FIGURE 2 

BL module: A network visualization of the top 25 scoring genes in BL. Transcription factors are shown as circles, whereas other proteins are shown as squares. Protein–protein interactions are also shown in beige, protein–DNA interactions are black with an arrowhead, and transcription factor-modulated interactions are shown in blue with a circular endpoint. Red/green indicates overexpression or underexpression (P<1e-8), respectively in BL versus GC cells. There are some notable characteristics of this figure. First, all 25 genes form a connected module, which would not occur by chance. Second, MYC appears to be a central regulator of this module, as a full 21 out of the 25 members are MYC targets. MYC also appears regulated by MYC-associated zinc-finger protein (MAZ), which is also not differentially expressed. Third, there are interesting sets of genes that emerge, such as SMAD1, which is known to be associated with some NHL, and members of the NFAT family, including NFATC3, NFATC4, and NFAT5 (these proteins are members of the Wnt-signaling pathway). There also appears to be a protein complex of COL1A2, COL6A1 COL6A2, and FN1, which are all upregulated (and members of the cell signaling and ECM–receptor interaction pathway). These module diagrams can serve as a useful platform for further hypothesis generation and biochemical investigation.