Classification-based Inference of Dynamical Models of Gene Regulatory Networks

TLDR: This work presents FIGR (Fast Inference of Gene Regulation), a novel classification-based inference approach to determining gene circuit parameters that is faster than global non-linear optimization by nearly three orders of magnitude and its computational complexity scales much better with GRN size.

Abstract: Cell-fate decisions during development are controlled by densely interconnected gene regulatory networks (GRNs) consisting of many genes. Inferring and predictively modeling these GRNs is crucial for understanding development and other physiological processes. Gene circuits, coupled differential equations that represent gene product synthesis with a switch-like function, provide a biologically realistic framework for modeling the time evolution of gene expression. However, their use has been limited to smaller networks due to the computational expense of inferring model parameters from gene expression data using global non-linear optimization. Here we show that the switch-like nature of gene regulation can be exploited to break the gene circuit inference problem into two simpler optimization problems that are amenable to computationally efficient supervised learning techniques. We present FIGR (Fast Inference of Gene Regulation), a novel classification-based inference approach to determining gene circuit parameters. We demonstrate FIGR9s effectiveness on synthetic data as well as experimental data from the gap gene system of Drosophila. FIGR is faster than global non-linear optimization by nearly three orders of magnitude and its computational complexity scales much better with GRN size. On a practical level, FIGR can accurately infer the biologically realistic gap gene network in under a minute on desktop-class hardware instead of requiring hours of parallel computing. We anticipate that FIGR would enable the inference of much larger biologically realistic GRNs than was possible before. FIGR Source code is freely available at http://github.com/mlekkha/FIGR.