Multiplex locus specific amplification
Granted: November 27, 2008
Application Number:
20080293589
Methods are provided for amplifying a plurality of pre-selected target sequences from a complex background of nucleic acids. The targets are selected for amplification using splint oligonucleotides that are used to modify the ends of the fragments. The fragments have known end sequences and the splints are designed to be complementary to the ends. In one aspect the splint brings the ends of the fragment together and the ends are joined to form a circle. In another aspect the splint is…
SYSTEM, METHOD, AND COMPUTER SOFTWARE PRODUCT FOR GENOTYPE DETERMINATION USING PROBE ARRAY DATA
Granted: November 20, 2008
Application Number:
20080287308
An embodiment of a method of analyzing data from processed images of biological probe arrays is described that comprises receiving a plurality of files comprising a plurality of intensity values associated with a probe on a biological probe array; normalizing the intensity values in each of the data files; determining an initial assignment for a plurality of genotypes using one or more of the intensity values from each file for each assignment; estimating a distribution of cluster…
Nucleic Acid Labeling Compounds
Granted: November 20, 2008
Application Number:
20080287667
Nucleic acid labeling compounds are disclosed. The compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofaranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.
Methods for Analyzing Global Regulation of Coding and Non-Coding RNA Transcripts Involving Low Molecular Weight RNAs
Granted: October 23, 2008
Application Number:
20080261817
In some embodiments of the invention, methods are provided to interrogate the transcriptional activity relating to RNAs of small molecular weight. The methods employ hybridization of a large number of oligonucleotide probes with nucleic acid derived from RNAs of small molecular weight.
Analysis of methylation using selective adaptor ligation
Granted: October 16, 2008
Application Number:
20080254453
Methods of analyzing DNA to identify regions of the genome that are methylated in a genomic sample are disclosed. In one aspect genomic DNA is fragmented using a restriction enzyme with a degenerate recognition site, methylated restriction fragments are separated from unmethylated fragments by affinity purification. The complexity of the methylated fragments is reduced by amplification of a subset of the fragments using adaptors that ligate to a subset of the fragments. The amplified…
Feature Intensity Reconstruction of Biological Probe Array
Granted: September 25, 2008
Application Number:
20080232657
The invention provides methods and systems for reconstructing feature intensities from pixel level data. In certain embodiments, the invention uses an empirically determined transfer function to construct a theoretical estimate of pixel level data and then iteratively updates feature intensities based on a minimum multiplicative error between the pixel level data and the theoretical estimate of the pixel level data.
Methods and Kits for Multiplex Hybridization Assays
Granted: August 28, 2008
Application Number:
20080206779
The invention provides a method for genotyping interfering polymorphic loci in a target polynucleotide, such as a strand of genomic DNA, in a multiplex hybridization-based assay. The invention also provides nucleic acid standards for validating the performance of such hybridization-based assays. In one aspect, the method of the invention is carried out by providing for each interfering polymorphic locus one or more probes so that at least one probe is capable of forming a perfectly match…
Multiplex targeted amplification using flap nuclease
Granted: August 21, 2008
Application Number:
20080199916
Methods for multiplex amplification of a plurality of targets of distinct sequence from a complex mixture are disclosed. In one aspect targets are circularized using a single circularization probe that is complementary to two regions in the target that flank a region to be amplified. The targets may hybridize to the circularization probe so that 5? or 3? flaps are generated and methods for removing flaps and circularizing the resulting product are disclosed. In another aspect targets are…
LABEL FREE ANALYSIS OF NUCLEIC ACIDS
Granted: June 19, 2008
Application Number:
20080146454
A method is provided for label free analysis of nucleic acid materials. In accordance with the present invention, a fluorescent material is provided having a certain fluorescence emission without nucleic acids attached thereto. The fluorescent material of the present invention, has a greater emission upon the binding of a single stranded nucleic acid and an even greater emission upon the binding of a double stranded nucleic acid allowing detection of double stranded binding without using…
Enzymatic methods for genotyping on arrays
Granted: June 5, 2008
Application Number:
20080131894
The invention relates to methods for enzymatic, genotyping of polymorphisms on solid supports. In some aspects the methods include ligation of allele or base specific interrogation probes to an array probe. The array probe is labeled by ligation of the interrogation probe. Ligation is dependent on the identity of the base immediately adjacent to the end of the array probe. In other aspects array bound probes are labeled by template dependent extension.
ANTIREFLECTIVE COATINGS FOR HIGH-RESOLUTION PHOTOLITHOGRAPHIC SYNTHESIS OF DNA ARRAYS
Granted: May 22, 2008
Application Number:
20080119371
The present invention provides an array of polymers and methods of forming arrays of polymers by providing a substrate having a first layer including one or more dielectric coatings on a solid support and a second layer including a plurality of polymers disposed on the first layer. The invention also provides methods for forming an array of polymers on a substrate using light-directed synthesis by providing a substrate having a first layer including one or more dielectric coatings on a…
Methods of Analysis of Methylation
Granted: May 8, 2008
Application Number:
20080108073
Methods for determining the methylation status of a plurality of cytosines are disclosed. In some aspects genomic DNA target sequences containing CpGs are targeted for analysis by multiplex amplification using target specific probes that can be specifically degraded prior to amplification. The targets may be modified with bisulfite prior to amplification. In another aspect targets are cut with methylation sensitive or insensitive restriction enzymes and marked with a tag using the target…
Methods, Systems and Computer Software For Designing and Synthesizing Sequence Arrays
Granted: April 24, 2008
Application Number:
20080096771
Embodiments of the invention provides methods, computer software products and systems for arranging polymers during combinatorial polymer synthesis so that the border or edge between synthesis site is minimized. In one embodiment, travelling salesman algorithm is used to minimize the edges. In another embodiment, a locally greedy optimization method is provided. In addition, methods and software products are provided for solving the robust arrangement problem for multi-probe gene…
Complexity Management of Genomic DNA
Granted: March 20, 2008
Application Number:
20080070796
The presently claimed invention provides for novel methods and kits for analyzing a collection of target sequences in a nucleic acid sample. A sample is amplified under conditions that enrich for a subset of fragments that includes a collection of target sequences. The invention further provides for analysis of the above sample by hybridization to an array, which may be specifically designed to interrogate the collection of target sequences for particular characteristics, such as, for…
Methods for high specificity whole genome amplification and hybridization
Granted: March 6, 2008
Application Number:
20080057499
Methods for amplifying genomic DNA using semi-random primers that consist of different combinations of two non-complementary bases are disclosed. In a preferred aspect all of the primers in the collection are composed entirely of the same two non-complementary bases. In preferred aspects the DNA is amplified using R6, Y6, M6 and K6. The amplification is by a strand displacing polymerase and the amplification product may be hybridized to a high complexity array of probes without further…
Polymorphism Detection
Granted: February 21, 2008
Application Number:
20080044920
The present invention generally provides a rapid efficient method for analyzing polymorphic or biallelic markers, and arrays for carrying out these analyses. In general, the methods of the present invention employ arrays of oligonucleotide probes that are complementary to target nucleic acids which correspond to the marker sequences of an individual. The probes are typically arranged in detection blocks, each block being capable of discriminating the three genotypes for a given marker,…
System and Method for Biological Assay
Granted: February 14, 2008
Application Number:
20080038713
The present invention generally relates to microfluidic devices for carrying out and controlling chemical reactions and analysis. In particular, the present invention provides systems, method, and devices related to lab cards.
Instrument to Pneumatically Control Lab Cards and Method Thereof
Granted: February 14, 2008
Application Number:
20080038714
The present invention generally relates to microfluidic devices for carrying out and controlling chemical reactions and analysis. In particular, the present invention provides systems, methods, and devices for controlling lab cards.
Tag Nucleic Acids and Probe Arrays
Granted: February 7, 2008
Application Number:
20080032408
The invention provides a unique set of nucleic acid sequences which is appropriate for use for a wide variety of applications requiring nucleic acid tags. As such, the sequence tags of the presently claimed invention may be used, for example, to label biological and nonbiological materials, in genotyping applications and in a variety of other analyses.
SYSTEM, METHOD, AND PRODUCT FOR GENERATING PATTERNED ILLUMINATION
Granted: January 24, 2008
Application Number:
20080020938
An embodiment of a method for generating an interference pattern at a probe array is described that comprises directing light at a first waveguide and second waveguide, wherein the first and second waveguides are positioned adjacent to each other and the output from the first and second waveguides produce an interference pattern; and directing the interference pattern at the probe array.
