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Evidence for dynamically organized Evidence for dynamically organized modularity in the yeast protein-modularity in the yeast protein-protein interaction networkprotein interaction network
Han, et al. 2004
Preprocessing of PPI dataPreprocessing of PPI data
• Data sources:• Yeast two-hybrid data (5,249)• Affinity purifications followed by MS (6,630)• Computational predications (7,446)• MIPS protein complexes (9,597)
• FYI (Filtered Yeast Interactome):• 2,493 interactions, each observed in at least two di
fferent data sources• 1,397 proteins• A large connected component of 778 proteins
Network of the connected component of 778 proteins
• ribosomal protein L23a.e• TFIID and SAGA subunit• 60S large subunit ribosomal protein L5.e• 60S large subunit ribosomal protein L27a.e• 60S large subunit ribosomal protein L8.e• 60S large subunit ribosomal protein L3.e• 60S large subunit ribosomal protein• 60S large subunit ribosomal protein• 60S large subunit ribosomal protein• 60S large subunit ribosomal protein• 60S large subunit ribosomal protein
Power law distribution
37 ribosomal proteins highlighted
Expression correlationExpression correlation
• Hubs of PPI network• Nodes with degree k gre
ater than 5• mRNA expression data
set of 315 conditions• Five categories of conditi
ons• Average PPCs between
the hub and each of its respective partners
1
2 2
1 1
( )( )
( ) ( )
n
i ii
xy n n
i ii i
x x y yPCC
x x y y
Pearson correlation coefficient
Red curve: average PCCs of hubsCyan curve: average PCCs of non-hubsBlack curve: average PCCS of hubs in randomized networks
Party and date hubsParty and date hubs
• The bimodal distribution suggests that hubs can be split into two distinct populations: • One with relatively high a
verage PCCs (108 party hubs)
• The other with relatively low average PCCs (91 date hubs)
Date hubs Party hubs Date % Party %
Total 91 108 100% 100%
Regulator 45 13 49% 12%
Adaptor 15 6 16% 6%
Mediator 10 0 11% 0%
Complex 16 87 18% 81%
Other 3 2 3% 2%
unclear 2 0 2% 0%
Categories according to YPD annotations
• Partners of date hubs are significantly more diverse in spatial distribution than partners of party hubs, according to proteome-wide cellular localization data set.
Gradual removal of nodes
The characteristic path length, defined as the average distance (shortest path length) between node pairs, reflects the overall network connectivity.
Green line: random removal of nodes;Brown line: attack on all hubs;Blue line: attack on party hubs;Red line: attack on date hubs;
Removal of date hubs Removal of party hubs
The largest connected component of the FYI network
Removal of hubs Removal of hubs
Sub-networks released by date hub Sub-networks released by date hub removals are more homogeneous in removals are more homogeneous in functionfunction
Sub-networks released by date hub Sub-networks released by date hub removals are more homogeneous in removals are more homogeneous in functionfunction
• Two types of sub-networks:• Stable molecular machines or complexes• Loosely connected regulatory pathways
Organized modularity model:•date hubs represent global, or ‘higher level, connectors between modules•party hubs function inside modules, at a ‘lower level’ of the organization of the proteome.
Genetic perturbations Genetic perturbations
Essentiality
GID: genetic interaction density, measures the participation of a protein in genetic interactions.
The End