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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

Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

TL;DR: This work presents DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates, which enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression.
Journal ArticleDOI

limma powers differential expression analyses for RNA-sequencing and microarray studies

TL;DR: The philosophy and design of the limma package is reviewed, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
Posted ContentDOI

Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

TL;DR: This work presents DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates, which enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression.
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

Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial

TL;DR: Treatment with atezolizumab resulted in a significantly improved RECIST v1.1 response rate, compared with a historical control overall response rate of 10%, and Exploratory analyses showed The Cancer Genome Atlas (TCGA) subtypes and mutation load to be independently predictive for response to atezolediazepine.
References
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Book ChapterDOI

limma: Linear Models for Microarray Data

TL;DR: This chapter starts with the simplest replicated designs and progresses through experiments with two or more groups, direct designs, factorial designs and time course experiments with technical as well as biological replication.
Journal ArticleDOI

Landscape of transcription in human cells

Sarah Djebali, +87 more
- 06 Sep 2012 - 
TL;DR: Evidence that three-quarters of the human genome is capable of being transcribed is reported, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs that prompt a redefinition of the concept of a gene.
Journal ArticleDOI

Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation

TL;DR: A flexible statistical framework is developed for the analysis of read counts from RNA-Seq gene expression studies, and parallel computational approaches are developed to make non-linear model fitting faster and more reliable, making the application of GLMs to genomic data more convenient and practical.
Book

Bioinformatics and Computational Biology Solutions Using R and Bioconductor

TL;DR: In this article, the authors present a detailed case study of R algorithms with publicly available data, and a major section of the book is devoted to fully worked case studies, with a companion website where readers can reproduce every number, figure and table on their own computers.
Journal ArticleDOI

The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote

TL;DR: This article proposes an elegantly simple multi-seed strategy, called seed-and-vote, for mapping reads to a reference genome, which uses a relatively large number of short seeds extracted from each read and allows all the seeds to vote on the optimal location.
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