Integrative multi-omic analysis identify new drivers and pathways in molecularly distinct subtypes of ALS

Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease. Increasing the chances of success for future clinical strategies requires more in-depth knowledge of the molecular basis underlying disease heterogeneity. We recently laid the foundation for a molecular taxonomy of ALS by whole genome expression profiling of motor cortex from sporadic ALS (SALS) patients [1-4]. Here, we analyzed genomic structural aberrations occurring in the same patients, by using a customized exon-centered comparative genomic hybridization array (aCGH) covering a large panel of ALS-related genes [5, 6]. Integrative analysis of copy number profiles with their associated transcriptomic data revealed subtype- specific genomic perturbations and candidate driver genes positively correlated with transcriptional signatures, hich might represent novel potential biomarkers and therapeutic targets. This study represents the first comprehensive "omics" analysis of molecular events characterizing SALS pathology, providing a road map to facilitate genome-guided personalized diagnosis and treatments for this devastating disease.