ALS Gene Expression Explorer

ALS Gene Expression Explorer

This interactive browser enables exploration of differential gene expression across multiple tissues in Amyotrophic Lateral Sclerosis (ALS). Users can query any gene to visualize expression differences between ALS cases and controls, examine associations with clinical variables including C9orf72 mutation status, age at death, and disease duration, and review full differential expression statistics across tissues.

The app is organized into two views:

• ALS vs Control: Boxplots and DEG statistics comparing ALS samples (bulk RNA-seq expression) to healthy controls across all available tissues.
• ALS Only Analysis: Expression scatter plots and DEG results within ALS cases, stratified by C9orf72 mutation status, age at death, and disease duration.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with substantial genetic and clinical heterogeneity that impedes therapeutic development. Large-scale multi-tissue genomic resources have transformed the study of neuropsychiatric and neurodegenerative diseases, but no equivalent resource exists for ALS. Here we present the full NYGC ALS Consortium dataset, combining whole-genome sequencing from 4,746 donors and bulk RNA-seq from 2,574 samples across 8 brain and spinal cord regions from 695 donors across the ALS disease spectrum. Our catalogue of small variants, structural variants, and short tandem repeats identified likely pathogenic mutations in 15.6% of ALS cases. Gene expression and mRNA splicing analysis across 5 major tissues reveals shared and region-specific features, highlighting microglial and T-cell dysregulation in the spinal cord. Mapping the genetic regulation of expression and splicing across tissues identified associations with 6 ALS risk loci, whereas allele-specific rare variant analysis detected expression effects for C9orf72 and OPTN. All data are immediately publicly available.

Pre-print available at:

🔗 medRxiv

Code available at:

https://github.com/Eastmanmd/AlsGeneBroswer/

Full data available at:

🔗 Metadata 🔗 Gene Expression Data 🔗 Splicing Data

Written & Designed By

AO

Ali Oku

Bioinformatics Analyst, Computational Biology

New York Genome Center (NYGC)