Dynamic modular architecture of protein-protein interaction networks beyond the dichotomy of date and party hubs

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1 Dynamic modular architecture of protein-protein interaction networks beyond the dichotomy of date and party hubs Xiao Chang 1,#, Tao Xu 2,#, Yun Li 3, Kai Wang 1,4,5,* 1 Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, USA 2 Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany 3 Key Laboratory of Systems Biology, Chinese Academy of Sciences, Shanghai, China 4 Department of Psychiatry, Keck School of Medicine, University of Southern California, Los Angeles, USA 5 Division of Bioinformatics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA # These authors contributed equally to this work * Correspondence should be addressed to: kaiwang@usc.edu

2 Supplementary Figures and Tables Figure S1. Comparison of the modules identified between filtered-hc and updated-hc

3 Figure S2 avpcc distributions of node roles. UHC, Updated-HC; FHC, Filtered-HC.

4 Figure S3. A) Distribution of the avpcc in 23 modules of Filtered-HC. Module 4 displays a clearly bimodal pattern and the higher peak is above 0.5 indicating a large proportion of genes in module 4 are highly coexpressed.

5 Figure S3. B) Distribution of the avpcc in 14 modules of Updated-HC. Module 12 in Updated-HC shares a great number of genes with module 4 in Filter-HC, so they represent analogue patterns of avpcc distribution.

6 Figure S4. A) Plot of dn/ds versus avpcc from all data set. There is a negative correlation between the two measurements (Pearson correlation coefficient=-0.23, p-value < 2.2e-16). Gene functional categories are marked. Red, ribosome biogenesis and assembly; green, DNA metabolism; orange, RNA metabolism.

7 Figure S4. B) Plot of dn/ds versus avpcc from module 4. There is a negative correlation between the two measurements (Pearson correlation coefficient=-0.32, p-value < 2.02e-4). Gene functional categories are marked. Red, ribosome biogenesis and assembly; green, DNA metabolism; orange, RNA metabolism.

8 Figure S5. Comparison of the dn/ds distribution among proteins from total data set, module 4 and enriched functions of module 4

9 Figure S6. Plot of role assignments and avpcc. Role assignments: R1, Ultra-peripheral; R2, Peripheral; R3, Non-hub connector; R4, Non-hub kinless; R5, Provincial hub; R6, Connector hub; and R7, Kinless hub.

10 Figure S7 A). Distribution of the avpcc in human normal tissue

11 Figure S7 B). Distribution of the avpcc in human brain tissues

12 Figure S7 C). Distribution of the avpcc in human primary tumor

13 Table S1. Statistic of the basic network properties filtered-hc updated-hc Node Edge Degree Node_LCC Edge_LCC Degree_LCC *LCC: the largest connected component

14 Table S2. Overlap coefficients of modules identified in filtered-hc and updated-hc The overlap coefficient is defined as: UHC1 UHC2 UHC3 UHC4 UHC5 UHC6 UHC7 UHC8 FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC FHC Module size

15 UHC9 UHC10 UHC11 UHC12 UHC13 UHC14 Module size

16 Table S3. Functional enrichment of modules identified in filtered-hc and updated-hc Functional enrichment of modules identified in Filtered-HC amino acid and derivative metabolism biological_process unknown carbohydrate metabolism cell-wall-and-membrane organization and biogenesis E-05 cell budding and cytokinesis E-10 cell cycle cell homeostasis cellular respiration conjugation cytoskeleton organization and biogenesis DNA metabolism generation of precursor metabolites and energy lipid metabolism meiosis morphogenesis nuclear organization and biogenesis E organelle organization and biogenesis E-09 protein biosynthesis and catabolism protein modification pseudohyphal growth response to stress ribosome biogenesis and assembly E RNA metabolism E signal transduction sporulation transcription E transport vitamin metabolism

17 E E E E E E E E E E E E E

18 E E E E E E

19 Functional enrichment of modules identified in Updated-HC amino acid and derivative metabolism biological_process unknown carbohydrate metabolism cell-wall-and-membrane organization and biogenesis cell budding and cytokinesis cell cycle 3.83E cell homeostasis cellular respiration conjugation cytoskeleton organization and biogenesis E DNA metabolism generation of precursor metabolites and energy lipid metabolism meiosis morphogenesis nuclear organization and biogenesis E organelle organization and biogenesis protein biosynthesis and catabolism protein modification pseudohyphal growth 3.63E response to stress ribosome biogenesis and assembly RNA metabolism signal transduction 1.46E sporulation transcription transport 3.70E vitamin metabolism

20 E E E E E E E E E E

21 Table S4.Functional enrichment of modules identified in Human interactome. Only the modules containing more than 40 genes were listed. Table S5. Details of the node role assignment, module classification and function annotation

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