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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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Journal ArticleDOI

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TL;DR: In this article, the authors consider a linear model with normally distributed but heteroscedastic errors and show that likelihood is more sensitive to small misspecifications in the functional relationship between the error variances and the regression parameter.
Journal ArticleDOI

Transcriptome of embryonic and neonatal mouse cortex by high-throughput RNA sequencing

TL;DR: The transcriptome analysis may serve as a blueprint for gene expression pattern and provide functional clues of previously unknown genes and disease-related genes during early brain development.
Journal ArticleDOI

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TL;DR: A normalization method is outlined for use when the assumptions of lowess normalization fail, which can occur when specialized boutique arrays are constructed that contain a subset of genes selected to test particular biological functions.
Book ChapterDOI

Score Tests in GLIM with Applications

TL;DR: The most common method of hypothesis testing in GLIM is the likelihood ratio method, however, in certain biostatistical application areas, score tests are more commonly used.
Journal ArticleDOI

A flexible count data model to fit the wide diversity of expression profiles arising from extensively replicated RNA-seq experiments

TL;DR: RNA-seq data with many replicates leads to a handful of count data distributions which can be accurately estimated with the statistical model illustrated in this paper, and a software package for R called tweeDEseq implementing a new test for differential expression based on the Poisson-Tweedie family is provided.
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