Inferring gene expression models from snapshot RNA data

Abstract

1Gene networks, key toward understanding a cells regulatory response, underlie experimental observations of single cell transcriptional dynamics. While information on the gene network is encoded in RNA expression data, existing computational frameworks cannot currently infer gene networks from such data. Rather, gene networks--composed of gene states, their connectivities, and associated parameters--are currently deduced by pre-specifying gene state numbers and connectivity prior to learning associated rate parameters. As such, the correctness of gene networks cannot be independently assessed which can lead to strong biases. By contrast, here we propose a method to learn full distributions over gene states, state connectivities, and associated rate parameters, simultaneously and self-consistently from single molecule level RNA counts. Notably, our method propagates noise originating from fluctuating RNA counts over networks warranted by the data by treating networks themselves as random variables. We achieve this by operating within a Bayesian nonparametric paradigm. We demonstrate our method on the lacZ pathway in Escherichia coli cells, the STL1 pathway in Saccharomyces cerevisiae yeast cells, and verify its robustness on synthetic data.