Ruben Cools from VIB-KU Leuven, Belgium presented at London Calling 2025 on “Bridging genotype and phenotype through long-read, single-molecule multiomics.” They are working on a high-throughput long-read single-cell open chromatin and transcriptome profiling method. The SPLOGGET approach prepares whole-genome, open chromatin and full-length transcriptome sequencing libraries for single cells. Cools explained that the method uses deep single-cell sequencing and Oxford Nanopore Technologies (ONT) read lengths. The nf-core/scdnalong and nf-core/scanoseq pipelines were created for analyses. Cools explained a case of a patient who suffered several relapses. The team was able to sequence samples from different timepoints to gain important insights. Pre CAR T and post CAR T RNA analyses revealed a potential mechanism of resistance against CD19 targeted CAR T-cells. The methodology used allows somatic variant calling at the single cell level. Cools explained that their approach successfully combined 10X and ONT sequencing to develop a long-read single-cell multiome profiling method that dives DNA reads by length enabling both accessibility profiling and comprehensive whole-genome analysis. The matched cDNA and DNA barcodes then allow for multi-modal integration.
