Optimization of transcription factor genetic circuits

Transcription factors (TFs) affect the expression of mRNAs. In essence, the TFs form a large computation network that controls many aspects of cellular function. This article introduces a computational method to optimize TF networks. The method extends recent advances in artificial neural network optimization. In a simple example, computational optimization discovers a four-dimensional TF network that maintains a circadian rhythm over many days, successfully buffering strong stochastic perturbations in molecular dynamics and entraining to an external day-night signal that randomly turns on and off at intervals of several days. This work highlights the similar challenges in understanding how computational TF and neural networks gain information and improve performance, and in how large TF networks may acquire a tendency for genetic variation and disease.