Bioinformatic approaches to the identification of genomic sequences having G-quadruplex forming potential (QFP) has enabled important tests of the structure of these sequences in vitro and of their behavior under conditions where the formation or function of G-quadruplexes is modulated in vivo. Several similar approaches to identifying intramolecular QFP (i.e. forming among G-runs on one strand of DNA) have been developed previously, but none appears to perfectly predict G-quadruplex formation. Here we describe a new approach, which complements and differs from prior approaches in that it identifies motifs containing G-runs on both strands of duplex DNA that could contribute to G-quadruplex structures. We call these motifs duplex-derived interstrand QFP (ddiQFP), and illustrate their potential applications by describing their genomic distribution and an example of their correspondence to loci targeted by a G-quadruplex-unwinding DNA helicase in yeast.

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