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Figure 1.

Interaction strength and modular architecture in networks.

(a) The relationship between tie strength and community structure is well established in social networks. (b) DDIs and DLIs correspond to strong and weak interactions in PPI networks, respectively.

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Figure 2.

DDI and DLI-assigned human PPI network.

(a) Categorizing human PPIs as DDIs or DLIs. A part of the human PPI network is shown to visualize DDI/DLI-assigned network. (b) Quality assessment of linear motifs during classification process. (c) Comparison of DDIs and DLIs categorized using our method to reference sets. (d) Edge clustering coefficients of DDIs and DLIs in the human PPI network. Grey bars show the distribution of average edge clustering coefficients in 105 networks with randomly assigned DDIs and DLIs.

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Figure 3.

Enrichment of DLIs and DDIs in interactions between and within biological modules.

(a) Odd ratio in functional groups. (b) Two functional groups, ‘cell-cell adhesion’ and ‘leukocyte migration’ were shown. (c) Odd ratio in protein complexes. (d) Two protein complexes, ‘RNA polymerase II’ and ‘BRCA1-associated genome surveillance’ were shown. (e) Odd ratio in subcellular localizations. (f) Two subcellular localizations, ‘cytoplasm’ and ‘nucleus’, were shown.

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Figure 4.

Expansion of DLIs in metazoan PPI networks.

(a) The number of conserved DLIs and DDIs in eukaryotic species. Values for nine representative eukaryotic species are shown. (b) Average proportion of DLIs and DDIs in 45 nonmetazoan and 54 metazoan species.

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Figure 5.

The expansion of DLIs contributed to the increase in modularity of metazoan PPI networks.

(a) Topological modularity, MPPI, in nine representative eukaryotic species. (b) A schematic showing how increased complexity is associated with MPPI. (c) Network modularity (MDLI/DDI) in nine representative eukaryotic species. (d) A schematic showing how DLIs are associated with increased MDLI/DDI. (e) The evolution of ‘cell-cell adhesion’ and ‘leukocyte migration’ groups is shown as an example.

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Figure 6.

Employing DLI/DDI information to identify biological modules.

(a) DLI/DDI information improves the identification of biological modules. (b) Quality of modules identified using conventional PPI data vs. DLI/DDI data. Module quality reflects the similarity of biological annotations in protein pairs within modules. (c) A detail of the merge process for conventional PPI and DLI/DDI-identified modules. The two horizontal arrows represent the merge process for seven proteins associated with ‘Voltage-gated Na+/K+ channels’ and ‘Fcε signaling pathway’. Ordinal numbers of specific merge steps are shown.

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