Mann, K.M. et al. Nat. Biotechnol. 34, 962–972 (2016).

Mutations that underlie cancers are often obscured by genetic heterogeneity, and sequencing-based approaches typically recover many 'passenger' loci that are not responsible for cancer progression. Starting with a mouse model of acute myeloid leukemia (AML), Mann et al. have developed Sleeping Beauty capture hybridization sequencing (SBCapSeq), a functional screening method that couples mutagenesis from an active Sleeping Beauty transposon with sequencing. SBCapSeq uses random fragmentation, size selection and liquid-phase hybridization capture of active transposon sequences (and blocking of unmobilized transposon sequences) to sequence insertions in bulk or single mouse tumor cells. The researchers show that the method recovered AML genes in a semiquantitative manner, allowing them to identify major clonal populations and combinations of driver genes from as few as 26 cells.