Clustering the genes for biological processes revealed a prominent role for transporters and the fact that a substantial number of genes could not be integrated into a known biological process and hence are labelled as “unclassified”. When we investigated the known signalling pathways represented by the genes we found that no clustering occurred when using the PANTHER database. This suggested that the isolated factors define signalling pathways that are separate from the ones they engage in healthy cells. In fact, it is well known that apoptosis factors often have completely different functions in non-apoptotic cells. This finding indicates that during apoptosis the components of the apoptosis signalling pathways are recruited from a diverse set of signalling circuits that are unrelated to cell death. In an effort to connect the isolated genes and define signalling pathways, we used the Ingenuity Pathways Analysis and found that several isolates are linked through the TNF/NF-kB signalling pathway. This protein complex regulates both pro- and anti-apoptotic genes and is activated under cell stress conditions. Three target genes were found and Atp1a1 has been reported to signal via the inositol 1,4,5-trisphosphate receptor to activate NFkB. Our screen for apoptosis genes has revealed a host of novel factors that have previously not been implicated in cell death regulation. Since each isolate is capable to initiate a downstream signalling pathway that eventually converges on the activation of the pro-apoptotic caspase proteases, the complexity and the vast number of cellular nodes that can regulate apoptosis becomes apparent. While we have isolated a number of positive controls, most of the genes that are known to regulate apoptosis were so far not discovered by the screen. Hence, our screen can be regarded as a first step to cover the whole genome for apoptosis genes, which will yield a inventory of its signalling nodules and allow mapping the “functome” of apoptosis. The positive controls of known apoptosis genes represent less than 10% of the genes determined in this study with many apoptosis genes such as caspases still missing. How many genes in the genome are involved in apoptosis? If we take as reference a compilation of known apoptosis genes, which lists 110 genes in H. sapiens, and extrapolate our data on known apoptosis inducers to the complete genome, assuming that the percentage of so far MK-1775 undiscovered apoptosis inducers correlates with the percentage of positive controls from the screen, this would result in a total of more than 1,000 genes involved in apoptosis. This supports the hypothesis that many additional genes exist that impact on apoptosis. The smallest group in figure 2 subsumes those genes that can principally be regarded as signalling factors. The scarcity of such genes indicates that apoptosis signalling is performed via different routes compared with most other signalling pathways. The largest gene group from the screen comprises enzymes. All enzyme classes were represented among the isolates except lyases and isomerases.