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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Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets.
Ying-Bei Chen,Jianing Xu,Anders Jacobsen Skanderup,Anders Jacobsen Skanderup,Yiyu Dong,A. Rose Brannon,Lu Wang,Helen Won,Patricia Wang,Gouri Nanjangud,Achim A. Jungbluth,Wei Li,Virginia Ojeda,A. Ari Hakimi,Martin H. Voss,Nikolaus Schultz,Robert J. Motzer,Paul Russo,Emily H. Cheng,Filippo G. Giancotti,Filippo G. Giancotti,William Lee,Michael F. Berger,Satish K. Tickoo,Victor E. Reuter,James J. Hsieh,James J. Hsieh +26 more
TL;DR: Integrated analysis reveals a subset of 26% uRCC characterized by NF2 loss, dysregulated Hippo–YAP pathway and worse survival, whereas 21% URCC with mutations of MTOR, TSC1, T SC2 or PTEN and hyperactive mTORC1 signalling are associated with better clinical outcome.
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Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica
TL;DR: It is shown that lipid accumulation in Y. lipolytica at nitrogen limitation is similar to the overflow metabolism observed in many other microorganisms, e.g. ethanol production by Sacchromyces cerevisiae at nitrogen limitations.
Journal ArticleDOI
scVAE: variational auto-encoders for single-cell gene expression data.
Christopher Heje Grønbech,Christopher Heje Grønbech,Christopher Heje Grønbech,Maximillian Fornitz Vording,Pascal Timshel,Casper Kaae Sønderby,Tune H. Pers,Ole Winther,Ole Winther,Ole Winther +9 more
TL;DR: This work proposes a novel method based on variational auto-encoders (VAEs) for analysis of single-cell RNA sequencing (scRNA-seq) data that avoids data preprocessing by using raw count data as input and can robustly estimate the expected gene expression levels and a latent representation for each cell.
Journal ArticleDOI
Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros
Elizabeth Ng,Elizabeth Ng,Lisa Azzola,Freya Bruveris,Freya Bruveris,Vincenzo Calvanese,Belinda Phipson,Katerina Vlahos,Claire E Hirst,Vanta J. Jokubaitis,Qing C Yu,Jovana Maksimovic,Simone Liebscher,Vania Januar,Zhen Zhang,Brenda Williams,Brenda Williams,Aude Conscience,Jennifer Durnall,Steven Anthony Jackson,Magdaline Costa,David A. Elliott,David N. Haylock,David N. Haylock,Susan K. Nilsson,Susan K. Nilsson,Richard Saffery,Katja Schenke-Layland,Katja Schenke-Layland,Katja Schenke-Layland,Alicia Oshlack,Hanna K. A. Mikkola,Edouard G. Stanley,Edouard G. Stanley,Edouard G. Stanley,Andrew G. Elefanty,Andrew G. Elefanty,Andrew G. Elefanty +37 more
TL;DR: This work shows that simultaneous modulation of WNT and ACTIVIN signaling yields CD34+ hematopoietic cells with HOXA expression that more closely resembles that of cord blood in the aorta-gonad-mesonephros (AGM), and provides an approach to mimic in vitro a key early stage in human heMatopoiesis for the generation of AGM-derived hematoietIC lineages from hESCs.
Journal ArticleDOI
Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes
S. Alice Long,Jerill Thorpe,Hannah A. DeBerg,Vivian H. Gersuk,James A. Eddy,Kristina M. Harris,Mario R. Ehlers,Kevan C. Herold,Gerald T. Nepom,Peter S. Linsley +9 more
TL;DR: The findings identify and functionally characterize a partially exhausted cell type associated with response to teplizumab therapy and suggest that pathways regulating T cell exhaustion may play a role in successful immune interventions for T1D.
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