Thomas P. Wytock and Adilson E. Motter

PNAS 121 (11) e2312942121

The lack of genome-wide mathematical models for the gene regulatory network complicates the application of control theory to manipulate cell behavior in humans. We address this challenge by developing a transfer learning approach that leverages genome-wide transcriptomic profiles to characterize cell type attractors and perturbation responses. These responses are used to predict a combinatorial perturbation that minimizes the transcriptional difference between an initial and target cell type, bringing the regulatory network to the target cell type basin of attraction. We anticipate that this approach will enable the rapid identification of potential targets for treatment of complex diseases, while also providing insight into how the dynamics of gene regulatory networks affect phenotype.
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