Evidence for dynamically organized modularity in the yeast protein-protein interaction network

1. Evidence for dynamically organized modularity in the yeast protein-protein interaction network Han, et al. 2004

2. Preprocessing 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 different data sources • 1,397 proteins • A large connected component of 778 proteins

4. Network of the connected component of 778 proteins

5. 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

6. Power law distribution

7. 37 ribosomal proteins highlighted

8. Expression correlation • Hubs of PPI network • Nodes with degree k greater than 5 • mRNA expression data set of 315 conditions • Five categories of conditions • Average PPCs between the hub and each of its respective partners Pearson correlation coefficient

9. Red curve: average PCCs of hubs Cyan curve: average PCCs of non-hubs Black curve: average PCCS of hubs in randomized networks

10. Party and date hubs • The bimodal distribution suggests that hubs can be split into two distinct populations: • One with relatively high average PCCs (108 party hubs) • The other with relatively low average PCCs (91 date hubs)

11. Categories according to YPD annotations

12. Partners of date hubs are significantly more diverse in spatial distribution than partners of party hubs, according to proteome-wide cellular localization data set.

13. Gradual removal of nodes Green line: random removal of nodes; Brown line: attack on all hubs; Blue line: attack on party hubs; Red line: attack on date hubs; The characteristic path length, defined as the average distance (shortest path length) between node pairs, reflects the overall network connectivity.

14. The largest connected component of the FYI network Removal of date hubs Removal of party hubs

15. Removal of hubs

16. Sub-networks released by date hub removals are more homogeneous in function

17. Sub-networks released by date hub removals are more homogeneous in function

18. Two types of sub-networks: • Stable molecular machines or complexes • Loosely connected regulatory pathways

19. 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.

20. Genetic perturbations Essentiality GID: genetic interaction density, measures the participation of a protein in genetic interactions.

21. The End