Sequencing small genomic targets with high efficiency and extreme accuracy

Nat Methods. 2015 May;12(5):423-5. doi: 10.1038/nmeth.3351. Epub 2015 Apr 6.


The detection of minority variants in mixed samples requires methods for enrichment and accurate sequencing of small genomic intervals. We describe an efficient approach based on sequential rounds of hybridization with biotinylated oligonucleotides that enables more than 1-million-fold enrichment of genomic regions of interest. In conjunction with error-correcting double-stranded molecular tags, our approach enables the quantification of mutations in individual DNA molecules.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • DNA / genetics*
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic
  • Genetic Loci*
  • Genetic Variation
  • Genomics / methods*
  • Humans
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / metabolism
  • Mutation
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sequence Analysis, DNA / methods*


  • DNA

Associated data

  • BioProject/PRJNA275267