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

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TLDR
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.
Abstract
In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html .

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Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies

TL;DR: Heterochromatin decondensation, piwi and piRNA depletion and consequent transposable element dysregulation are identified as a pharmacologically targetable, mechanistic driver of neurodegeneration in tauopathy.
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A taxonomic signature of obesity in a large study of American adults

TL;DR: A strong and consistent taxonomic signature of obesity is identified and identification of microbes associated with obesity can potentially provide targets for obesity prevention and treatment.
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Neuroinflammatory astrocyte subtypes in the mouse brain.

TL;DR: In this paper, the authors investigated transcriptome changes of mouse cortical astrocytes after an acute inflammatory stimulus using the bacterial cell wall endotoxin lipopolysaccharide and identified fast transcriptomic changes occurring within hours that drastically change over time.
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Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2.

TL;DR: This study develops a feeder-free, long-term three-dimensional culture technique for hAT2 cells derived from primary human lung tissue, and investigates infection response to SARS-CoV-2, revealing rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hat2 cells, indicating robust endogenous innate immune response.
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FTO controls reversible m6Am RNA methylation during snRNA biogenesis.

TL;DR: The data reveal that FTO controls a previously unknown central step of snRNA processing involving reversible methylation, and suggest that epitranscriptomic information in snRNA may influence mRNA splicing.
References
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Journal ArticleDOI

Controlling the false discovery rate: a practical and powerful approach to multiple testing

TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
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.
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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).
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The Elements of Statistical Learning: Data Mining, Inference, and Prediction

TL;DR: In this paper, the authors describe the important ideas in these areas in a common conceptual framework, and the emphasis is on concepts rather than mathematics, with a liberal use of color graphics.
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