Engineering an AI-based forward-reverse platform for the design of cross-ribosome binding sites of a transcription factor biosensor.

ABSTRACT

A cross-ribosome binding site (cRBS) adjusts the dynamic range of transcription factor-based biosensors (TFBs) by controlling protein expression and folding. The rational design of a cRBS with desired TFB dynamic range remains an important issue in TFB forward and reverse engineering. Here, we report a novel artificial intelligence (AI)-based forward-reverse engineering platform for TFB dynamic range prediction and de novo cRBS design with selected TFB dynamic ranges. The platform demonstrated superior in processing unbalanced minority-class datasets and was guided by sequence characteristics from trained cRBSs. The platform identified correlations between cRBSs and dynamic ranges to mimic bidirectional design between these factors based on Wasserstein generative adversarial network (GAN) with a gradient penalty (GP) (WGAN-GP) and balancing GAN with GP (BAGAN-GP). For forward and reverse engineering, the predictive accuracy was up to 98% and 82%, respectively. Collectively, we generated an AI-based method for the rational design of TFBs with desired dynamic ranges.