Damage Survival Pathways Figure 3. Glutathione and TOR pathways utilized for MMS survival. CG numbers are given for each Drosophila pathway component, as well as the protein names or complex names for their human orthologues. Pathway entry points are noted with Roman numerals at the top, and end points are at the bottom. A key for the following symbols is provided. Symbols encircled with thick lines represent proteins that act together or in a complex, while symbols encircled with thin lines represent paralogues or proteins that may substitute for one another. Proteins found to affect MMS survival are noted as down (death) or up triangles (resistance). Statistically significant proteins are indicated with black triangles, while trend hits are indicated with grey triangles. Essential genes are noted with a thick bar and any with downwards or upwards pointing boxes were also validated as conferring death or resistance, respectively, to MMS upon knock-down. Shaded squares are proteins not found to be hits after validation, and open squares were not tested in our validation. Yeast orthologues previously found to be required for MMS survival [3] are noted with a dot under the symbol. (A) Glutathione (an expanded list of GST family members is given in Table S4) and (B) TOR. doi:10.1371/journal.pgen.1000527.g003 connectivity of the resultant enlarged network was significantly improved yet again (Figure 6D and Table S7; p#4.6E-52). Similar to the analysis of the 202 validated MMS screen hits, we also compared the connectivity of the subnetworks containing the essential genes or pathway hits with that of a randomly rewired network consisting of the same nodes. Although at a lower statistical significance, the same general trend was observed (Table S7). This more inclusive network allows a view of all interactions PLoS Genetics | www.plosgenetics.org 8 June 2009 | Volume 5 | Issue 6 | e1000527