Provided are
DNA library preparation methods and compositions that duplicate a target
nucleic acid sequence. A target
DNA template including the target sequence is circularized via an end adapter to form a circular construct, which is bidirectionally extended by a
polymerase-mediated extension that is initiated at nick sites of the end adapter. Following
polymerase-mediated extension, a double-length
DNA template is formed that includes two copies of the target
DNA template (and hence two copies of the target sequence). Each strand of the double-length
DNA template includes a parental
polynucleotide strand joined to a newly synthesized
daughter strand copy of the parental
polynucleotide strand. Predetermined sequences can be included in the double-length
DNA template, such a primer sequences, unique molecule identifiers, and sequence indexes. Sequencing of the double-length DNA template can reveal genetic / epigenetic information associated with the target sequence. Also provided are methods to create asymmetric and multi-length DNA template constructs.