Multi-omics approach to study complex diseases: a monozygotic discordant for ALS twin pair study and Pedigree project

To disentangle biological bases of complex diseases, a multi-omics approach is a valuable resource. In this work, we applied both an early and a late strategy to study two neurological diseases with a complex aetiology: Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS). We analysed a monozygotic twin pair discordant for ALS to investigate genetic and epigenetic factors underlying ALS. We performed a whole exome sequencing (WES), a RNA sequencing and a genome-wide methylation study. Then, we applied a late approach to integrate all the three omics, while an early strategy has been applied only to combine transcriptomics and epigenetics. We identified likely benign or of uncertain significance SNV and CNV, 42 DEGs involved in pathways linked to immune system and differentially methylated probes involved in developmental processes (brain, axon). Early integration with MOFA showed some limitations, so a late approach would fit better our study. The second project is an Italian multicentric case-control study aimed at identifying genetic and environmental risk factors associated to the pediatric form of MS, which is rare and poorly characterised. Pediatric subjects offer a unique opportunity to gain clinical and biological data in close proximity to the actual disease onset. We investigated the role of gut microbiota (16S sequencing), the epigenetic profiles (EPIC Array), genetic (GWAS) and environmental factors in PedMS, matched HC and adultMS with onset < 18 years. We identified enriched and depleted species in PedMS; DMPs and regions already described in literature, and suggestive and genome-wide significant SNPs. We have analysed several omics individually underlining differences between PedMS and HC. We have already performed a preliminary late integration analysis and we are combining genetic, epigenetic and metagenomic data by an early integration strategy to identify latent factors that could explain PedMS pathogenesis.