Fig. 2
Auto-cycling proximity recording (APR) mechanisms. a The APR cycle creates molecular records of proximity from pairs of hairpin probes. Probe-specific primers are (step i in a) extended to Half-records and (ii) reversibly displaced, (iii) bind palindromic domains of nearby Half-records, and (iv) are extended on each other to create and release Full-records, regenerating the probes. See text for detailed description. b Copy-and-release hairpin (CRH) detail, depicting primer binding domain b explicitly but labeling the entire copied template simply as t. Shown is the mechanism of (state i in b) initial primer binding, (ii) extension, and (iii) random walk of the strand displacement branch. For this combination of primer bulge l T and Spacer9 stopper shown, the hairpin template strand t−b is computationally predicted to pair predominantly with the hairpin stem complement (iii, plot). See also Supplementary Fig. 1. c A more rapidly cycling hairpin does not utilize bulge l T or domain b, but instead uses a phosphorothioate (PS) bond before the final primer (a) nucleotide, in conjunction with synthetic nucleotide pair iso-dC/iso-dG as a stopper. See Supplementary Fig. 2 for sequences and Supplementary Note 1 for other considerations
