PMC

Act5c-Gal4/TM6b female flies are crossed with males carrying UAS-X either balanced or not. The progeny is either wild-type or TM6b (Tubby larvae and pupae, Humerals adults). Phenotypes are counted and impact of different Toll pathway modifications is assessed by comparison with UAS-LacZ for overexpression constructs or with UAS-Cg1315 for RNAi constructs (A). Viability assay in larvae. Overexpression of Pelle is lethal, whereas Cactus and Toll-7 OE is partially lethal. No effect on viability is obtained with other modifications (B–B’). Viability assay in pupae. Pelle OE is lethal; overexpression of Cactus, Toll-7 and Toll-2 is partially lethal. Knock-down of Cactus, Dorsal, Dif and Toll-3 RNAi is partially lethal. No effect is obtained with Toll-9 OE (C–C’). Viability assay in adults. Overexpression of Pelle, Toll-2 and Tollo is lethal. Knock-down of Dorsal is lethal. Partial lethality is obtained by overexpressing Cactus, Toll-7, Dorsal and Dif or by knocking-down Cactus, Dif and Toll-3. No effect is observed when Toll-9 is either overexpressed or down-regulated (D–D’). ***P<0.001, **P<0.01, chi-square test.

(A) Study design for synthetic lethality analysis. (B) Single lethal reactions, lethal reaction pairs, and related pathways. Blue circle plot shows numbers of single lethal reactions (Single), lethal reaction pairs (Pairs) and all reactions in the model (All). Chart bar of single lethal reactions shows numbers of involved reactions in each pathway. Chart bar of reactions in lethal pairs shows numbers of individual reactions in each pathway. (C) Single lethal exchange/transport reactions, exchange/transport reactions in lethal reaction pairs and related metabolites. Brown circle plot shows numbers of single lethal exchange/transport reactions (Single), exchange/transport reactions in lethal reaction pairs (Pairs), and all exchange/transport reactions in the model (Exchange/Transport). Bar chart of single lethal reactions shows numbers of exchange/transport reactions and related metabolites. Bar chart of lethal reaction pairs shows numbers of individual exchange/transport reactions and related metabolites.

Single and double gene deletion predictions. The results of in silico gene deletion predictions are summarized. (A) Single gene deletion predictions are classified into four categories with respect to wild type: lethal (0%), growth reducing (>0% and <90%), growth reducing (>90% and <100%) and no effect (100%). For each case, the percentage of growth is indicated in the parentheses. (B) The lethal single gene deletions grouped according to metabolic processes. (C) The total number of lethal single and double gene deletions. Lethal double gene deletions can be classified as trivial lethal or non-trivial lethal. Trivial lethal implies that at least one of the genes involved is lethal in a single gene deletion. In non-trivial lethal double deletions, both genes involved are not lethal individually as single gene deletions but are lethal in combination.

(A) The two largest sub-networks that are specifically lethal to BUB1B^S cells are shown. The red, blue, and yellow represent BUB1B^S lethal genes, BUB1B^R lethal genes, and cancer lethal genes, respectively. (B) The significant pathways enriched for genes within sub-networks specific to BUB1B^S cells.