Benchmarking imputation methods for network inference using a novel method of synthetic scRNA-seq data generation

Abstract

Background: Single cell RNA-sequencing (scRNA-seq) has very rapidly become the new workhorse of modern biology providing an unprecedented global view on cellular diversity and heterogeneity. In particular, the structure of gene-gene expression correlation contains information on the underlying gene regulatory networks. However, interpretation of scRNA-seq data is challenging due to specific experimental error and biases that are unique to this kind of data including drop-out (or technical zeros). Methods: To deal with this problem several methods for imputation of zeros for scRNA-seq have been developed. However, it is not clear how these processing steps affect inference of genetic networks from single cell data. Here, we introduce Biomodelling.jl, a tool for generation of synthetic scRNA-seq data using multiscale modelling of stochastic gene regulatory networks in growing and dividing cells. Results: Our tool produces realistic transcription data with a known ground truth network topology that can be used to benchmark different approaches for gene regulatory network inference. Using this tool we investigate the impact of different imputation methods on the performance of several network inference algorithms. Conclusions: Biomodelling.jl provides a versatile and useful tool for future development and benchmarking of network inference approaches using scRNA-seq data.