IQCELL: A platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data

The increasing availability of single-cell RNA-sequencing (scRNA-seq) data from various developmental systems provides the opportunity to infer gene regulatory networks (GRNs) directly from data. Herein we describe IQCELL, a platform to infer, simulate, and study executable logical GRNs directly from scRNA-seq data. Such executable GRNs allow simulation of fundamental hypotheses governing developmental programs and help accelerate the design of strategies to control stem cell fate. We first describe the architecture of IQCELL. Next, we apply IQCELL to scRNA-seq datasets from early mouse T-cell and red blood cell development, and show that the platform can infer overall over 74% of causal gene interactions previously reported from decades of research. We will also show that dynamic simulations of the generated GRN qualitatively recapitulate the effects of known gene perturbations. Finally, we implement an IQCELL gene selection pipeline that allows us to identify candidate genes, without prior knowledge. We demonstrate that GRN simulations based on the inferred set yield results similar to the original curated lists. In summary, the IQCELL platform offers a versatile tool to infer, simulate, and study executable GRNs in dynamic biological systems. Author summaryExecutable GRNs provide and important strategy to model complex intracellular dynamics in development and disease. Here we introduce IQCELL, a platform to infer, simulate, and study executable logical GRNs directly from single cell sequencing data. IQCELL is an integrative platform that includes modules for gene selection, building logical GRNs, and simulating developmental trajectories under normal and perturbed conditions. We demonstrate the utility of IQCELL by reconstructing GRNs for early mouse T-cell and red blood cell development. We show that IQCELL can "automatically" infer the vast majority of gene interactions previously reported from decades of experimental research. IQCELL also provides users with a platform to simulate the developmental trajectories of cells. We show that dynamic simulations of the inferred GRNs resemble experimentally observed gene expression dynamics and capture the effects of genetic perturbation studies. IQCELL offers a versatile tool to infer and simulate GRNs in dynamic biological systems.