Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized
by the death of motor neurons, the aetiology of which is essentially unknown. Here,
we present an integrative epigenomic study in blood samples from seven clinically
characterised sporadic ALS patients to elucidate molecular factors associated with
the disease. We used clinical exome sequencing (CES) to study DNA variants, DNA-RNA
hybrid immunoprecipitation sequencing (DRIP-seq) to assess R-loop distribution, and
reduced representation bisulfite sequencing (RRBS) to examine DNA methylation changes.
The above datasets were combined to create a comprehensive repository of genetic and
epigenetic changes associated with the ALS cases studied. This repository is well-suited
to unveil new correlations within individual patients and across the entire patient
cohort. The molecular attributes described here are expected to guide further mechanistic
studies on ALS, shedding light on the underlying genetic causes and facilitating the
development of new epigenetic therapies to combat this life-threatening disease.
