Uncovering RNA splicing's cell-specific impact on clonal blood disorders with GoT-Splice

The utility of long reads is well documented in studying complex genomic regions, structural variation, epigenetic modifications and transcriptomics. More specifically, long-read are increasing our understanding of RNA splicing factors. Although the regulation of splicing factors affects hematopoiesis, the role of dysregulated RNA splicing in clonal blood disorders (such as myelodysplastic syndromes (MDS) and other blood cancers) remains unclear.

In this webinar, Dr. Mariela Cortés López presented a novel approach, GoT-Splice, developed by the Landau lab at the New York Genome Center in collaboration with the Abdel-Wahab lab at MSKCC. The method integrates genotyping of transcriptomes (GoT) with Oxford Nanopore long-read single-cell transcriptome profiling and proteogenomics. GoT-Splice comprehensively profiles transcriptomes, surface proteins, somatic mutations and full-length RNA splicing at single-cell resolution.

The webinar presented a case study where GoT-Splice was used to study hematopoietic progenitors from MDS patients with mutations in the splicing factor SF3B1 and the findings that collectively demonstrated the power of GoT-Splice in delineating the cell-type-specific impact of somatic mutations on RNA splicing.

Authors: Mariela Cortés López, PhD. Postdoctoral Associate, Weill Cornell Medicine and New York Genome Center