Abstract: A method for making an asymmetrically-tagged sequencing library is provided. In some embodiments, the method may comprise: obtaining a symmetrically-tagged library of cDNA or genomic DNA fragments, hybridizing a tailed first primer to the 3? sequence tag of the library and extending the same to produce primer extension products, and amplifying the primer extension products using a prior of tailed primers to produce asymmetrically-tagged library.

Abstract: Provided herein, among other things, are compositions for improving signal-to-noise in hybridization to oligonucleotide arrays. In some embodiments, the composition may comprise a population of indexing oligonucleotides of formula X-Y, where the sequences of region X hybridize to an array and the sequences of region Y hybridize to distinct sites within a genomic region, transcript, set of transcripts, or complement of the same. Use of these oligonucleotides increases signal, reduces background and smoothens array hybridization analyses. Methods and kits that employ the compositions are also provided.

Abstract: Provided herein, among other things, is a method for producing a ligation product on a support. In some embodiments, the method may comprise hybridizing a first double-stranded oligonucleotides and a second double-stranded oligonucleotide to a substrate comprising surface-tethered oligonucleotides and ligating the distal ends of the first and second double-stranded oligonucleotides together, thereby producing a first ligation product that is tethered to the support at both ends.

Abstract: Systems and methods for displaying gene- and/or protein-related data with respect to chromosome maps at locations identifying relevant positioning of the genes with which the gene- and/or protein related data are associated. Multiple experiments may be plotted onto the display adjacent one or more chromosome maps. Automatic extraction of genomic location, based on accession numbers or other unique identifiers and cross connection with expression data is provided. Statistical assessments of correlations between expression and genome localization may be performed. Zooming capabilities, thumbnail/fullview toggling, browsability and linked data may be included as features of the visualization systems described.

Abstract: Described herein, among other things, is an adapter comprising a population of first oligonucleotides, a second oligonucleotide and a third oligonucleotide, wherein the first oligonucleotides, the second oligonucleotide and the third oligonucleotide are hybridized together to produce a complex that comprises: (i) a first end comprising a transposase recognition sequence, (ii) a central single-stranded region of variable sequence and (iii) a second end comprising sequences that are non-complementary. A method, as well as a kit for practicing the method, are also provided.

Abstract: The present disclosure provides methods for barcoding a plurality of DNA samples using a microarray of barcode-containing transposase complexes. In some embodiments, the DNA samples and transposase complexes are present in aqueous droplets on the surfaces of opposing substrates, which allows a single DNA sample droplet to be combined with a single transposase-complex droplet. The barcoded DNA in the combined droplets can be used for any number of purposes, including as templates for amplification and sequencing.

Abstract: This present disclosure provides methods and compositions for multiplex amplification, e.g., PCR, of DNA samples compartmentalized on the surface of an array. In certain aspects, the method includes providing a solid substrate having features of immobilized forward and reverse primer pair constructs therein for amplifying a target polynucleotide sequence, contacting the plurality of features with a corresponding nucleic acid sample, and incubating the contacted features under conditions to allow release of the forward and reverse primer constructs and amplification of the desire target polynucleotide. The release of the primer constructs from the substrate can be done prior to or during the incubating step.

Abstract: The present disclosure provides methods for barcoding a plurality of DNA samples using a microarray of barcode-containing transposase complexes. In some embodiments, the DNA samples and transposase complexes are present in aqueous droplets on the surfaces of opposing substrates, which allows a single DNA sample droplet to be combined with a single transposase-complex droplet. The barcoded DNA in the combined droplets can be used for any number of purposes, including as templates for amplification and sequencing.

Abstract: A method for analyzing a sequence comprising a SNP site is provide. In general terms, the method comprises: a) contacting a first DNA sample with a first restriction enzyme to provide DNA fragments, wherein: i) the first restriction enzyme cleaves the sequence only if a first allele of a SNP is present at the SNP site; b) end-labeling the DNA fragments to produce an end-labeled sample; c) hybridizing the end-labeled sample to an array comprising a probe sequence; and d) comparing the amount of hybridization between the digested sample and the probe sequence to a reference signal.

Abstract: A sample probe includes a tip including a distal end for penetrating a cellular membrane, an opening located at or proximal to the distal end, and tip microchannels extending through the tip and communicating with the opening; and a body adjoining the tip and including body microchannels, wherein at least one of the body microchannels communicates with at least one of the tip microchannels. A method for sampling intracellular material includes inserting a probe tip through a cellular membrane; aspirating intracellular material from the cell, through an opening of the tip, and into a first microchannel of the tip; flowing isolator fluid from a second microchannel of the tip into the first microchannel to form a plug of intracellular material; and aspirating the plug and the isolator fluid through the first microchannel.

Abstract: Provided herein is a method comprising: (a) obtaining a mixture of multiple sets of oligonucleotides, wherein the oligonucleotides within each set each comprise a terminal indexer sequence and can be assembled to produce a synthon; and (b) hybridizing the oligonucleotide mixture to an array, thereby spatially-separating the different sets of oligonucleotides from one another. In some embodiments the method may comprise (c) contacting the array with a solution, thereby producing, for each feature bound by the oligonucleotides, a discrete droplet comprising the feature and, optionally, placing an immiscible liquid over the droplets, thereby producing, for each feature bound by the oligonucleotides, a discrete reaction chamber defined by a droplet. The method may further comprise incubating the array under conditions by which a synthon is assembled in each of the reaction chambers. Other embodiments are also provided.

Abstract: Provided herein, among other things, is a method comprising: (a) obtaining a mixture of multiple sets of oligonucleotides, wherein the oligonucleotides within each set each comprise a terminal indexer sequence can be assembled to produce a synthon; and (b) hybridizing the oligonucleotide mixture to an array, thereby spatially-separating the different sets of oligonucleotides from one another. Other embodiments are also provided.

Abstract: Provided is an emulsion comprising: (a) droplets that contain a single polymeric compound or a pre-defined mixture thereof, and (b) an immiscible liquid, wherein: (i) each of the droplets comprises multiple molecules of the compound(s) contained therein; and the droplets do not contain monomeric precursors for the polymeric compound. A method for making the emulsion is also provided.

Abstract: A composition comprising population of labeled oligonucleotides is provided herein. In some embodiments, the probes are of the formula: T1-V-T2, wherein: the nucleotide sequence of the V region varies in said population; the V regions of the different oligonucleotides hybridize to sites that are tiled across a sequence in a target nucleic acid; the T1 and T2 regions do not hybridize with said target nucleic acid; within each oligonucleotide of the population, the T1 and T2 regions are not complementary; and within each oligonucleotide of the population, the T1 region is complementary to the T2 region of at least one of other oligonucleotide of the population. Also provided is a method that comprises hybridizing the population of labeled oligonucleotides with a target nucleic acid to produce a complex.

Abstract: Provided herein is a proximity assay that, in certain embodiments, involves: (a) hybridizing a first oligonucleotide and a second oligonucleotide with a target nucleic acid, wherein the first oligonucleotide comprises: i. a region that is complementary to a first sequence in the target nucleic acid and ii. a barcode sequence; and the second oligonucleotide comprises i. a region that is complementary to a second region in the target and ii. the complement of the barcode sequence; and (b) detecting hybridization between the barcode sequence and the complement of the barcode sequence, wherein hybridization between the barcode sequence and the complement of the barcode sequence indicates that the first and second target sequences are proximal to one another in the sample.

Abstract: A sample probe includes a tip including a distal end for penetrating a cellular membrane, an opening located at or proximal to the distal end, and tip microchannels extending through the tip and communicating with the opening; and a body adjoining the tip and including body microchannels, wherein at least one of the body microchannels communicates with at least one of the tip microchannels. A method for sampling intracellular material includes inserting a probe tip through a cellular membrane; aspirating intracellular material from the cell, through an opening of the tip, and into a first microchannel of the tip; flowing isolator fluid from a second microchannel of the tip into the first microchannel to form a plug of intracellular material; and aspirating the plug and the isolator fluid through the first microchannel.

Abstract: A test system includes an optical medium, a binding agent capable of capturing a target complex, and a light detector. The optical medium provides a light path, and the binding agent is positioned to hold the target complex in an evanescent field created by propagation of light along the light path. The complex interacts with the evanescent field and emits light that the detector positioned to detect. The optical medium and the detector can be included in an optical integrated circuit where detected light passes through the optical medium transverse to the direction of the light path.

Abstract: Certain embodiments described in this disclosure relate to a method of sample analysis. In certain cases, the method comprises: a) contacting a genomic sample comprising double-stranded genomic DNA with a first restriction endonuclease that recognizes a nucleotide sequence that comprises a SNP site in the double stranded genomic DNA, wherein: i. the restriction endonuclease cleaves the genomic DNA at the sequence regardless of the allele of the SNP present at the SNP site; and ii. cleavage of the sequence by the restriction enzyme creates a 5? overhang that comprises the SNP site; b) contacting the digested genomic sample with a extension enzyme and a first labeled nucleotide that is used by the extension enzyme to fill in the overhang only if the overhang comprises a first allele of the SNP.

Abstract: Methods for clustering a data set from a biological assay are provided. Aspects of the methods include applying statistical analyses to bisected subsets of the data at selected cut-of values to identify one or more break points in the data set. In certain aspects, the statistical analyses employed are based on determining the p-values of two-tailed t-tests calculated using the bisected data at each cut-off value. Aspects of the invention further include computer programming and systems which are configured to cluster data sets from biological assays according to the subject methods.

Abstract: A method of genome analysis is provided. In certain embodiments, the method comprises: a) contacting a double-stranded genomic DNA with a site-specific nicking endonuclease that recognizes a sequence comprising a single nucleotide polymorphism (SNP), in which the endonuclease nicks the genomic DNA at a nick site only if a first allele of the SNP is present; b) denaturing the genomic sample; c) contacting the denatured genomic sample with an array comprising a first probe and a second probe, in which nicking results in less binding of the denatured sample to the first probe relative to a sample that is not nicked; and d) comparing the amount of hybridization to the first probe to the amount of hybridization to said second probe, in which decreased binding of the denatured genomic samples to the first probe relative to the second probe indicates that the first allele of the SNP is present.