The murine transcriptome reveals global aging nodes with organ-specific phase and amplitude, bioRxiv, 2019-06-07

Aging is the single greatest cause of disease and death worldwide, and so understanding the associated processes could vastly improve quality of life. While the field has identified major categories of aging damage such as altered intercellular communication, loss of proteostasis, and eroded mitochondrial function1, these deleterious processes interact with extraordinary complexity within and between organs. Yet, a comprehensive analysis of aging dynamics organism-wide is lacking. Here we performed RNA-sequencing of 17 organs and plasma proteomics at 10 ages across the mouse lifespan. We uncover previously unknown linear and non-linear expression shifts during aging, which cluster in strikingly consistent trajectory groups with coherent biological functions, including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Remarkably, these gene sets are expressed similarly across tissues, differing merely in age of onset and amplitude. Especially pronounced is widespread immune cell activation, detectable first in white adipose depots in middle age. Single-cell RNA-sequencing confirms the accumulation of adipose T and B cells, including immunoglobulin J-expressing plasma cells, which also accrue concurrently across diverse organs. Finally, we show how expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to aging of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of aging, thereby providing a foundation to track systemic sources of declining health at old age.

biorxiv genomics 100-200-users 2019

3D RNA-seq - a powerful and flexible tool for rapid and accurate differential expression and alternative splicing analysis of RNA-seq data for biologists, bioRxiv, 2019-06-01

AbstractRNA-sequencing (RNA-seq) analysis of gene expression and alternative splicing should be routine and robust but is often a bottleneck for biologists because of different and complex analysis programs and reliance on skilled bioinformaticians to perform the analysis. To overcome these issues, we have developed the “3D RNA-seq” App, an R shiny App which provides an easy-to-use, flexible and powerful tool for the three-way differential analysis Differential Expression (DE), Differential Alternative Splicing (DAS) and Differential Transcript Usage (DTU) of RNA-seq data. The full analysis is extremely rapidand can be done within hours. The program integrates Limma, a state-of-the-art, highly rated differential expression analysis tool and adopts best practice for RNA-seq analysis. It runs the analysis through a user-friendly graphical interface, can handle complex experimental designs, allows user setting of statistical parameters, visualizes the results through graphics and tables, and generates publication quality figures such as heat-maps, expression profiles and GO enrichment plots. The utility of 3D RNA-seq is illustrated by analysis of Arabidopsis and mouse RNA-seq data. The program is designed to be run by biologists with minimal bioinformatics experience (or by bioinformaticians) allowing lab scientists to take control of the analysis of their RNA-seq data.

biorxiv bioinformatics 100-200-users 2019

 

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