FIGURE 2. Operation of the molecular computer.

The complete sequences for all molecules shown are given in the Supplementary Methods. a, Part of the computation path for the diagnostic molecule for prostate cancer with all molecular indicators present, ending in drug release. The initial diagnostic molecule consists of a diagnosis moiety (grey) that encodes the left-hand side of the diagnostic rule (Fig. 1b) and a drug-administration moiety (light purple) incorporating an inactive drug loop (dark purple). At each computation step, the prevailing transition is shown, except for the processing of the symbol PIM1, for which details of the stochastic choice, accomplished by a regulated pair of competing transition molecules, are shown (dashed box, see c). b, Regulation of the two transitions for PIM1 by sub-sequences (tags) of overexpressed PIM1 mRNA, resulting in a relatively high level of the Yes ^PIM1Yes transition molecules and low level of the Yes ^PIM1No molecules. Each transition molecule contains regulation (green, orange) and computation (blue, grey) fragments. The 'inactivation tag' of PIM1 mRNA (light orange) displaces the 5' 3' strand of the transition molecule Yes ^PIM1No and destroys its computation fragment. The 'activation tag' of PIM1 mRNA (light green) activates the transition molecule Yes ^PIM1Yes. Initially, a protecting oligonucleotide (green) partially hybridizes to the 3' 5' strand of the transition molecule and blocks the correct annealing of its 5' 3' strand. The 'activation tag' displaces the protecting strand, allowing such annealing and rendering an active Yes ^PIM1Yes transition. Ideally, one PIM1 mRNA molecule inactivates one Yes ^PIM1No and activates one Yes ^PIM1Yes transition molecule. c, Stochastic processing of the symbol PIM1 by a regulated pair of competing transition molecules. The probability of a Yes Yes transition is high, resulting in a high level of diagnostic molecules in the state Yes and a low level in state No. d, Combining computation results for both types of diagnostic molecules, both with high Yes and low No final states, results in high release of drug and low release of drug suppressor, and hence in the administration of the drug.