OBM Genetics 2020; 4(2), doi:10.21926/obm.genet.2002107

S1. Network Simulation using Human PPIs from the HPRD Database

We first selected hub genes from the HPRD PPI database (v9), with genes functioning at different cell layers (as summarized in Table S1). Simulated networks as discussed below were available at https://sourceforge.net/projects/msignet/.

Table S1 Selected hub genes from the HPRD PPI database.

Hub genes FYNEGFR

GRB2 MAPK AR SRC CDK1 ESR1 TP53 BRCA1

Number of nodes

61 74 70 62 68 85 37 74 88 51

Number of edges 321 411 523 292 368 541 100 507 417 255Cell layer Membrane Cytoplasm Nuclease

Network 1

We selected hub genes FYN, EGFR, MAPK, TP53, ESR1, CDK1 and BRCA1 to simulate the first network, in which we assigned genes interacting with FYN or ESR1 with a DE (differentially expressed) state and the other genes with an EE (equally expressed) state. There were 127 DE nodes and 927 DE-DE edges, totally 260 genes and 1663 edges in the network, with several EE modules with dense edge connections around, as shown in Figure S1.

Figure S1 Simulated Network #1 topology. We labeled DE genes with ‘red’ color and EE genes with ‘gray’ color.

Network 2

We selected hub genes EGFR, MAPK and TP53 to simulate a second network, where we assigned neighbor genes of EGFR or TP53 with a DE state and genes interacting with MARK with an EE states (including those also interacting with EGFR and TP53). There were 125 DE genes and 360

Page 1/2

OBM Genetics 2020; 4(2), doi:10.21926/obm.genet.2002107

DE-DE edges, totally 187 genes and 1010 edges, with two DE modules bridged by one EE module, as shown in Figure S2.

Figure S2 Simulated Network #2 topology. We labeled DE genes with ‘red’ color and EE genes with ‘gray’ color.

Network 3

In this case, we used the original PPI network including all genes within two jumps neighborhood around gene ESR1 and then selected DE genes if they interacted with FYN, EGFR ESR1, TP53, BRCA1, JUN or EP300 (Figure S3). All the other genes in the PPI network were EE genes (not shown here). In total, there were 220 DE genes with 1,513 edges between them, out of 2518 genes and 15,266 edges of the whole PPI network.

Figure S3 Simulated Network #3 topology. We only labeled DE genes with ‘red’ color.

Page 2/2