Tonight I watched the NCM Houston Update from Sissel Juul from Oxford Nanopore Technologies. The session is entitled “Covering all bases,” and Juul is the director of the applications team. The talk focused on variant calling mostly on the PromethION. About a year and a half ago, the telomere-to-telomere consortium published the T2T assembly in Science. Juul explained that a lot of the regions sequenced were repetitive and part of the “dark genome,” areas inaccessible to short reads or repetitive. Many of the genes uncovered can be used for phamacogenetic studies. Determining which variants people have is important in drug treatment. Long reads improve SNP calling and mapping in repetitive regions. Reads can be phased or resolved by haplotypes. With longer reads, often two or more variants can be used and assigned to a haplotype. Next, Juul explained that reads can help resolve repeat expansions, SVs, and methylation. Deletions can be detected precisely with longer reads. Spinal Muscular Atrophy (SMA) is a gene that is “notoriously difficult” to sequence, Juul explained. Accurate copy-number and detection of SV is possible for this and other genes with the ONT platform. Juul explained that they are generating a tool to help call and determine copy number of these genes. Juul shared an example of genes with differences in methylation for those from tumor samples. Without having to perform tissue biopsies, fragment length of cell free DNA can be analyzed. The 3D conformation of the genome can be studied with Pore-C. Juul ended with Telo-seq: native sequencing of individual telomeres and sub telomeric regions. The assay can be used to analyze telomere length and methylation profiles. This twenty-minute update was full of examples of human genome analysis at different levels using long-read sequencing. I a hoping to apply some of the tools and approaches to other genomes/organisms.
