GSE124439
GSE GEO Potentially relatedPostmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia
Relations
Summary
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. While several pathogenic mutations have been identified, the vast majority of ALS cases have no family history of disease. Thus, for most ALS cases, the disease may be a product of multiple pathways contributing to varying degrees in each patient. Using machine learning algorithms, we stratified the transcriptomes of 148 ALS postmortem cortex samples into three distinct molecular subtypes. The largest cluster, identified in 61% of patient samples, displayed hallmarks of oxidative and proteotoxic stress. Another 19% of the samples showed predominant signatures of glial activation. Finally, a third group (20%) exhibited high levels of retrotransposon expression and signatures of TARDBP/TDP-43 dysfunction. We further demonstrated that TDP-43 (1) directly binds a subset of retrotransposon transcripts and contributes to their silencing in vitro, and (2) pathological TDP-43 aggregation correlates with retrotransposon de-silencing in vivo.
Overall Design
RNA-seq analysis of ALS patient samples and individuals without neurological disorders Contributor: NYGC ALS Consortium https://www.nygenome.org/research-areas/neurodegenerative-diseases/als-consortium/ Contributor: The Target ALS Human Postmortem Tissue Core http://www.targetals.org/
Analysis (2 steps)
View Data Processing- fastq Illumina RNASeq paired-end reads were aligned to the hg19 reference genome using STAR v2.5.2b with the following configurations: --outFilterMultimapNmax 100; --outFilterMismatchNoverReadLmax 0.04
- Genes and transposable elements (TE) were quantified using TEcount (from TEtranscripts v2.0.3) with the following configurations: hg19 genic GTF from refGene (Jan 2018), custom hg19 TE GTF generated from repeatMasker; --stranded reverse
Supplementary Files (1)
GEO Samples (176)
Dataset Citations (3)
Potentially Related Publications (1)
This accession was text-mined from the PMC full text of these publications. It may be referenced for comparison or reused from another study rather than generated for them.
Data Files (10)
| Accession | File Name | Stored Type | Output Type | Mapping Assembly | Size | Download | |
|---|---|---|---|---|---|---|---|
| — | CGND-HRA-00244_TGGTGGTA_ACC5G8ANXX_L001_001.R1.fastq.gz | RNA-Seq | 3.8 GB | link | |||
| — | CGND-HRA-00245_CCAGTTCA_ACBUUJANXX_L001_001.R1.fastq.gz | RNA-Seq | 6.5 GB | link | |||
| — | CGND-HRA-00246_GAGCTGAA_ACBUUJANXX_L002_001.R1.fastq.gz | RNA-Seq | 6.3 GB | link | |||
| — | CGND-HRA-00247_CACCTTAC_ACBRAPANXX_L004_001.R1.fastq.gz | RNA-Seq | 4.6 GB | link | |||
| — | CGND-HRA-00248_ACACAGAA_ACBUUJANXX_L002_001.R1.fastq.gz | RNA-Seq | 4.5 GB | link | |||
| — | CGND-HRA-00250_GCTCGGTA_ACBLRLANXX_L006_001.R1.fastq.gz | RNA-Seq | 5.1 GB | link | |||
| — | CGND-HRA-00251_TGGAACAA_ACBLRLANXX_L006_001.R1.fastq.gz | RNA-Seq | 4.5 GB | link | |||
| — | CGND-HRA-00252_AGCACCTC_ACBLRLANXX_L008_001.R1.fastq.gz | RNA-Seq | 4.8 GB | link | |||
| — | CGND-HRA-00255_TAGGATGA_ACBUUJANXX_L001_001.R1.fastq.gz | RNA-Seq | 6.5 GB | link | |||
| — | CGND-HRA-00256_GCCAAGAC_ACBUUJANXX_L002_001.R1.fastq.gz | RNA-Seq | 8.1 GB | link |