  Next-generation sequencing technologies provide a revolutionary tool for
generating gene expression data. Starting with a fixed RNA sample, they
construct a library of millions of differentially abundant short sequence tags
or "reads", which constitute a fundamentally discrete measure of the level of
gene expression. A common limitation in experiments using these technologies is
the low number or even absence of biological replicates, which complicates the
statistical analysis of digital gene expression data. Analysis of this type of
data has often been based on modified tests originally devised for analysing
microarrays; both these and even de novo methods for the analysis of RNA-seq
data are plagued by the common problem of low replication. We propose a novel,
non-parametric Bayesian approach for the analysis of digital gene expression
data. We begin with a hierarchical model for modelling over-dispersed count
data and a blocked Gibbs sampling algorithm for inferring the posterior
distribution of model parameters conditional on these counts. The algorithm
compensates for the problem of low numbers of biological replicates by
clustering together genes with tag counts that are likely sampled from a common
distribution and using this augmented sample for estimating the parameters of
this distribution. The number of clusters is not decided a priori, but it is
inferred along with the remaining model parameters. We demonstrate the ability
of this approach to model biological data with high fidelity by applying the
algorithm on a public dataset obtained from cancerous and non-cancerous neural
tissues.
