Nonparametric expression analysis using inferential replicate counts.

Nucleic Acids Research
A. ZhuMichael I Love

Abstract

A primary challenge in the analysis of RNA-seq data is to identify differentially expressed genes or transcripts while controlling for technical biases. Ideally, a statistical testing procedure should incorporate the inherent uncertainty of the abundance estimates arising from the quantification step. Most popular methods for RNA-seq differential expression analysis fit a parametric model to the counts for each gene or transcript, and a subset of methods can incorporate uncertainty. Previous work has shown that nonparametric models for RNA-seq differential expression may have better control of the false discovery rate, and adapt well to new data types without requiring reformulation of a parametric model. Existing nonparametric models do not take into account inferential uncertainty, leading to an inflated false discovery rate, in particular at the transcript level. We propose a nonparametric model for differential expression analysis using inferential replicate counts, extending the existing SAMseq method to account for inferential uncertainty. We compare our method, Swish, with popular differential expression analysis methods. Swish has improved control of the false discovery rate, in particular for transcripts with high infe...Continue Reading

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Citations

Feb 26, 2020·PLoS Computational Biology·Michael I LoveRob Patro
Jan 21, 2021·Bioinformatics·Scott Van BurenMichael I Love
Mar 7, 2021·Animals : an Open Access Journal From MDPI·Alexander Burren, Constanze Pietsch
May 1, 2021·Genome Biology·Matthew ChungJulie C Dunning Hotopp
Jun 1, 2021·NAR Genomics and Bioinformatics·Daniel C Jones, Walter L Ruzzo

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Datasets Mentioned

BETA
GSE38805

Methods Mentioned

BETA
RNA-seq
BitSeq
scRNA-seq
dscRNA-seq
laser-capture microdissection

Software Mentioned

Fluidigm
matrixStats
tximport package
SAMseq With Inferential Samples Helps
tximport
sleuth
R package qvalue
Ensembl
Alevin
iCOBRA

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