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
Supplementary Figures and Tables Figure S1. Comparison of the modules identified between filtered-hc and updated-hc
Figure S2 avpcc distributions of node roles. UHC, Updated-HC; FHC, Filtered-HC.
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.
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.
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.
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.
Figure S5. Comparison of the dn/ds distribution among proteins from total data set, module 4 and enriched functions of module 4
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.
Figure S7 A). Distribution of the avpcc in human normal tissue
Figure S7 B). Distribution of the avpcc in human brain tissues
Figure S7 C). Distribution of the avpcc in human primary tumor
Table S1. Statistic of the basic network properties http://bionas.usc.edu/pdhub/table_s1.xls filtered-hc updated-hc Node 2561 4011 Edge 5992 10055 Degree 2.34 2.51 Node_LCC 2233 3801 Edge_LCC 5750 9742 Degree_LCC 2.58 2.56 *LCC: the largest connected component
Table S2. Overlap coefficients of modules identified in filtered-hc and updated-hc http://bionas.usc.edu/pdhub/table_s2.xls The overlap coefficient is defined as: UHC1 UHC2 UHC3 UHC4 UHC5 UHC6 UHC7 UHC8 FHC1 0 0.032258 0.182796 0.064516 0.526882 0.021505 0 0.021505 FHC2 0.168831 0.032468 0.564935 0.045455 0.02521 0.012987 0 0.012987 FHC3 0.005618 0.039326 0.016854 0.08427 0.008403 0.005618 0 0.707865 FHC4 0.066079 0.026432 0.105727 0.039648 0 0.004405 0 0.035242 FHC5 0.017241 0 0 0.017241 0 0.103448 0.017241 0 FHC6 0.029851 0.353234 0.243781 0.034826 0.008403 0.089552 0.020134 0.00995 FHC7 0.032609 0.228261 0.01087 0.032609 0.01087 0.01087 0.586957 0 FHC8 0.007194 0.014388 0.007194 0.021583 0 0.086331 0 0.035971 FHC9 0.350267 0.042781 0.058824 0.104956 0.151261 0.103352 0.006711 0.022801 FHC10 0 0 0 0 0 0.707317 0 0 FHC11 0.569767 0.069767 0.017442 0.081395 0.02521 0.052326 0.026846 0 FHC12 0.081633 0 0.102041 0.122449 0.020408 0 0 0 FHC13 0.09009 0 0.009009 0 0 0.018018 0.009009 0 FHC14 0.012658 0.012658 0 0.088608 0.025316 0 0.21519 0.025316 FHC15 0 0 0.04 0.12 0 0.56 0 0.08 FHC16 0.011905 0.166667 0.202381 0.119048 0.02381 0.095238 0.035714 0.047619 FHC17 0.321429 0 0.071429 0 0 0 0.071429 0 FHC18 0 0 0 0 0 0 0 1 FHC19 0 0 0 0 0 0 0 1 FHC20 1 0 0 0 0 0 0 0 FHC21 0 0.030769 0.015385 0.707692 0 0 0 0.015385 FHC22 0 0.142857 0 0.809524 0 0 0.047619 0 FHC23 0 0 0.142857 0 0 0.714286 0 0 Module size 410 431 488 343 119 358 149 307
UHC9 UHC10 UHC11 UHC12 UHC13 UHC14 Module size 0.075269 0.032258 0.010753 0.021505 0 0 93 0.058442 0.012987 0 0.006494 0.025974 0 154 0.033708 0.022472 0.006849 0.016854 0.005618 0 178 0.035242 0.048458 0.006849 0.630542 0.005464 0 227 0.137931 0.672414 0.034483 0 0 0 58 0.094527 0.034826 0.020548 0.004975 0.016393 0 201 0.01087 0 0 0 0.021739 0 92 0.021583 0.007194 0 0.014388 0.748201 0 139 0.040107 0.062745 0.006849 0 0.010929 0 374 0.195122 0 0.02439 0.02439 0 0 41 0.110465 0.017442 0 0.011628 0 0 172 0.040816 0.510204 0.102041 0.020408 0 0 49 0 0 0.837838 0 0 0 111 0.075949 0.253165 0 0 0.278481 0 79 0.16 0 0 0 0 0 25 0.119048 0.011905 0 0 0.035714 0.0625 84 0.035714 0.035714 0 0 0 0.8125 28 0 0 0 0 0 0 10 0 0 0 0 0 0 10 0 0 0 0 0 0 9 0.030769 0 0 0 0 0 65 0 0 0 0 0 0 21 0.142857 0 0 0 0 0 7 382 255 146 203 183 16
Table S3. Functional enrichment of modules identified in filtered-hc and updated-hc http://bionas.usc.edu/pdhub/table_s3.xls Functional enrichment of modules identified in Filtered-HC 1 2 3 4 5 6 amino acid and derivative metabolism 0.265986 1 0.113539 1 1 0.391256 biological_process unknown 0.636723 0.102139 0.998215 0.966742 1 0.022975 carbohydrate metabolism 0.589185 1 0.220435 1 1 0.124732 cell-wall-and-membrane organization and biogenesis 0.248599 0.307357 1 1 1 3.31E-05 cell budding and cytokinesis 1 0.916713 1 0.983561 1 1.72E-10 cell cycle 0.749702 0.979191 0.999334 0.999566 1 0.996938 cell homeostasis 0.138066 1 0.029449 1 0.321687 1 cellular respiration 0.013892 0.174546 1 1 1 1 conjugation 1 1 0.906121 0.854526 1 0.942358 cytoskeleton organization and biogenesis 1 0.732089 1 0.999929 0.863566 0.000186 DNA metabolism 0.982286 0.992462 0.39298 0.003225 0.000928 0.888746 generation of precursor metabolites and energy 0.487226 1 1 1 1 0.002047 lipid metabolism 0.623996 0.410411 0.844518 1 1 0.057509 meiosis 0.014561 0.990401 0.936821 0.471186 0.116345 0.926317 morphogenesis 0.359661 0.479993 0.193567 1 1 0.640537 nuclear organization and biogenesis 1 5.87E-22 1 1 1 0.971602 organelle organization and biogenesis 1 0.990992 0.997776 0.998661 0.000735 4.72E-09 protein biosynthesis and catabolism 0.999702 0.908631 1 0.039489 0.991075 0.98849 protein modification 0.014561 0.578598 0.30618 0.995844 0.974699 0.260623 pseudohyphal growth 0.041352 0.858195 1 1 1 1 response to stress 0.060365 0.029762 0.627375 0.999304 0.599575 0.001682 ribosome biogenesis and assembly 0.993358 0.99462 0.995851 1.09E-48 0.562451 1 RNA metabolism 0.020292 0.411452 0.996575 1.02E-11 0.00014 0.999903 signal transduction 0.903772 0.967739 0.066091 1 1 0.995355 sporulation 0.606979 1 1 0.926143 1 0.61937 transcription 0.026236 0.987106 1.89E-47 1 0.92012 1 transport 0.998269 0.005734 1 1 0.930744 0.973204 vitamin metabolism 1 1 1 0.000123 1 1
7 8 9 10 11 12 13 14 15 0.222788 0.760226 0.166372 1 0.816515 1 0.320217 1 0.21467 0.978371 0.799874 0.000102 0.778744 0.742973 0.954356 0.224146 0.899355 0.08018 0.000887 0.342893 0.863579 1 1 1 0.639855 0.515241 1 1 0.971967 0.02395 0.104161 0.985648 1 0.947018 1 1 1 0.980534 0.161369 1 0.483705 0.388423 0.005029 1 1 0.007099 0.923517 1.10E-15 0.194771 0.999787 0.699676 0.931137 0.243923 1 1 1 0.086661 1 0.669702 1 1 1 1 0.376094 1 0.88389 1 1 1 1 0.352866 1 1 0.510248 2.01E-07 1 0.872802 0.446155 1 0.264118 1 1 1 0.001525 0.77628 0.811881 0.08518 1 1 0.052049 0.999698 1.68E-07 0.999699 0.981954 1 1 0.999974 3.48E-23 1 0.018906 1 0.732761 1 1 0.271965 0.535483 1 1 1 0.744941 0.141728 0.347726 0.471688 1 0.674663 1 0.206414 1 0.93417 0.077525 1 1 0.445511 1 0.001298 0.527073 1 1 0.219429 1 1 1 1 1 0.004855 1 0.885542 0.703045 1 1 1 1 0.717241 1 0.941172 0.453076 0.995116 1 0.00221 0.782617 0.974926 0.734753 1 1.19E-15 0.9991 0.999995 0.305329 0.999979 7.63E-11 0.999086 1 1 0.810982 1.86E-06 0.621058 0.000942 0.896065 0.198996 1 1 1 0.691145 0.84431 1.62E-09 0.441048 1 1 1 1 0.040465 0.035643 0.953561 0.427718 0.020602 0.92407 1 0.981386 0.940689 1 0.98802 1 1 1 0.997694 0.907769 0.513361 1 0.694424 1 0.999998 1 1 1 0.988036 6.79E-34 1 1 1 0.961982 2.37E-09 0.084976 1 1 0.931941 1 3.19E-05 0.046368 0.728675 0.46263 1 0.787507 1 1 0.532403 1 0.757035 2.86E-09 0.999981 1 1 1 0.999984 0.895927 0.671201 0.998672 0.999965 0.999928 0.126338 6.04E-46 0.845809 0.999584 0.999953 0.944846 1 1 0.659756 1 1 1 1 1 1
16 17 18 19 20 21 22 23 0.560546 1 1 1 1 1 1 1 0.894895 0.841894 1 1 1 0.627522 0.740864 0.34842 0.511019 1 1 1 1 1 1 1 0.055787 1 1 1 1 0.027985 1 1 0.660753 1 1 1 1 1 1 1 0.236037 0.06569 1 1 0.558912 1 1 1 0.096951 1 1 1 1 1 1 1 0.349484 1 1 1 1 0.004549 1 1 0.632086 1 1 1 1 1 1 1 1.93E-07 0.258006 1 1 1 1 1 1 0.994937 0.926454 1 1 0.771225 0.997644 1 0.137346 1 1 1 1 1 0.355837 1 1 0.544628 1 1 1 1 1 1 1 0.466944 0.593234 0.280011 1 0.000268 1 0.482396 0.188511 1 1 1 1 1 1 1 1 0.350862 1 1 1 1 1 1 1 0.046704 1 1 1 1 0.879304 1 1 0.959205 2.11E-05 1 1 1 5.55E-16 0.815174 1 0.96283 0.543149 1 1 0.005768 1 1 1 1 1 1 1 1 1 1 1 0.938648 0.626766 1 1 1 1 1 1 1 1 1 1.60E-06 1 1 1 1 0.99944 1 1 0.000215 1 1 1 1 0.559414 1 1 1 1 1 0.385329 1 0.000755 0.232914 1 1 1 1 0.176441 1 0.672546 0.934511 1 1 0.087554 1 1 0.14717 0.449052 0.694162 6.59E-05 1 1 0.004172 4.05E-07 1 1 1 1 1 1 1 1 1
Functional enrichment of modules identified in Updated-HC 1 2 3 4 5 6 amino acid and derivative metabolism 0.9725269 0.0791247 0.0117489 0.9893175 1 0.2474884 biological_process unknown 0.9991923 0.0003995 0.2520992 0.1172452 0.6999005 0.0080175 carbohydrate metabolism 1 0.2350137 0.0069339 0.9949465 0.2883697 0.0961804 cell-wall-and-membrane organization and biogenesis 0.6948344 0.0270818 0.1076053 0.0867831 0.7766817 0.0388601 cell budding and cytokinesis 0.0056115 0.0063943 0.2965493 0.9488957 0.6584536 0.7967687 cell cycle 3.83E-10 0.7333202 0.8525751 0.9503486 0.0058207 0.8750898 cell homeostasis 0.88491 0.496066 0.785196 0.2877057 0.0174355 0.5698923 cellular respiration 0.9919429 0.5000835 0.011189 0.267806 0.3667734 0.5232478 conjugation 0.068916 0.5209395 0.9317179 0.1454159 1 0.3572507 cytoskeleton organization and biogenesis 0.111735 1.20E-06 0.971257 0.4748636 0.2956422 0.5597414 DNA metabolism 0.9994219 0.9995501 0.9837408 0.0102698 0.9969481 0.9989068 generation of precursor metabolites and energy 1 0.0313187 0.0260292 0.9101073 0.7652294 0.0564826 lipid metabolism 0.995574 0.1969771 0.0063567 0.1868901 1 0.5520349 meiosis 0.2853918 0.9678156 0.239716 0.4427915 0.8056699 0.8851937 morphogenesis 0.1702734 0.1753959 1 0.6842943 0.3372243 0.1097757 nuclear organization and biogenesis 0.6024434 0.9316469 2.04E-14 0.9620251 1 0.6691052 organelle organization and biogenesis 0.1200396 0.0017562 0.245584 0.9187628 0.8638193 0.3288107 protein biosynthesis and catabolism 0.9999053 0.9933677 0.9565495 0.0059585 0.9927477 0.9937566 protein modification 0.0834216 0.7890158 0.2953802 0.8355096 0.0329292 0.0156513 pseudohyphal growth 3.63E-05 0.4320961 0.1969124 0.9652223 0.3328326 0.8728372 response to stress 0.3087146 0.0235435 0.866745 0.9818492 0.0973626 0.1051332 ribosome biogenesis and assembly 1 1 0.9994292 0.9998729 0.9836308 0.9999456 RNA metabolism 1 0.999992 0.9785921 0.9999799 0.0080137 0.9999998 signal transduction 1.46E-07 0.7808333 0.9750809 0.9299229 0.6198556 0.0076451 sporulation 0.9898195 0.9437261 0.5551168 0.6539708 0.1222445 0.4833414 transcription 0.99542 0.9998666 0.9974418 0.9642338 0.0315423 0.9703879 transport 3.70E-15 0.9071526 0.8238892 0.0006978 0.9998195 0.0752825 vitamin metabolism 0.9707836 0.2476924 0.0760463 0.7352597 1 1
7 8 9 10 11 12 13 14 0.5527457 0.0040447 0.9363311 0.9624917 0.5573237 0.9942314 0.7164466 1 0.9897923 0.9845049 0.0007848 0.7967575 0.9567416 0.9916552 0.9965355 0.8230296 0.0286702 0.5755296 0.0606399 0.9834161 0.904797 1 1 1 0.9706397 0.9845082 0.5153497 0.7284915 0.6859521 1 1 1 0.3008955 0.9981159 0.9937179 0.7113313 0.7701983 0.7171067 0.8721053 1 0.8481233 0.9996931 0.9924179 0.1165533 0.6954199 0.9997599 0.3927648 1 1 0.1284459 0.6049851 0.3593631 1 0.8905431 1 1 0.798105 0.128338 0.913994 0.7653625 0.4739808 1 1 1 1 0.7774546 0.9639398 0.1749761 1 0.6575767 0.4861176 1 0.4392344 0.9957735 0.4744981 0.9974966 0.9678276 0.9828842 0.932022 1 0.2111932 0.9849099 0.3698916 6.44E-09 0.9994762 0.9958998 6.22E-17 0.6927239 0.8336984 0.9820932 0.4571164 0.0322386 1 1 1 1 1 1 0.1714066 0.0289 0.7198 0.9362486 0.961105 1 0.3185985 0.3012837 0.0835553 0.3189439 1 0.9987037 0.2022294 0.3619441 1 0.300435 1 1 1 1 1 1 1 0.8288272 1 1 1 1 1 1 0.9295789 0.8377543 0.9952762 0.3301444 0.9312588 0.9447339 0.4725191 1 3.71E-15 0.9823103 0.2809886 0.0208198 0.2324721 0.8005862 0.9858509 1.11E-06 0.8944585 0.7508026 0.6066057 0.9998879 0.999638 0.9999991 2.76E-06 1 1 0.9640841 0.5027312 1 1 0.9275538 0.8511699 1 0.0012712 0.2477206 0.4153699 0.9997753 0.9529279 0.9902142 0.9978591 1 0.8824434 0.5577316 0.9989653 0.6541259 0.4039159 1.16E-63 0.9890039 1 0.948385 0.9221233 0.9971529 0.2882379 6.80E-38 1.12E-21 0.9999768 1 1 0.6730646 0.4676457 0.941257 1 0.9900513 1 1 0.0168782 0.6476378 0.1687452 0.9308872 1 0.7447322 0.3001559 0.1664058 0.9859152 1.17E-35 0.9829652 0.9975202 0.9992908 0.9999544 2.51E-06 0.6803181 0.9997146 0.9981452 0.1671754 0.7441193 0.9997383 0.9999857 0.9990078 1 1 0.037078 0.1571794 0.6012976 1 0.6056489 1 1
Table S4.Functional enrichment of modules identified in Human interactome. Only the modules containing more than 40 genes were listed. http://bionas.usc.edu/pdhub/table_s4.xls Table S5. Details of the node role assignment, module classification and function annotation http://bionas.usc.edu/pdhub/table_s5.xls