Mariela Cortes Lopez from the Weil Cornell Medicine and New York Genome Center presented at the Nanopore Community Meeting in Houston about “GoT-Splice: unraveling cell-type-specific impact of splicing factor mutations.” Cortes Lopez is investigating mutations in splicing factors. They started by explaining that cells accumulate mutations with age and, therefore, the genomes of cells are different. Some mutations are clonally expanded. Somatic mutations seem to be frequently found in splicing factors. Cortes Lopez said that in blood cancers, splicing alterations are abundant. However, most studies focus on bulk sequencing. This results in the incomplete reconstruction of transcriptomes. The team developed GoT-Splice, which builds on the 10X Genomics platform to amplify a mutation of interest and includes long-read sequencing. Long-read sequencing can help reconstruct the transcriptome from one cell. With this approach, Cortes Lopez and team noticed that mutant erythroid progenitor cells accumulate due to cell cycle and translation changes. With long-read data, the team noticed increased splicing of some transcripts only in mutant cells. Splicing factor mutations were also abundant in clonal hematopoieses. Cortes Lopez concluded that GoT-Splice profiles are a powerful tool for obtaining single-cell profiles for genotype, expression, surface markers, and more!
