Full-length transcript characterization of SF3B1 mutation in chronic lymphocytic leukemia reveals downregulation of retained introns

While splicing changes caused by somatic mutations in SF3B1 are known, identifying full-length isoform changes may better elucidate the functional consequences of these mutations. We report nanopore sequencing of full-length cDNA from CLL samples with and without SF3B1 mutation, as well as normal B cell samples, giving a total of 149 million pass reads. We present FLAIR (Full-Length Alternative Isoform analysis of RNA), a computational workflow to identify high-confidence transcripts, perform differential splicing event analysis, and differential isoform analysis. Using nanopore reads, we demonstrate differential 3' splice site changes associated with SF3B1 mutation, agreeing with previous studies. We also…

• FF
  Ford Foundation
• PC
  Pew Charitable Trusts
• DR
  Damon Runyon Cancer Research Foundation
• LA
  Leukemia and Lymphoma Society
• UO
  University of California, Santa Cruz
• NI
  National Institutes of Health

  Awards: T32GM008646, 2R25GM058903, R01HG010053
• NH
  National Human Genome Research Institute

  Awards: 5T32HG008345, R01HG010053
• NC
  National Cancer Institute

  Award: 1U10CA180861-01
• NI
  National Institute of General Medical Sciences

  Awards: T32GM008646, 2R25GM058903