A method for investigating intra- and/or intermolecular interactions involving RNA is provided. The method includes a) synthesizing a RNA/DNA heteroduplex (RDH) comprising a RNA strand of interest paired to a DNA strand; b) binding a first end of the DNA strand and a corresponding first end of the RNA strand to a first element of a nanoscale manipulating device, and a second end of the DNA strand to a second element of the nanoscale manipulating device, leaving a second end of the RNA strand free; c) moving the first and second elements of the manipulating device apart from each other, stretching the DNA strand and causing the RNA strand to peel off the heteroduplex; and d) moving the first and second elements of the nanoscale manipulating device towards each other, allowing the DNA strand to relax and causing the RNA strand to bind again to it. Measurement of a force-displacement relationship during steps c) and d) provides information on intra- and/or intermolecular interactions involving the RNA strand. Also provided is an apparatus for carrying out the method.

Methods and compositions for performing a rolling circle amplification (RCA) reaction using circularized template comprising identifier sequences are provided. Sequencing is performed on the RCA product using a polymerase to incorporate a plurality of cognate nucleotides into the sequencing primer or an extension product thereof to generate an extension product.

Methods and compositions for performing a rolling circle amplification (RCA) reaction using circularized template comprising identifier sequences are provided. Sequencing is performed on the RCA product using a polymerase to incorporate a plurality of cognate nucleotides into the sequencing primer or an extension product thereof to generate an extension product.

Methods and materials are provided for detecting nucleic acid sequence differences including single nucleotide mutations or polymorphisms, one or more nucleotide insertions, and one or more nucleotide deletions in single molecule target members present in a test population of nucleic acid fragments. Heteroduplexes are formed between members of the test nucleic acid population and their corresponding complements provided in a pool of mismatch cleavage probes. Mismatched base pairs in the heteroduplexes are specifically cleaved and cleaved probe fragments are electronically detected to signal the present of the target members in the test population.

Methods and materials are provided for detecting nucleic acid sequence differences including single nucleotide mutations or polymorphisms, one or more nucleotide insertions, and one or more nucleotide deletions in single molecule target members present in a test population of nucleic acid fragments. Heteroduplexes are formed between members of the test nucleic acid population and their corresponding complements provided in a pool of mismatch cleavage probes. Mismatched base pairs in the heteroduplexes are specifically cleaved and cleaved probe fragments are electronically detected to signal the present of the target members in the test population.

Methods and compositions for performing a rolling circle amplification (RCA) reaction using circularized template comprising identifier sequences are provided. Sequencing is performed on the RCA product using a polymerase to incorporate a plurality of cognate nucleotides into the sequencing primer or an extension product thereof to generate an extension product.

Methods and compositions for performing a rolling circle amplification (RCA) reaction using circularized template comprising identifier sequences are provided. Sequencing is performed on the RCA product using a polymerase to incorporate a plurality of cognate nucleotides into the sequencing primer or an extension product thereof to generate an extension product.