Bridged pairs and shared edges between 2ROs in the apoptosis pathway. Graphed representation of a subnetwork of the human cancer signalling map (HCSM) focusing on the apoptosis pathway is shown. There are three pairs of 2ROs in the subnetwork: BCL2-like 1 (BCL2L1) and BCL2, cysteine-aspartic acid protease 3 (CASP3) and CASP7, and CASP8 and CASP10. Nodes are colour-coded as follows: yellow signifies nodes mapping to 2ROs and green and red signify nodes mapping to conserved incoming edges (CIEs) and conserved outgoing edges (COEs), respectively. The edges shown are regulatory edges with the directionality indicated by arrows. CIEs suggest a common conserved regulator, located upstream in terms of information flow. In contrast, COEs indicate evolutionary conservation of a common regulatory target, located downstream. CASP8 and CASP10 are initiator caspases which locate to the death-inducing signalling complex (DISC). CASP3 and CASP7 are executioner caspases functioning downstream of initiator caspases. IAPs are inhibitors of apoptosis. The relative balance of antiapoptotic BCL2 and BCL2L1 versus proapoptotic BCL2-associated agonist of cell death, BCL2-antagonist/killer 1, BCL2-associated X protein, BH3 interacting domain death agonist, BCL2-interacting mediator of cell death, Puma and Noxa determines the activity of the intrinsic pathway of apoptosis.