Non-parametric modelling of temporal and spatial counts data from RNA-seq experiments

A bstract

Motivation

The negative binomial distribution is a good model for counts data from both bulk and single-cell RNA-sequencing (RNA-seq). Gaussian process (GP) regression provides a useful non-parametric approach for modeling temporal or spatial changes in gene expression. However, currently available GP regression methods that implement negative binomial likelihood models do not scale to the increasingly large datasets being produced by single-cell and spatial transcriptomics.

Results

The GPcounts package implements GP regression methods for modelling counts data using negative binomial likelihood functions. Computational efficiency is achieved through the use of variational Bayesian inference. The GP function models changes in the mean of the negative binomial likelihood through a logarithmic link function and the dispersion parameter is fitted by maximum likelihood. We also provide the option of modelling additional dropout using a zero-inflated negative binomial likelihood. We validate the method on simulated time course data, showing that it is better able to identify changes in over-dispersed counts data than methods based on Gaussian or Poisson likelihoods. To demonstrate temporal inference, we apply GPcounts to single-cell RNA-seq datasets after pseudotime and branching inference. To demonstrate spatial inference, we apply GPcounts to data from the mouse olfactory bulb to identify spatially variable genes and compare to a published GP method with a Gaussian likelihood function. Our results show that GPcounts can be used to model temporal and spatial counts data in cases where simpler Gaussian and Poisson likelihoods are unrealistic.

Availability

GPcounts is implemented using the GPflow library in Python and is available at https://github.com/ManchesterBioinference/GPcounts along with the data, code and notebooks required to reproduce the results presented here.