Abstract: A method of sample analysis is provided. In certain embodiments the method comprises: a) obtaining from a diploid individual a chromosomal sample that comprises maternally-derived chromosomes and homologous paternally-derived chromosomes; b) determining the parent of origin of a first chromosome of the sample by detecting a parent-specific copy number variation relative to a second chromosome that is homologous to the first chromosome; c) isolating the first chromosome; and d) genotyping the first chromosome.

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: A method of estimating the allele-specific copy number of a SNP in a test genome is provided. In certain embodiments, the method involves: a) calculating a plurality of probability distribution functions that fit a plurality of log ratios indicating which alleles of a plurality of single nucleotide polymorphisms (SNPs) are present in diploid regions of a test and reference genome; and b) estimating the allele-specific copy number of a SNP of the test genome using said plurality of probability distribution functions.

Abstract: A method for analyzing a sequence comprising a SNP site is provide.

Abstract: Methods and systems for identifying and selecting nucleic acid probes for detecting a target with a nucleic acid probe array or comparative genome hybridization microarray, comprising selecting a plurality of potential target sequences, generating a plurality of candidate probes from the target sequences, filtering the plurality of candidate probes by analyzing candidate probes for selected probe properties in silico. Microarrays comprising probes selected by the methods of the invention are particularly useful for comparative genome hybridization and location analysis.

Abstract: Methods of evaluating candidate CGH probe nucleic acid sequences are provided. Aspects of the methods include providing a candidate CGH probe nucleic acid sequence for a target sequence of a copy number variation (CNV) of a genome. A proximity score is then determined for the candidate CGH probe nucleic acid sequence and employed to evaluate the sequence. Aspects of the invention further include computer programming and systems that include the same which are configured to evaluate candidate CGH probe nucleic acid sequences using a proximity score.

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.

Abstract: Methods and systems for identifying and selecting nucleic acid probes for detecting a target with a nucleic acid probe array or comparative genome hybridization microarray, comprising selecting a plurality of potential target sequences, generating a plurality of candidate probes from the target sequences, filtering the plurality of candidate probes by analyzing candidate probes for selected probe properties in silico. Microarrays comprising probes selected by the methods of the invention are particularly useful for comparative genome hybridization and location analysis.

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: An array-based method for performing SNP analysis is provided. In certain embodiments, the method may comprise: a) contacting a labeled genomic sample with an array comprising a first SNP-detecting oligonucleotide and a second SNP-detecting oligonucleotide that differ from each other by a single nucleotide, under hybridization conditions that provide binding equilibrium; and b) evaluating a SNP of said labeled genomic sample by comparing: i. binding of the labeled genomic sample to the first SNP-detecting oligonucleotide and ii. binding of the labeled genomic sample to said second SNP-detecting oligonucleotide.

Abstract: Methods of evaluating candidate CGH probe nucleic acid sequences are provided. Aspects of the methods include providing a candidate CGH probe nucleic acid sequence for a target sequence of a copy number variation (CNV) of a genome. A proximity score is then determined for the candidate CGH probe nucleic acid sequence and employed to evaluate the sequence. Aspects of the invention further include computer programming and systems that include the same which are configured to evaluate candidate CGH probe nucleic acid sequences using a proximity score.

Abstract: Aspects of the invention include methods of systems of pairwise filtering candidate probe nucleic acid sequences. Aspects of the invention further include methods and systems of selecting candidate probe nucleic acid sequences from plurality thereof, which methods and systems employ a pairwise elimination ranked record of a plurality of candidate probe nucleic acids for a genomic region of interest.

Abstract: Methods for correcting systematic errors in the measured position of deposited features of a nucleic acid array on a substrate. Systematic errors are modeled by an algorithmic model based on measuring the positions (and possibly other properties) of a subset of the features, and a model is constructed for predicting deviations in feature position from an ideal grid. Deviations arising in the deposition process, the scanning process, or both may be corrected.

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: Methods and reagents are disclosed which provide for more sensitive, more accurate and higher through-put analyses of target nucleic acid sequences. The methods and reagents of the present invention may be generically applied to generally any target nucleic acid sequence and do not require a priori information about the presence, location or identity of mutations in the target nucleic acid sequence. The reagents of the invention are mixtures of oligonucleotide precursors having a high level of coverage and mass number complexity, and also having tags analyzable by mass spectrometry which are covalently linked to the precursors through cleavable bonds. A method is also disclosed for analyzing a target nucleic acid sequence employing the mixtures of oligonucleotide precursors having tags analyzable by mass spectrometry covalently linked to the oligonucleotide precursors through cleavable bonds, and chemical or enzymatic assays to alter the mass of the oligonucleotide precursors prior to mass spectral analysis.

Abstract: A method for evaluating an orientation of a molecular array having features arranged in a pattern. An image of the molecular array is obtained by scanning the molecular array to determine data signals emanating from discrete positions on a surface of the molecular array. An actual result of a function on pixels of the image which pixels lie in a second pattern, is calculated. This actual result is compared with an expected result which would be obtained if the second pattern had a predetermined orientation on the array. Array orientation can then be evaluated based on the result.

Abstract: Methods and compositions for performing array-based assays of a nucleic acid sample, such as genomic sample assays, e.g., comparative genomic (aCGH) assays, are provided. Aspects of the invention include arrays containing split-probe nucleic acids that include two linked domains that flank a nucleic acid region, such as a genomic region, of interest. The subject methods and compositions find use in a number of applications, including aCGH applications, e.g., identifying genomic copy number, evaluating the methylation status, etc. Also provided are kits that include the subject arrays.

Abstract: The present invention generally relates to systems and methods for identifying and/or quantifying targets such as nucleic acid targets using compound probes (e.g., oligonucleotide probes), which can comprise first and second sequences able to hybridize to one or more nucleic acids or portions thereof. In one aspect, a nucleic acid (e.g., one or more genomes or chromosomes) may be fragmented, and the fragments exposed to a compound probe. By suitably labeling of the fragments, the amount of binding of each of the fragments to the compound probe may be determined. In some cases, the fragments may be distinguishably labeled, and in certain embodiments, the fragments may be sorted (e.g., via size or charge) prior to exposure to the compound probe.

Abstract: A method of processing one or more detected signal images each acquired from a field of view of a chemical array reader. A location correction is determined based on different detected signals at different image regions which represent regions in the field of view having the same actual signal. Alternatively or additionally, a location correction is applied to a detected signal at an image region. The location correction reduces detected signal discrepancy between different regions in an acquired image which represent different regions in the field of view having the same actual signal. An array reading system and computer program products are also provided.

Abstract: A method and apparatus of interrogating an addressable array unit, which includes a substrate, a light reflecting layer on a front side of the substrate, and a plurality of features on a front side of the array. The method may include, for each of multiple features, illuminating the feature simultaneously with reflected and non-reflected interrogating light. A light emitted from respective features is detected. Either or both, constructive interference of interrogating light at the features, or constructive interference of light emitted from the features, can be obtained to allow lowering of light power from the source, enhanced signal, or reduced noise, or combinations of the foregoing. High depth discrimination may also be obtained without the need for a confocal detection system with conventional pinhole.