Quantitative characterization of recombinase-based digitizer circuits enables predictable amplification of biological signals.

ABSTRACT: Many synthetic gene circuits are restricted to single-use applications or require iterative refinement for incorporation into complex systems. One example is the recombinase-based digitizer circuit, which has been used to improve weak or leaky biological signals. Here we present a workflow to quantitatively define digitizer performance and predict responses to different input signals. Using a combination of signal-to-noise ratio (SNR), area under a receiver operating characteristic curve (AUC), and fold change (FC), we evaluate three small-molecule inducible digitizer designs demonstrating FC up to 508x and SNR up to 3.77 dB. To study their behavior further and improve modularity, we develop a mixed phenotypic/mechanistic model capable of predicting digitizer configurations that amplify a

SUBMITTER: Kiwimagi KA 

PROVIDER: S-EPMC8282836 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature