L. Barabasi. Nature Genetics 22 (2003)S. Wuchty, Z.N. Oltvai & A-L. Barabasi. Nature Genetics 22 (2003)
Mitochondrial alpha-ketoglutarateMitochondrial alpha-ketoglutaratedehydrogenase and pyruvate dehydrogenase and pyruvate
degydrogenase complexesdegydrogenase complexes Succinate dehydrogenaseSuccinate dehydrogenase
General repressor of transcriptionGeneral repressor of transcription
CoatomerCoatomer NuclearNuclear
poreporeAnaphase-promoting complexAnaphase-promoting complex
(ubiquitin-protein ligase)(ubiquitin-protein ligase)Cyclophilin, heat shock protein Cyclophilin, heat shock protein
(HSP82) and STI1 inhibitor(HSP82) and STI1 inhibitor
Eubacteria, EukaryotaEubacteria, Eukaryota | |Archaea Archaea (4/4)(4/4)
catalytic core delta subunit of mitochondrial ATP-asecatalytic core delta subunit of mitochondrial ATP-ase
tubulintubulin (BtubA/B (BtubA/B - -ProsthecobacterProsthecobacter )
mitochondrial subunits of 60S ribosomemitochondrial subunits of 60S ribosome
RNA-binding proteins (cleavage factor I)RNA-binding proteins (cleavage factor I)
Mitochondrial ribosomalMitochondrial ribosomalproteins of the 60S subunitproteins of the 60S subunit
Central stalk Central stalk of mitochondrial of mitochondrial
F1F0 ATP synthaseF1F0 ATP synthase
Subunits of cleavage factor I (HRP1, RNA15), Subunits of cleavage factor I (HRP1, RNA15), poly-A binding protein (PAB1, SGN1), poly-A binding protein (PAB1, SGN1),
uncharacterized protein YGR250Cuncharacterized protein YGR250C
Alpha- andAlpha- andbeta-tubulinbeta-tubulin
Archaea, EukaryotaArchaea, Eukaryota | | Eubacteria Eubacteria (8/8)(8/8)
RNA polymerase II (non-catalyticRNA polymerase II (non-catalytic subunits)subunits)
60S ribosomal subunits (cytoplasmatic)60S ribosomal subunits (cytoplasmatic)
splicing (archeal-like LSM proteins)splicing (archeal-like LSM proteins)
exosome 3’exosome 3’5’ exoribonuclease complex5’ exoribonuclease complex
20S proteasome 20S proteasome
Protein components of large 60S ribosome subunitProtein components of large 60S ribosome subunit Subunits of RNA polymerase IISubunits of RNA polymerase II
EukaryotaEukaryota || Archaea, Eubacteria, Archaea, Eubacteria, Viruses Viruses (24/19)(24/19)
vesicle transport and membrane fusionvesicle transport and membrane fusion (multicompartmental cell)(multicompartmental cell)
mitochondrial transportersmitochondrial transporters
regulation of actin cytosregulation of actin cytoskkeleton stabilityeleton stability
Actin cytoskeleton Actin cytoskeleton regulating complexregulating complex
Actin capping heterodimerActin capping heterodimer Cofilin like protein and adenylylCofilin like protein and adenylylcyclase-asssociated proteincyclase-asssociated protein
Mitochondrial inner membrane ATP/ADP translocatorMitochondrial inner membrane ATP/ADP translocatorand mitochondrial inner membrane transporters (TIM22, TIM9, MRS1)and mitochondrial inner membrane transporters (TIM22, TIM9, MRS1)
Mitochondrial transport systemMitochondrial transport system
M.C. Rivera & J.A.Lake Nature 431 (2004)M.C. Rivera & J.A.Lake Nature 431 (2004)
M.C. Rivera & J.A.Lake Nature 431 (2004)M.C. Rivera & J.A.Lake Nature 431 (2004)
M.C. Rivera & J.A. Lake Nature 431 (2004)M.C. Rivera & J.A. Lake Nature 431 (2004)
44
2424
88
4949
L.Giot et al. Science. 2003, 302 (2003)
Subunits of 26 S proteasome comlexSubunits of 26 S proteasome comlex
Trehalose-6-phosphate complexTrehalose-6-phosphate complex
0.1
1
10
100
1000
10000
1 10 100 1000
nk
k
PL
GPL+EC
27.131065.1 knk
)0.3/exp()3.0(104.2 5.03 kknk
The number of S. cerevisiae proteins
The node degree
0
200
400
600
800
0 0.25 0.5 0.75 1 1.25.i
+- s.e.
Ai
Linear combination of exponential decays method:
)exp(max_
0
kAn i
i
iik
„S”
„F”
)exp()exp( kAkAn SSFFk
0.01
0.1
1
10
100
1000
10000
1 10 100 1000
nk
k
DEL
0
500
1000
1500
2000
2500
3000
0 1 2 3 4 5 6 7 8 10 11 12 13 14 15
nkF, nkS
k
F
S
The contribution of “F” and “S” component
050
100150200250300
0 5 10 15 20
Helicobacter pylorink
k
050
100150200250300
0 5 10 15 20
Escherichia colink
k
0
500
1000
1500
2000
0 5 10 15 20
Saccharomyces cerevisiaenk
k
0500
10001500200025003000
0 5 10 15 20
Drosophila melanogasternk
k
0
500
1000
1500
2000
0 5 10 15 20
Caenorhabditis elegansnk
k
0
50
100
150
200
250
0 5 10 15 20
Arabidopsis thalianank
k
0
100
200
300
400
500
0 5 10 15 20
Saccharomyces cerevisiaenk
k
PL
GPL+ECDEL
AICc = 94.6
AICc = 135.8
AICc = 112.4
1
)1(22)ln( 2
mz
mmmzAICc
Akaike's Information Criterion (AICc)
- the average squared residual for a given model, m - the number of the model parameters, z - the number of observations
2
E. coli23%
H. pylori71%
A. thaliana61%
37% C. elegans
D. melanogaster68%
S. cerevisiae74%
Interacting proteins