This disclosure provides a method of determining a sequence of nucleotides for a nucleic acid template. The method can include the steps of contacting the nucleic acid template with a conformationally labeled polymerase and at least four different nucleotide species under conditions wherein the conformationally labeled polymerase catalyzes sequential addition of the nucleotide species to form a nucleic acid complement of the nucleic acid template, wherein the sequential addition of each different nucleotide species produces a conformational signal change from the conformationally labeled polymerase and wherein the rate or time duration for the conformational signal change is distinguishable for each different nucleotide species; detecting a series of changes in the signal from the conformationally labeled polymerase under the conditions; and determining the rates or time durations for the changes in the signal, thereby determining the sequence of nucleotides for the nucleic acid template.

This disclosure provides a method of determining a sequence of nucleotides for a nucleic acid template. The method can include the steps of contacting the nucleic acid template with a conformationally labeled polymerase and at least four different nucleotide species under conditions wherein the conformationally labeled polymerase catalyzes sequential addition of the nucleotide species to form a nucleic acid complement of the nucleic acid template, wherein the sequential addition of each different nucleotide species produces a conformational signal change from the conformationally labeled polymerase and wherein the rate or time duration for the conformational signal change is distinguishable for each different nucleotide species; detecting a series of changes in the signal from the conformationally labeled polymerase under the conditions; and determining the rates or time durations for the changes in the signal, thereby determining the sequence of nucleotides for the nucleic acid template.

A method for determining the presence of an allele, including (a) binding a polymerase to a double stranded nucleic acid that includes a primer hybridized to a template, the template including a first allele of a locus; (b) adding a nucleotide to the primer via catalytic activity of the polymerase, thereby producing an extended nucleic acid; (c) dissociating the polymerase from the extended nucleic acid; (d) detecting dissociation of the polymerase from the extended nucleic acid; and (e) comparing the dissociation of the polymerase from the extended nucleic acid to dissociation of the polymerase from a second double stranded nucleic acid, the second double stranded nucleic acid including a primer hybridized to the same position of the locus as the primer of the extended nucleic acid.

A method for determining the presence of an allele, including (a) binding a polymerase to a double stranded nucleic acid that includes a primer hybridized to a template, the template including a first allele of a locus; (b) adding a nucleotide to the primer via catalytic activity of the polymerase, thereby producing an extended nucleic acid; (c) dissociating the polymerase from the extended nucleic acid; (d) detecting dissociation of the polymerase from the extended nucleic acid; and (e) comparing the dissociation of the polymerase from the extended nucleic acid to dissociation of the polymerase from a second double stranded nucleic acid, the second double stranded nucleic acid including a primer hybridized to the same position of the locus as the primer of the extended nucleic acid.

A biomolecule is more easily and reliably reciprocated in a nanopore. An adapter molecule that directly or indirectly binds to a biomolecule to be analyzed comprises a three-dimensional structure formation domain consisting of a single-stranded nucleotide.

A biomolecule is more easily and reliably reciprocated in a nanopore. An adapter molecule that directly or indirectly binds to a biomolecule to be analyzed comprises a three-dimensional structure formation domain consisting of a single-stranded nucleotide.

A method for matching a three-dimensional first image of at least one discrete entity with a three-dimensional second image of the at least one discrete entity is provided. The at least one discrete entity includes a biological sample and a plurality of constituent parts of a marker. The method includes: generating a first representation of the marker from the first image; generating a second representation of the marker from the second image; and based upon the representations matching, matching the first image with the second image; or based upon the representations not matching, rejecting the match. Generating the representations includes determining vectors from at least one reference item to at least some of the constituent parts of the marker, determining for the vectors at least one value of a property, and generating the representations of the marker based on a frequency of the at least one value of the property.

A method for matching a three-dimensional first image of at least one discrete entity with a three-dimensional second image of the at least one discrete entity is provided. The at least one discrete entity includes a biological sample and a plurality of constituent parts of a marker. The method includes: generating a first representation of the marker from the first image; generating a second representation of the marker from the second image; and based upon the representations matching, matching the first image with the second image; or based upon the representations not matching, rejecting the match. Generating the representations includes determining vectors from at least one reference item to at least some of the constituent parts of the marker, determining for the vectors at least one value of a property, and generating the representations of the marker based on a frequency of the at least one value of the property.

Provided herein are compositions and methods for assembling multiple DNA molecules into a linear concatemer, with applications to nanopore sequencing of DNA sequence variations.

Provided herein are compositions and methods for assembling multiple DNA molecules into a linear concatemer, with applications to nanopore sequencing of DNA sequence variations.