Affymetrix, Inc.

Other

Verinata Health, Inc.

Genisphere, LLC

Affymetix, Inc.

Keith W Jones

Michael H Shapero

Jing Huang

Glenn K Fu

Ronald J Sapolsky

Yuker Wang

Stephen P A Fodor

Richard P Rava

Darya Chudova

David A Comstock

Catalin Barbacioru

Radharani Duttagupta

Earl A Hubbell

Robert J Lipshutz

Andrew Sparks

Robert C Getts

Gengxin Chen

Dimitri Skvortsov

Sven Duenwald

Rui Mei

Simon Cawley

Hajime Matsuzaki

Teresa A Webster

August Estabrook

Xiaojun Di

Gregory Marcus

Thomas D Stamato

Weiwei Liu

Rong Jiang

Jeremy N Gollub

Lawrence Greenfield

John Efcavitch

Laurent Bellon

Darya I Chudova

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 5' 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.

Enzymatic methods for genotyping on arrays

Disclosed are methods for determining copy number variation (CNV) known or suspected to be associated with a variety of medical conditions. In some embodiments, methods are provided for determining copy number variation of fetuses using maternal samples comprising maternal and fetal cell free DNA. In some embodiments, methods are provided for determining CNVs known or suspected to be associated with a variety of medical conditions. Some embodiments disclosed herein provide methods to improve the sensitivity and/or specificity of sequence data analysis by deriving a fragment size parameter. In some implementations, information from fragments of different sizes are used to evaluate copy number variations. In some implementations, one or more t-statistics obtained from coverage information of the sequence of interest is used to evaluate copy number variations. In some implementations, one or more fetal fraction estimates are combined with one or more t-statistics to determine copy number variations.

Using cell-free DNA fragment size to determine copy number variations

Compositions, methods and kits are disclosed for synthesizing and amplifying pools of probes using precursor oligonucleotides. In some aspects the precursor is amplified and nicking enzymes are used to separate the full length probes from the amplification products. The methods enable the preparation of single stranded DNA probes of defined sequence and length that are suitable for use in target detection assays.

Methods for synthesizing pools of probes

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 bases that are identical in each sequence in the plurality of sequences and positions that vary from one locus specific region to another. The sequences are selected based on proximity to a polymorphism of interest and because they conform to a similar sequence pattern.

Methods for genotyping selected polymorphism

Methods of identifying allele-specific 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. The methods may be used to diagnose cancer and other diseases associated with chromosomal anomalies.

Methods for identifying DNA copy number changes

Methods for detecting genomic rearrangements are provided. In one embodiment, methods are provided for the use of paired end tags from restriction fragments to detect genomic rearrangements. Sequences from the ends of the fragments are brought together to form ditags and the ditags are detected. Combinations of ditags are detected by an on-chip sequencing strategy that is described herein, using inosine for de novo sequencing of short segments of DNA. In another aspect, translocations are identified by using target specific capture and analysis of the captured products on a tiling array.

Array-based translocation and rearrangement assays

A drum tuning key includes a body having a longitudinal axis, a first end and a second end, the first end including a keyed interface configured to releaseably engage an element of a tuning assembly of a drum for cooperative rotation therewith and the second end including a radially-extending portion configured to be manipulated by a user to apply a torque in relation to the longitudinal axis to operate the tuning assembly, and a magnet carried by the body and having a first end, a second end, and an axis of magnetization extending between the first end and the second end, wherein at least one of the first end or the second end of the magnet is located at or adjacent an outer surface of the body.

Systems and methods for management of percussion accessories

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.

Methods for diagnosis and surveillance of complex multi-factorial disorders such as cancer by screening of easily accessible biomarkers are disclosed. Highly stable cell free Circulating Nucleic Acids (CNA) present as both RNA and DNA species have been discovered in the blood and plasma of humans. Correlations between tumor-associated genomic/epigenetic/transcriptional changes and alterations in CNA levels are strong predictors of the utility of this biomarker class as clinical indicators. Methods for using microRNAs (miRNAs) representing a class of naturally occurring small non-coding RNAs of 19-25 nt as markers that can associate their specific expression profiles with cancer development are disclosed. Methods for isolating plasma fractions for the study of miRNA biomarkers and for measurement of circulating miRNA levels are disclosed.

Circulating miRNA biomaker signatures

Methods for diagnosing inflammatory bowel disease and ulcerative colitis using miRNA biomarkers for these diseases are provided. Differential expression of the miRNA biomarkers in blood fractions, e.g., platelets, of diseased individuals as compared to expression levels in normal individuals indicates the presence of IBD or ulcerative colitis. Also provided are microarrays for use in the diagnostic methods, wherein the features of the microarray consist essentially of nucleic acid sequences that hybridize to the miRNA biomarkers and normalization controls.

miRNA biomarkers for ulcerative colitis

An adaptor for coupling to a drum having a drum head, shell, and rim, the rim having an outer diameter and configured to interface with a ring coupled to the drum head to hold the drum head in place on the shell, includes a monolithic body having a clip portion and an interface, the clip portion configured to extend around an outer section of the rim between a top surface of the drum head and a bottom portion of the rim, the clip portion having a clip end and the ring having an outer diameter, wherein the clip end is configured to extend to a position that is inward of the outer diameter of the ring when the clip portion is coupled to the drum; and wherein a substantial portion of the interface is configured to extend radially from the rim when the clip portion is coupled to the drum.

Adaptor for drum

Growing community of inventors

Sunnyvale, CA, United States of America

Keith W Jones