Modelling RNA-Seq data with a zero-inflated mixture Poisson linear model.

ABSTRACT

RNA sequencing (RNA-Seq) has been frequently used in genomic studies and has generated a vast amount of data. The RNA-Seq data are composed of two parts (a) a sequence of nucleotides of the genome; and (b) a corresponding sequence of counts, standing for the number of short reads whose mapped positions start at each position of the genome. One common feature of these count data is that they are typically nonuniform; recent studies have revealed that the nonuniformity is partially owing to a systematic bias resulted from the sequencing preference. Existing works in the literature model the nonuniformity with a single component Poisson linear model that incorporates the effects of the sequencing preference. However, we observe consistently that the short reads mapped to a gene may have a mixture structure and can be zero-inflated. A single component model may not suffice to model the complexity of such data. In this paper, we propose a zero-inflated mixture Poisson linear model for the RNA-Seq count data and derive a fast expectation-maximisation-based algorithm for estimating the unknown parameters. Numerical studies are conducted to illustrate the effectiveness of our method.