voom: precision weights unlock linear model analysis tools for RNA-seq read counts
Charity W. Law,Charity W. Law,Yunshun Chen,Yunshun Chen,Wei Shi,Wei Shi,Gordon K. Smyth,Gordon K. Smyth +7 more
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.read more
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Role of duplicate genes in determining the tissue-selectivity of hereditary diseases.
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mTORC1 activation in lung mesenchyme drives sex- and age-dependent pulmonary structure and function decline.
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TL;DR: This study identifies sex- and age-specific gene changes in the mTORC1-activated lung mesenchyme and establishes the importance of the WNT signaling pathway in the crosstalk between meschymal and epithelial subsets of cells observed in mesenchymal Tsc2-deficient lungs.
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Determining breast cancer histological grade from RNA-sequencing data
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Histone H3G34R mutation causes replication stress, homologous recombination defects and genomic instability in S. pombe
Rajesh K. Yadav,Carolyn M Jablonowski,Alfonso G Fernandez,Brandon R Lowe,Ryan A. Henry,David Finkelstein,Kevin J Barnum,Alison L. Pidoux,Yin-Ming Kuo,Jie Huang,Matthew J. O'Connell,Andrew J. Andrews,Arzu Onar-Thomas,Robin C. Allshire,Janet F. Partridge +14 more
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Sex-Specific Control of Human Heart Maturation by the Progesterone Receptor
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References
More filters
Journal ArticleDOI
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
Aravind Subramanian,Pablo Tamayo,Vamsi K. Mootha,Sayan Mukherjee,Benjamin L. Ebert,Michael A. Gillette,Amanda G. Paulovich,Scott L. Pomeroy,Todd R. Golub,Eric S. Lander,Jill P. Mesirov +10 more
TL;DR: The Gene Set Enrichment Analysis (GSEA) method as discussed by the authors focuses on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation.
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
Peter McCullagh,John A. Nelder +1 more
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,Wolfgang Huber +1 more
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.