evidence for dynamically organized modularity in the yeast protein- protein interaction network han,...

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