Philipp Rescheneder, the Senior Director of Applications for Bioinformatics at Oxford Nanopore Technologies, presented at the Nanopore Community Meeting in Boston. They presented an update based on an analysis of Rett syndrome, a rare genetic disorder that causes severe mental and physical disability. Rescheneder defined multi-omics for this study as the use of genomics, epigenomics, and transcriptomics. Rescheneder noted that there are canonical bases, native modifications, and synthetic modifications that can be used to mark regions of interest with 6mA, for example. This study used LSK, Pore-C, and cDNA sequencing of nine cell lines! Rescheneder explained that most Rett syndrome cases are caused by mutations in the MECP2 gene. The EPI2ME report identified a repeat expansion in the RFC1 gene. Rescheneder then explained phasing genetic and epigenetic variation of these samples. Rescheneder described the case of a mother whose son and daughter were affected by Rett syndrome, but she wasn’t… and the father’s DNA was unavailable. The mother’s cDNA does not have transcripts of the variant. The daughter and son have 13% and 100% transcription of the pathogenic variant. Rescheneder explained that this is because of the X chromosome inactivation. One haplotype in the mother is completely silence, and the other isn’t. Phasing also allows for the identification of inactivation escape. SMC1A escapes complete silencing in one strain. Rescheneder summarized the study by noting that native modifications can be obtained. Synthetic mutations can help explore chromatin structure. Rescheneder did say more data would likely be available soon and released at London Calling. The approach of synthetic modifications is one that I don’t know much about and would like to better understand!
