Abstract: The present disclosure provides methods and systems for detecting multiple different nucleotides in a sample. In particular, the disclosure provides for detection of multiple different nucleotides in a sample utilizing fewer detection moieties than the number of nucleotides being detected and/or fewer imaging events than the number of nucleotides being detected.

Abstract: A sensor having a first electrode and a second electrode operably connected by a conduction channel, wherein a polymerase, primed template nucleic acid and nucleotide form a stabilized ternary complex that is immobilized in or on the conduction channel, whereby association and dissociation of the ternary complex is detected due to changes in electrical properties of the sensor. Identification of the nucleotide type that participates in the complex indicates the identity of the next template base in the template. Repeated cycles of extending the primer and detecting stabilized ternary complexes can allow determination of the sequence of nucleotides for the template.

Abstract: The present disclosure provides methods and systems for detecting multiple different nucleotides in a sample. In particular, the disclosure provides for detection of multiple different nucleotides in a sample utilizing fewer detection moieties than the number of nucleotides being detected and/or fewer imaging events than the number of nucleotides being detected.

Abstract: A portable detector is disclosed for detecting certain analytes of interest, such as genetic material (e.g., nucleic acids). The detector includes a reading component for the detection of the analytes, and control circuitry for controlling operation of the reading component. Processing circuitry may be included to perform both primary analysis of acquired data, and where desired, secondary analysis. Where desired, some or all of the computationally intensive tasks may be off-loaded to enhance the portability and speed of the device. The device may incorporate various types of interface, technologies for reading and analysis, positioning system interfaces, and so forth. A number of exemplary use cases and methods are also disclosed.

Abstract: A portable detector is disclosed for detecting certain analytes of interest, such as genetic material (e.g., nucleic acids). The detector includes a reading component for the detection of the analytes, and control circuitry for controlling operation of the reading component. Processing circuitry may be included to perform both primary analysis of acquired data, and where desired, secondary analysis. Where desired, some or all of the computationally intensive tasks may be off-loaded to enhance the portability and speed of the device. The device may incorporate various types of interface, technologies for reading and analysis, positioning system interfaces, and so forth. A number of exemplary use cases and methods are also disclosed.

Abstract: The present invention provides methods and compositions for carrying out nucleic acid sequencing, particularly paired-end sequencing. The methods use concatemeric sequencing templates that can be produced by rolling circle amplification of asymmetric circular nucleic acids having a central double-stranded region comprising a target nucleic acid sequence that is connected at each end to form a circular construct.

Abstract: Embodiments disclosed herein provide methods for constructing a DNA profile comprising: providing a nucleic acid sample, amplifying the nucleic acid sample with a plurality of primers that specifically hybridize to at least one target sequence comprising a SNP and at least one target sequence comprising a tandem repeat, and determining the genotypes of the at least one SNP and at least one tandem repeat in the amplification products, thereby constructing the DNA profile of the nucleic acid sample. Embodiments disclosed herein further provide a plurality of primers that specifically hybridize to at least one short target sequence and at least one long target sequence in a nucleic acid sample, wherein amplifying the nucleic acid sample using the plurality of primers in a single reaction results in a short amplification product and a long amplification product, wherein each of the plurality of primers comprises one or more tag sequences.

Abstract: A method for sequencing a population of nucleic acids, which includes (a) binding the population of nucleic acids with a fractionally labeled mixture of nucleotides, thereby forming a fractionally labeled population of nucleic acids, wherein the mixture includes nucleotide cognates for a common base type in the templates, and wherein a fraction of the nucleotide cognates for the common base type in the mixture are exogenously labeled nucleotides that produce a signal that is not produced by other nucleotide cognates for the common base type in the mixture; (b) detecting the signal from the fractionally labeled population of nucleic acids; and (c) repeating (a) and (b) using a second mixture of the fractionally labeled nucleotides, wherein the fraction of the exogenously labeled nucleotides is higher in the second mixture.

Abstract: Provided includes methods, compositions and systems for single molecule seeding and amplification on a flow cell. In some embodiments, nucleic acids are isothermally seeded and amplified on a flow cell comprising multiple binding areas (e.g., pads), resulting in an ensemble of substantially the same amplified molecules on each of the binding areas.

Abstract: A method including (a) providing an amplification reagent including an array of sites, and a solution having different target nucleic acids; and (b) reacting the amplification reagent to produce amplification sites each having a clonal population of amplicons from a target nucleic acid from the solution. The reacting can include simultaneously transporting the nucleic acids to the sites at an average transport rate, and amplifying the nucleic acids that transport to the sites at an average amplification rate, wherein the average amplification rate exceeds the average transport rate. The reacting can include producing a first amplicon from a nucleic acid that transports to each of the sites, and producing subsequent amplicons from the nucleic acid or from the first amplicon, wherein the average rate at which the subsequent amplicons are generated exceeds the average rate at which the first amplicon is generated.

Abstract: Provided herein is a method for distinguishing an aberrant methylation level for DNA from a first cell type, including steps of (a) providing a test data set that includes (i) methylation states for a plurality of sites from test genomic DNA from at least one test organism, and (ii) coverage at each of the sites for detection of the methylation states; (b) providing methylation states for the plurality of sites in reference genomic DNA from one or more reference individual organisms, (c) determining, for each of the sites, the methylation difference between the test genomic DNA and the reference genomic DNA, thereby providing a normalized methylation difference for each site; and (d) weighting the normalized methylation difference for each site by the coverage at each of the sites, thereby determining an aggregate coverage-weighted normalized methylation difference score.

Abstract: The invention provides methods for controlling the density of different molecular species on the surface of a solid support. A first mixture of different molecular species is attached to a solid support under conditions to attach each species at a desired density, thereby producing a derivatized support having attached capture molecules. The derivatized support is treated with a second mixture of different molecular species, wherein different molecular species in the second mixture bind specifically to the different capture molecules attached to the solid support. One or more of the capture molecules can be reversibly modified such that the capture molecules have a different activity before and after the second mixture of molecular species are attached. In particular embodiments, the different molecular species are nucleic acids that are reversibly modified to have different activity in an amplification reaction.

Abstract: A method including (a) providing an amplification reagent including an array of sites, and a solution having different target nucleic acids; and (b) reacting the amplification reagent to produce amplification sites each having a clonal population of amplicons from a target nucleic acid from the solution. The reacting can include simultaneously transporting the nucleic acids to the sites at an average transport rate, and amplifying the nucleic acids that transport to the sites at an average amplification rate, wherein the average amplification rate exceeds the average transport rate. The reacting can include producing a first amplicon from a nucleic acid that transports to each of the sites, and producing subsequent amplicons from the nucleic acid or from the first amplicon, wherein the average rate at which the subsequent amplicons are generated exceeds the average rate at which the first amplicon is generated.

Abstract: The invention provides methods for controlling the density of different molecular species on the surface of a solid support. A first mixture of different molecular species is attached to a solid support under conditions to attach each species at a desired density, thereby producing a derivatized support having attached capture molecules. The derivatized support is treated with a second mixture of different molecular species, wherein different molecular species in the second mixture bind specifically to the different capture molecules attached to the solid support. One or more of the capture molecules can be reversibly modified such that the capture molecules have a different activity before and after the second mixture of molecular species are attached. In particular embodiments, the different molecular species are nucleic acids that are reversibly modified to have different activity in an amplification reaction.

Abstract: The present disclosure provides methods and systems for detecting multiple different nucleotides in a sample. In particular, the disclosure provides for detection of multiple different nucleotides in a sample utilizing fewer detection moieties than the number of nucleotides being detected and/or fewer imaging events than the number of nucleotides being detected.

Abstract: Presented are methods and compositions for spatial detection and analysis of nucleic acids in a tissue sample. The methods can enable the characterization of transcriptomes and/or genomic variations in tissues while preserving spatial information about the tissue.

Abstract: Presented are methods and compositions for spatial detection and analysis of nucleic acids in a tissue sample. The methods can enable the characterization of transcriptomes and/or genomic variations in tissues while preserving spatial information about the tissue.

Abstract: The present disclosure provides methods and systems for detecting multiple different nucleotides in a sample. In particular, the disclosure provides for detection of multiple different nucleotides in a sample utilizing fewer detection moieties than the number of nucleotides being detected and/or fewer imaging events than the number of nucleotides being detected.

Abstract: A method for detecting nucleic acids by (a) providing a sample having target nucleic acids, each nucleic acid having contiguous first, second, and third domains; (b) contacting the sample with probe sets to form hybridization complexes, wherein each probe set includes (i) a first probe having a sequence that is complementary to the first domain; and (ii) a second probe having a sequence substantially complementary to the third domain; (c) extending the first probes along the second domains of the complexes while the complexes are immobilized on a solid support; (d) ligating the extended first probes to the second probes to form templates; (e) amplifying the templates with primers that are complementary to the first and second priming sequences to produce amplicons; and (f) detecting the amplicons on the surface of a nucleic acid array.

Abstract: A method for sequencing a population of nucleic acids, which includes (a) binding the population of nucleic acids with a fractionally labeled mixture of nucleotides, thereby forming a fractionally labeled population of nucleic acids, wherein the mixture includes nucleotide cognates for a common base type in the templates, and wherein a fraction of the nucleotide cognates for the common base type in the mixture are exogenously labeled nucleotides that produce a signal that is not produced by other nucleotide cognates for the common base type in the mixture; (b) detecting the signal from the fractionally labeled population of nucleic acids; and (c) repeating (a) and (b) using a second mixture of the fractionally labeled nucleotides, wherein the fraction of the exogenously labeled nucleotides is higher in the second mixture.