Methods and computer software products for designing nucleic acid arrays
Granted: July 21, 2005
Application Number:
20050158790
Methods and computer software products are provided for selecting nucleic acid probes. In one embodiment, perfect match intensity, mismatch intensity and the slope of quantitative response of a probe are predicted. A unified quality score is calculated. Probes are selected based on the unified quality score.
Bioarray chip reaction apparatus and its manufacture
Granted: July 21, 2005
Application Number:
20050158819
A body 300 having a cavity 310 for mounting a substrate 120 fabricated with probe sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, is provided. The cavity includes inlets 350 and 360 for introducing selected fluids into the cavity to contact the probes. Accordingly, a commercially feasible device for use in high throughput assay systems is provided.
Nucleic acid analysis techniques
Granted: July 21, 2005
Application Number:
20050158772
The present invention provides a simplified method for identifying differences in nucleic acid abundances (e.g., expression levels) between two or more samples. The methods involve providing an array containing a large number (e.g. greater than 1,000) of arbitrarily selected different oligonucleotide probes where the sequence and location of each different probe is known. Nucleic acid samples (e.g. mRNA) from two or more samples are hybridized to the probe arrays and the pattern of…
Analysis of methylation status using oligonucleotide arrays
Granted: July 14, 2005
Application Number:
20050153347
The present invention provides for novel methods and kits for determining the methylation status of a cytosine in a nucleic acid sample. The methylation status of a plurality of cytosines may be determined simultaneously. In one embodiment methylation status is determined using methylation specific modification of cytosines followed by locus specific amplification, single base extension at the interrogation position and identification of the extended base by array hybridization. In…
Sequence of surface immobilized polymers utilizing microfluorescence detection
Granted: July 7, 2005
Application Number:
20050148002
Means for simultaneous parallel sequence analysis of a large number of biological polymer macromolecules. Apparatus and methods may use fluorescent labels in repetitive chemistry to determine terminal manomers on solid phase immobilized polymers. Reagents which specifically recognize terminal manomers are used to label polymers at defined positions on a solid substrate.
Very large scale immobilized polymer synthesis
Granted: July 7, 2005
Application Number:
20050148027
A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection…
Methods for genotyping selected polymorphism
Granted: June 30, 2005
Application Number:
20050142577
Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some…
System, method, and product for mixing fluids in a chamber
Granted: June 30, 2005
Application Number:
20050142664
In one embodiment a method of mixing fluid is described that comprises providing a vibration comprising a resonant frequency; sympathetically amplifying the vibration in response to the resonant frequency; and modulating the resonant frequency, to cause the amplified vibration to generate turbulent flow in a fluid that influences the likelihood of interaction between a target molecule in the fluid with a probe on a biological probe array.
Light-based detection and manipulation of single molecules
Granted: June 23, 2005
Application Number:
20050136412
In one aspect of the invention, single biological molecules are detected and manipulated using light tweezers. In some embodiments, the biological molecules are selectively moved to detection features for characterization.
Methods for monitoring expression of polymorphic alleles
Granted: June 23, 2005
Application Number:
20050136452
Methods and arrays for monitoring and detecting allele specific expression of multiallelic loci are provided. The methods and arrays may be used for detecting allele specific expression patterns using hybridization to allele specific probes and sets of probes.
Methods and computer software products for identifying transcribed regions of a genome
Granted: June 23, 2005
Application Number:
20050136420
Methods and computer software products are provided for transcriptional annotation. In one embodiment of the invention, a region of the genome where the intensity of hybridization of all the probes are above a threshold value (usually the level of non-specific hybridization) is identified. The region may be identified by aligning the probes against the genome; walking through the genome to find regions where all consecutive probes have intensities above the threshold value.
Amplification of nucleic acids
Granted: June 23, 2005
Application Number:
20050136417
Methods and kits for amplifying nucleic acids are provided. Double stranded cDNA with uridine residues incorporated into one strand is synthesized and the uridine containing strand is nicked at uridine residues. The DNA is extended from the nicks in the presence of dUTP using a strand displacing enzyme. Repeated cycles of nicking and extension result in amplification of the nucleic acid. Methods are also provided for analysis of the above sample by hybridization to an array, which may be…
Methods for genetic analysis of SARS virus
Granted: June 23, 2005
Application Number:
20050136395
The invention provides arrays and probes for resequencing a SARS virus using an array of probes that are complementary to a SARS reference sequence and to each possible single nucleotide substitution of the reference sequence. Methods of identifying mutations in viral sequences and methods of characterizing viral isolates are also provided. The invention also provides high throughput methods to monitor epidemics and pandemics caused by pathogens such as viruses.
Methods, systems and computer software for detecting pixel stutter
Granted: June 23, 2005
Application Number:
20050135702
Embodiments of the invention provide methods, computer software products and systems for detecting pixel stutter of a scanner. In one embodiment, a numeric count of stuttered pixels in both the x (row) and y (column) directions and a graphic display of the stuttered pixels overlaid on the image data are provided by the invention. The y-direction stutter count provides the estimate of pixel stutter from pure statistical data variations.
Methods for identifying DNA copy number changes
Granted: June 16, 2005
Application Number:
20050130217
Methods of identifying changes in genomic DNA copy number are disclosed. Methods for identifying homozygous deletions and genetic amplifications are disclosed. An array of probes designed to detect presence or absence of a plurality of different sequences is also disclosed. The probes are designed to hybridize to sequences that are predicted to be present in a reduced complexity sample. The methods may be used to detect copy number changes in cancerous tissue compared to normal tissue.…
Methods for making a device for concurrently processing multiple biological chip assays
Granted: June 9, 2005
Application Number:
20050123907
Methods for concurrently processing multiple biological chip assays by providing a biological chip plate comprising a plurality of test wells, each test well having a biological chip having a molecular probe array; introducing samples into the test wells; subjecting the biological chip plate to manipulation by a fluid handling device that automatically performs steps to carry out reactions between target molecules in the samples and probes; and subjecting the biological chip plate to a…
Methods of small sample amplification
Granted: June 9, 2005
Application Number:
20050123943
The present invention relates to the amplification of nucleic acids, preferably from mRNA. A primer and promoter are added to a target sequence to be amplified and then the target is amplified in an in vitro transcription reaction and the product of this reaction is used as template for subsequent rounds of amplification.
Methods for modifying DNA for microarray analysis
Granted: June 9, 2005
Application Number:
20050123956
In one aspect of the invention, methods and compositions are provided for fragmenting nucleic acid samples. Fragmented nucleic acid samples may be used for hybridization with microarrays.
System, method, and computer software product for generating genotype calls
Granted: June 9, 2005
Application Number:
20050123971
A method for calling the genotype of a sample is described comprising the acts of receiving emission data for one or more target sequences each hybridized to a plurality of probe sets, where each of the probe sets comprises a plurality of probe features; calculating a set of values for each of the probe sets associated with each target sequence; selecting one of the set of values for each of the probe sets associated with each target sequence, wherein the value is selected if it is…
Method for depleting specific nucleic acids from a mixture
Granted: June 9, 2005
Application Number:
20050123987
The presently claimed invention provides methods, compositions, and apparatus for analyzing nucleic acids isolated from blood. Specifically, the present invention provides a method of analyzing blood samples by blocking amplification of selected unwanted RNAs and subsequently analyzing the amplified sample by hybridization to a plurality of probes attached to a solid support. In one embodiment, the invention provides enriching for a population of interest in a complex population by…
