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Open AccessJournal ArticleDOI

voom: precision weights unlock linear model analysis tools for RNA-seq read counts

TLDR
New normal linear modeling strategies are presented for analyzing read counts from RNA-seq experiments, and the voom method estimates the mean-variance relationship of the log-counts, generates a precision weight for each observation and enters these into the limma empirical Bayes analysis pipeline.
Abstract
New normal linear modeling strategies are presented for analyzing read counts from RNA-seq experiments. The voom method estimates the mean-variance relationship of the log-counts, generates a precision weight for each observation and enters these into the limma empirical Bayes analysis pipeline. This opens access for RNA-seq analysts to a large body of methodology developed for microarrays. Simulation studies show that voom performs as well or better than count-based RNA-seq methods even when the data are generated according to the assumptions of the earlier methods. Two case studies illustrate the use of linear modeling and gene set testing methods.

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Journal ArticleDOI

Gene expression variability and the analysis of large-scale RNA-seq studies with the MDSeq.

TL;DR: The analysis of gene expression variability with the MDSeq on the GTEx human brain tissue data has identified pathways associated with common neurodegenerative disorders when gene expression means were conserved.
Journal ArticleDOI

A nested parallel experiment demonstrates differences in intensity-dependence between RNA-seq and microarrays

TL;DR: Quantitative PCR validations which indicate that microarrays may demonstrate greater systematic bias in low-intensity genes than in RNA-seq are carried out, demonstrating that power and accuracy are more dependent on per-gene read depth inRNA-Seq than they are on fluorescence intensity in microarray.
Journal ArticleDOI

Administration of aerosolized SARS-CoV-2 to K18-hACE2 mice uncouples respiratory infection from fatal neuroinvasion

- 28 Jan 2022 - 
TL;DR: In this paper , the authors used an inhalation tower system that allows exposure of unanesthetized mice to aerosolized virus under controlled conditions, which resulted in robust viral replication in the respiratory tract, anosmia, and airway obstruction but did not lead to fatal viral neuroinvasion.
Posted ContentDOI

Alignment and mapping methodology influence transcript abundance estimation

TL;DR: The performance of lightweight mapping and alignment-based approaches varies significantly, both in terms of quantification and downstream differential expression analysis, and a new alignment methodology is introduced to overcome the shortcomings of lightweight approaches without incurring the computational cost of traditional alignment.
References
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Journal ArticleDOI

edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.

TL;DR: EdgeR as mentioned in this paper is a Bioconductor software package for examining differential expression of replicated count data, which uses an overdispersed Poisson model to account for both biological and technical variability and empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference.
Book

Generalized Linear Models

TL;DR: In this paper, a generalization of the analysis of variance is given for these models using log- likelihoods, illustrated by examples relating to four distributions; the Normal, Binomial (probit analysis, etc.), Poisson (contingency tables), and gamma (variance components).
Journal ArticleDOI

featureCounts: an efficient general-purpose program for assigning sequence reads to genomic features

TL;DR: FeatureCounts as discussed by the authors is a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments, which implements highly efficient chromosome hashing and feature blocking techniques.
Journal ArticleDOI

Differential expression analysis for sequence count data.

Simon Anders, +1 more
- 27 Oct 2010 - 
TL;DR: A method based on the negative binomial distribution, with variance and mean linked by local regression, is proposed and an implementation, DESeq, as an R/Bioconductor package is presented.
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