The Annals of Applied Statistics

Deconvolution of base pair level RNA-Seq read counts for quantification of transcript expression levels

Han Wu and Yu Zhu

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Abstract

RNA-Seq has emerged as the method of choice for profiling the transcriptomes of organisms. In particular, it aims to quantify the expression levels of transcripts using short nucleotide sequences or short reads generated from RNA-Seq experiments. In real experiments, the label of the transcript, from which each short read is generated, is missing, and short reads are mapped to the genome rather than the transcriptome. Therefore, the quantification of transcript expression levels is an indirect statistical inference problem.

In this article, we propose to use individual exonic base pairs as observation units and, further, to model nonzero as well as zero counts at all base pairs at both the transcript and gene levels. At the transcript level, two-component Poisson mixture distributions are postulated, which gives rise to the Convolution of Poisson mixture (CPM) distribution model at the gene level. The maximum likelihood estimation method equipped with the EM algorithm is used to estimate model parameters and quantify transcript expression levels. We refer to the proposed method as CPM-Seq. Both simulation studies and real data demonstrate the effectiveness of CPM-Seq, showing that CPM-Seq produces more accurate and consistent quantification results than Cufflinks.

Article information

Source
Ann. Appl. Stat., Volume 10, Number 3 (2016), 1195-1216.

Dates
Received: October 2013
Revised: October 2015
First available in Project Euclid: 28 September 2016

Permanent link to this document
https://projecteuclid.org/euclid.aoas/1475069605

Digital Object Identifier
doi:10.1214/16-AOAS906

Mathematical Reviews number (MathSciNet)
MR3553222

Zentralblatt MATH identifier
06775264

Keywords
RNA-Seq transcriptome profiling finite Poisson mixture model convolution

Citation

Wu, Han; Zhu, Yu. Deconvolution of base pair level RNA-Seq read counts for quantification of transcript expression levels. Ann. Appl. Stat. 10 (2016), no. 3, 1195--1216. doi:10.1214/16-AOAS906. https://projecteuclid.org/euclid.aoas/1475069605


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Supplemental materials

  • Supplementary document for deconvolution of base pair level RNA-Seq read counts for quantification of transcript expression levels. We provide a supplementary document to show the details of the Poisson mixture distribution, the conditional distribution of $y_{m}^{r}$, the distribution of the illustrative example, the composite likelihood function, the details of the EM algorithm, the quantification method, supporting figures for the illustrative example, quantification results for MCF7, and the supporting figure for Example 1.