Duplex Sequencing uses specialized adapters to uniquely tag both strands of individual DNA duplexes in a population. This allows identification and comparison of sequencing reads derived from amplified copies of each strand of a particular molecule of origin. Errors (red bases) that occur during PCR or sequencing are only present on reads from one strand whereas true mutations (black bases) are present on each strand and are complementary in nature. Duplex error correction reduces sequencing error rate to below one in ten million and eliminates noise that is inherent in standard Next Generation Sequencing (below).
Resistance mutation apparent before drug failure using DS
Duplex Sequencing reveals a low-frequency mutation known to cause imatinib resistance in chronic myeloid leukemia. All other apparent mutations seen with standard DNA sequencing were errors and obscured the presence of this true mutation. Had this mutation been recognized at the time, an alternative, non-cross resistant therapy could have been selected, potentially preventing relapse.