Brooks, S. R. | Search bioRxiv

bioRxiv2023

RichPathR: a gene set enrichment analysis and visualization tool

Gene set enrichment analysis (GSEA) is an important step for disease and drug discovery. Genomic, transcriptomics, proteomics and epigenetic analysis of tissue or cells generates gene lists that need to be further investigated in the known biological context. The advent of high-throughput technologies generates the vast number of gene lists that are up or down regulated together. One way of getting meaningful insights of the relationship of these genes is utilizing existing knowledge bases linking them with biological functions or phenotypes. Multiple public databases with annotated gene sets are available for GSEA, and enrichR is the most popular web application still requiring custom tools for large-scale mining. richPathR package is a collection of R functions that helps researchers carry out exploratory analysis and visualization of gene set enrichment using EnrichR. AvailabilityThe package, test data and additional figures can be downloaded from https://github.com/niams-bdmds/richPathR.git. Contactsunh1@nih.gov

bioinformatics↗

bioRxiv2021

Transcriptomic analysis of mdx mouse muscles reveals a signature of early human Duchenne muscular dystrophy

The mdx mouse (C57BL/10ScSn-DMDmdx/J) is the oldest model of Duchenne muscular dystrophy (DMD). Mdx remains popular and has not been replaced by newer mouse models, despite criticisms that mdx has a nearly normal lifespan and mild pathology while DMD remains a severe, fatal disease. At some point we noticed that the absence of mdx RNA-seq data limited our ability to assess the results of physiological work on the mouse model and to compare these results to human genetic data [1]. We carried out RNA-seq analysis of wild-type and mdx mice of 2 and 5 months of age, using three hindlimb muscles per mouse: the flexor digitorum brevis (FDB), the extensor digitorum longus (EDL) and the soleus (SOL), with a total of 55 samples. We then mined the data and found that each of the three muscles is a valid experimental model for DMD-related mouse work, even the FDB, despite a delayed pathology development. We also show that the mdx mouse muscles are enriched in metabolic, developmental, regenerational and structural pathways that have been found to be the "disease signature" of DMD in young and presymptomatic subjects [38, 39]. Additionally, we show that healthy human muscle fiber microtubules present the grid-like organization found in control rodents but perturbed in the mdx mouse. We conclude that the mdx mouse appropriately mimics the early stages of DMD, with its microtubule defects signaling fiber regeneration [35]. We hope that these results may contribute to a better understanding of the failure of regeneration as DMD progresses.

genetics↗