Fig. 1. Scheme for a multivariate linear combination in living cells.

(A) Two steps in the calculation of an intracellular miRNA profile. The left panel shows a canonical approach, such as high-throughput analysis, in which the detection of a large dataset for miRNA molecules in a cell is followed by multivariate statistics to recapitulate the profile with few parameters. The right panel shows our approach, in which the profile is recapitulated with an mRNA device before signal detection. (B) In our device, mRNA responds to multiple miRNAs independently and with high sensitivity to output the coded fluorescent protein (FL1 or FL2). The values of ρ denote miRNA activity that represses the reporter protein expression and are tuned by specific tuning factors, k. A linear combination of multiple miRNA activities in a cell is obtained as the ratio of two fluorescent reporters.