Figure 1.
The workflow of identifying cross-talk among risk pathways.
Step 1: Integration of genomic, DNA methylomic, and transcriptomic data for identification of candidate genes; Step 2: Identification of risk pathways by using candidate genes based on pathway enrichment analysis; Step 3: Identification of cross-talk among risk pathways by mapping candidate genes onto the human protein interaction network based on the random walk with restart method.
Figure 2.
Linkers and leaders in cross-talking pathways.
For cross-talking pathway pairs, the linker and leader genes show three situations. The black circles with different color represent the linker and/or leader genes with the alteration in different levels.
Figure 3.
Integrative information of candidate genes with alterations at multiple levels and risk pathways.
(A) Venn diagram showing the dysregulated groups between mRNA expression and another molecular level such as DNA methylation,DNA copy number and somatic mutation. (B) Comparisons among pathways enriched by potential candidate genes derived from different dysregulated groups. (C) The alteration patterns of candidate genes in at least two levels. (D) The significantly enriched risk pathways by candidate genes (FDR<0.05).
Figure 4.
The network of cross-talking pathways.
The cross-talking pathways with the alteration patterns of candidate genes in each risk pathway and linkers mediating cross-talk of pathway pairs are shown. Each square node represents the risk pathway and the circle made of linkers. The different colors of linkers represent the change in different molecular level.
Figure 5.
The architecture of cross-talking pathways.
The blue squares represent risk pathways in the network of cross-talking pathways and the lightly grey circles with different color asterisks represent the leaders with the alteration in different levels.
Figure 6.
Integrative pathways from different cross-talking pathway pairs.
(A) “Complement and coagulation cascades” and “Pathway in cancer_1”, “Hedgehog signaling pathway” and “Pathway in cancer_2”; (B) “Axon guidance” and “MAPK signaling pathway”. Each ellipse represents a gene in KEGG pathway or ppi network. For a given gene, the ellipse is divided into four parts (from left to right) corresponding to different molecular level with abnormal states (red) in mRNA expression, (green) DNA methylation, (yellow) copy number and blue (somatic mutation), respectively.