Supplementary Information

Network Analysis Reveals Functional Cross-links between Disease and Inflammation Genes

Yunpeng Zhang, Huihui Fan, Juan Xu, Yun Xiao, Yanjun Xu, Yixue Li, Xia Li

Inventory of Supplementary Information

1. Supplementary Figure 1

2. Supplementary Figure 2

3. Supplementary Figure 3

4. Supplementary Figure 4

5. Supplementary Figure 5

6. Supplementary Figure 6

7. Supplementary Figure 7

8.Supplementary Table 1

Supplementary Figure 1.

Supplementary Figure 1. Degree comparison between inflammation genes, disease genes, and non-disease genes in the human PPI network. Via mapping inflammation genes and disease genes onto the human PPI network, we could further compare the degree distribution between them using Wilcoxon's Rank-Sum Test. Inflammation genes and disease genes were defined in the main text, while non-disease genes are the remaining nodes in the human PPI after mapping both inflammation and disease genes. *** indicates that the comparison between inflammation genes with non-disease genes, and the comparison of disease genes with non-disease genes are significant (p=6.8293e-07 and p= 2.4687e-75, separately).

Supplementary Figure 2.

Supplementary Figure 2. Mean degree in comparison with random distribution. 1000 random DINs were generated via mapping inflammation genes and disease genes to the random PPI network. The real mean degree of the DIN is shown by a red downward arrow, which is significantly higher when comparing with the random mean degree distribution of 1000 random DINs.

Supplementary Figure 3.

Supplementary Figure 3. Mean clustering coefficient in comparison with random distribution. 1000 random DINs were generated via mapping inflammation genes and disease genes to the random PPI network. The real mean clustering coefficient of the DIN is shown by a red downward arrow, which is significantly higher when comparing with the random mean clustering coefficient distribution of 1000 random DINs.

Supplementary Figure 4.

Supplementary Figure 4. Mean topological coefficient in comparison with random distribution. 1000 random DINs were generated via mapping inflammation genes and disease genes to the random PPI network. The real mean topological coefficient of the DIN is shown by a red downward arrow, which is significantly higher when comparing with the random mean topological coefficient distribution of 1000 random DINs.

Supplementary Figure 5.

Supplementary Figure 5. Example gene module of disease pair of cardiovascular and metabolic. The subnetwork was generated by mapping disease genes of cardiovascular and metabolic to the human PPI network. Genes that belongs to both inflammation and disease genes are marked with black border.

Supplementary Figure 6.

Supplementary Figure 6. Example gene module of disease pair of cardiovascular and immune. The subnetwork was generated by mapping disease genes of cardiovascular and immune to the human PPI network. Genes that belongs to both inflammation and disease genes are marked with black border.

Supplementary Figure 7.

Supplementary Figure 7. Example gene module of disease pair of aging and cancer. The subnetwork was generated by mapping disease genes of aging and cancer to the human PPI network. Genes that belongs to both inflammation and disease genes are marked with black border.

Supplementary Table 1. rank of the sum of Intimacy for disease pairs

Disease_1 / Disease_2 / Intimacy_1 / Intimacy_2 / Sum of Intimacy
immune / infection / 0.549388 / 0.817886 / 1.367274
cardiovascular / metabolic / 0.672727 / 0.639988 / 1.312715
normal variation / metabolic / 0.878205 / 0.422304 / 1.300509
cardiovascular / immune / 0.658299 / 0.63107 / 1.289369
aging / cancer / 0.853896 / 0.434055 / 1.287951
cardiovascular / hematological / 0.45699 / 0.816824 / 1.273814
aging / reproduction / 0.745671 / 0.519902 / 1.265573
cardiovascular / kidney / 0.462431 / 0.802083 / 1.264514
aging / immune / 0.837662 / 0.42156 / 1.259222
cancer / cardiovascular / 0.598671 / 0.632266 / 1.230937
cancer / metabolic / 0.612623 / 0.615188 / 1.227811
metabolic / reproduction / 0.477757 / 0.747059 / 1.224816
cancer / immune / 0.606499 / 0.610367 / 1.216866
kidney / metabolic / 0.77753 / 0.431577 / 1.209107
cancer / infection / 0.497111 / 0.707317 / 1.204428
hematological / reproduction / 0.653302 / 0.52902 / 1.182322
immune / metabolic / 0.590459 / 0.588909 / 1.179368
immune / kidney / 0.431621 / 0.747321 / 1.178942
metabolic / neurological / 0.562877 / 0.614864 / 1.177741
hematological / immune / 0.727201 / 0.425352 / 1.152553
hematological / metabolic / 0.73978 / 0.412186 / 1.151966
aging / infection / 0.6829 / 0.466504 / 1.149404
cancer / kidney / 0.424148 / 0.720238 / 1.144386
neurological / reproduction / 0.477724 / 0.665196 / 1.14292
infection / metabolic / 0.666423 / 0.465958 / 1.132381
normal variation / cancer / 0.732265 / 0.396245 / 1.12851
infection / kidney / 0.501545 / 0.625 / 1.126545
cardiovascular / vision / 0.444594 / 0.678267 / 1.122861
Psychological / metabolic / 0.595051 / 0.52406 / 1.119111
immune / vision / 0.430612 / 0.680667 / 1.111279
infection / neurological / 0.625772 / 0.482171 / 1.107943
kidney / pharmacogenomic / 0.619048 / 0.486099 / 1.105147
aging / kidney / 0.598485 / 0.504762 / 1.103247
metabolic / vision / 0.426543 / 0.670933 / 1.097476
kidney / neurological / 0.665179 / 0.424599 / 1.089778
kidney / reproduction / 0.589286 / 0.489314 / 1.0786
hematological / kidney / 0.545597 / 0.531101 / 1.076698
hematological / neurological / 0.661164 / 0.415064 / 1.076228
cancer / vision / 0.431542 / 0.6436 / 1.075142
aging / hematological / 0.555628 / 0.499528 / 1.055156
reproduction / vision / 0.501765 / 0.551467 / 1.053232
neurological / vision / 0.429006 / 0.622 / 1.051006
aging / vision / 0.56645 / 0.455067 / 1.021517
kidney / vision / 0.533333 / 0.484267 / 1.0176
pharmacogenomic / vision / 0.472999 / 0.542933 / 1.015932
normal variation / reproduction / 0.574573 / 0.435098 / 1.009671
hematological / vision / 0.527044 / 0.468267 / 0.995311
normal variation / kidney / 0.526709 / 0.450446 / 0.977155
Psychological / kidney / 0.404695 / 0.55506 / 0.959755
infection / vision / 0.455772 / 0.500667 / 0.956439
normal variation / vision / 0.524359 / 0.428267 / 0.952626
Psychological / vision / 0.40843 / 0.524133 / 0.932563
chemdependency / aging / 0.41292 / 0.49026 / 0.90318
normal variation / developmental / 0.471795 / 0.409592 / 0.881387
developmental / vision / 0.43729 / 0.4224 / 0.85969
chemdependency / vision / 0.414083 / 0.406 / 0.820083
neurological / pharmacogenomic / 0.527003 / 0.664265 / 1.191268
normal variation / hematological / 0.446581 / 0.425314 / 0.871895
chemdependency / kidney / 0.40155 / 0.415923 / 0.817473
normal variation / cardiovascular / 0.818376 / 0.419766 / 1.238142
normal variation / aging / 0.50406 / 0.507576 / 1.011636
developmental / kidney / 0.414988 / 0.439732 / 0.85472
chemdependency / infection / 0.42584 / 0.390325 / 0.816165
normal variation / immune / 0.74359 / 0.392508 / 1.136098
metabolic / pharmacogenomic / 0.511984 / 0.714702 / 1.226686
chemdependency / neurological / 0.721835 / 0.466987 / 1.188822
developmental / cardiovascular / 0.594724 / 0.419353 / 1.014077
Psychological / aging / 0.411978 / 0.677489 / 1.089467
chemdependency / metabolic / 0.638889 / 0.40955 / 1.048439
Psychological / cancer / 0.545658 / 0.491883 / 1.037541
developmental / infection / 0.443765 / 0.403577 / 0.847342
chemdependency / immune / 0.537468 / 0.382844 / 0.920312
chemdependency / reproduction / 0.465633 / 0.43549 / 0.901123
Psychological / immune / 0.555115 / 0.497584 / 1.052699
hematological / infection / 0.629717 / 0.490732 / 1.120449
normal variation / infection / 0.552137 / 0.415285 / 0.967422
cardiovascular / infection / 0.519904 / 0.74065 / 1.260554
Psychological / infection / 0.44223 / 0.523577 / 0.965807
chemdependency / cancer / 0.573643 / 0.399913 / 0.973556
Psychological / neurological / 0.637255 / 0.597556 / 1.234811
aging / pharmacogenomic / 0.725108 / 0.472198 / 1.197306
cancer / neurological / 0.536713 / 0.571074 / 1.107787
aging / cardiovascular / 0.865801 / 0.432025 / 1.297826
immune / pharmacogenomic / 0.492355 / 0.663755 / 1.15611
infection / pharmacogenomic / 0.546098 / 0.520306 / 1.066404
cardiovascular / reproduction / 0.505165 / 0.745 / 1.250165
cancer / pharmacogenomic / 0.534315 / 0.732314 / 1.266629
immune / reproduction / 0.473945 / 0.70951 / 1.183455
cancer / hematological / 0.425592 / 0.742138 / 1.16773
cardiovascular / neurological / 0.600034 / 0.619471 / 1.219505
normal variation / chemdependency / 0.46453 / 0.40814 / 0.87267
aging / neurological / 0.861472 / 0.444992 / 1.306464
immune / neurological / 0.556728 / 0.592989 / 1.149717
infection / reproduction / 0.567154 / 0.598137 / 1.165291
Psychological / chemdependency / 0.50789 / 0.76124 / 1.26913
normal variation / neurological / 0.688462 / 0.401843 / 1.090305
aging / metabolic / 0.883117 / 0.423075 / 1.306192
chemdependency / developmental / 0.430491 / 0.426379 / 0.85687
Psychological / cardiovascular / 0.576144 / 0.52624 / 1.102384
hematological / pharmacogenomic / 0.647013 / 0.473872 / 1.120885
chemdependency / cardiovascular / 0.58553 / 0.404098 / 0.989628
Psychological / pharmacogenomic / 0.519401 / 0.604949 / 1.12435
chemdependency / pharmacogenomic / 0.59199 / 0.48246 / 1.07445
Psychological / developmental / 0.406843 / 0.521823 / 0.928666
Psychological / reproduction / 0.44928 / 0.57598 / 1.02526
developmental / hematological / 0.396882 / 0.432704 / 0.829586
developmental / aging / 0.427818 / 0.496104 / 0.923922
developmental / immune / 0.582734 / 0.402263 / 0.984997
chemdependency / hematological / 0.413566 / 0.447642 / 0.861208
Psychological / hematological / 0.384667 / 0.551101 / 0.935768
cardiovascular / pharmacogenomic / 0.541942 / 0.720524 / 1.262466
pharmacogenomic / reproduction / 0.557424 / 0.631275 / 1.188699
cancer / reproduction / 0.488359 / 0.768824 / 1.257183
developmental / neurological / 0.528058 / 0.395954 / 0.924012
developmental / metabolic / 0.670264 / 0.426217 / 1.096481
developmental / reproduction / 0.51211 / 0.482549 / 0.994659
developmental / pharmacogenomic / 0.509832 / 0.441485 / 0.951317
Psychological / normal variation / 0.401381 / 0.663462 / 1.064843
developmental / cancer / 0.655276 / 0.4329 / 1.088176
normal variation / pharmacogenomic / 0.637821 / 0.4377 / 1.075521