Duplex Proximity Sequencing (Pro-Seq): A method to improve DNA sequencing accuracy without the cost of molecular barcoding redundancy
(A) Linked molecules are bound to the flow cell in close proximity to each other and form a single cluster as the size scale of the linker is much smaller than the size of a cluster. Following standard cluster generation, the bound fragments are extended and the linked template washed off (they do not interfere with flow cell function). After extension, bridge amplification proceeds as normal, with each cluster represented by multiple copies of the same starting molecule. (B) Clusters are sequenced, automatically generating an average or consensus of each base position, eliminating errors that occur as a small fraction of a cluster. In the case where the error signal is of similar scale to the true signal, error positions can be identified as mixed bases and masked (‘M’).