Motivation: Transcription in single cells is an inherently stochastic process as mRNA levels vary greatly between cells, even for genetically identical cells under the same experimental and environmental conditions. We present a stochastic two-state switch model for the population of mRNA molecules in single cells where genes stochastically alternate between a more active ON state and a less active OFF state. We prove that the stationary solution of such a model can be written as a mixture of a Poisson and a Poisson-beta probability distribution. This finding facilitates inference for single cell expression data, observed at a single time point, from flow cytometry experiments such as FACS or fluorescence in situ hybridization (FISH) as it allows one to sample directly from the equilibrium distribution of the mRNA population. We hence propose a Bayesian inferential methodology using a pseudo-marginal approach and a recent approximation to integrate over unobserved states associated with measurement error.
Results: We provide a general inferential framework which can be widely used to study transcription in single cells from the kind of data arising in flow cytometry experiments. The approach allows us to separate between the intrinsic stochasticity of the molecular dynamics and the measurement noise. The methodology is tested in simulation studies and results are obtained for experimental multiple single cell expression data from FISH flow cytometry experiments.
Availability and implementation: All analyses were implemented in R. Source code and the experimental data are available at https://github.com/SimoneTiberi/Bayesian-inference-on-stochastic-gene-transcription-from-flow-cytometry-data.
Supplementary information: Supplementary data are available at Bioinformatics online.