Integration of AI and mechanistic modeling in generative adversarial networks for stochastic inverse problems

Stochastic inverse problems (SIP) address the behavior of a set of objects of the same kind but with variable properties, such as a population of cells. Using a population of mechanistic models from a single parametric family, SIP explains population variability by transferring real-world observations into the latent space of model parameters. Previous research in SIP focused on solving the parameter inference problem for a single population using Markov chain Monte Carlo methods. Here we extend SIP to address multiple related populations simultaneously. Specifically, we simulate control and treatment populations in experimental protocols by discovering two related latent spaces of model parameters. Instead of taking a Bayesian approach, our two-population SIP is reformulated as the constrained-optimization problem of finding distributions of model parameters. To minimize the divergence between distributions of experimental observations and model outputs, we developed novel deep learning models based on generative adversarial networks (GANs) which have the structure of our underlying constrained-optimization problem. The flexibility of GANs allowed us to build computationally scalable solutions and tackle complex model input parameter inference scenarios, which appear routinely in physics, biophysics, economics and other areas, and which can not be handled with existing methods. Specifically, we demonstrate two scenarios of parameter inference over a control population and a treatment population whose treatment either selectively affects only a subset of model parameters with some uncertainty or has a deterministic effect on all model parameters.