California Institute of Technology

Leland Stanford Junior University

University of California

Cz Biohub Sf, Llc.

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Agency for Science, Technology and Research

Fluidigm Corporation

Verinata Health, Inc.

Siemens Medical Solutions Usa, Inc.

The University of North Carolina at Chapel Hill

The University of Chicago

Statens Serum Institut

Helicos Biosciences Corporation

U.S. Government Nih Division of Extramural Inventions and Technology Resources (deitr)

Chan Zuckerberg Biohub, Inc.

Stephen R Quake

Hou-Pu Chou

Todd A Thorsen

Carl L Hansen

Marc Alexander Unger

Axel Scherer

Hei-Mun Christina Fan

Hannah Valantine

James M Berger

Thomas M Snyder

Mark L Adams

Markus M Enzelberger

Jian Liu

Vincent Studer

Michael Kertesz

Emil Paskalev Kartalov

Ning Jiang

Joshua Weinstein

Daniel S Fisher

W French Anderson

Mark Alec Kowarsky

Lance Martin

Wenying Pan

Lian Chye Winston Koh

Yann Gambin

Jianbin Wang

Olivier Legrand

Sebastian J Maerkl

Kiran Kaur Khush

James P Brody

Wayne D Volkmuth

Jared Leadbetter

Jong Wook Hong

Anne Y Fu

Morten Sommer

Iwijn De Vlaminck

Derek Croote

Wayne D Volksmuth

Frederick Balagadde

Kari C Nadeau

Ismail Emre Araci

Markus Enzelberger

Lawrence A Wade

Spyros Darmanis

David N Cornfield

Xiaoyan Bao

Richard P Rava

Frances H Arnold

Michael F Clarke

R Michael Van Dam

David A Comstock

Maximilian Diehn

Manjula Chinnappa

Gabrielle Heilek

Chunxiao Song

Piero D Dalerba

Michael Van Dam

Charles F Spence

Huiping Liu

Chiem Ma

Yosef Mandel

Lewis Z Hong

Guillaume Lessard

Jordan M Gerton

William F Burkholder

Anne A Leyrat

Tomer Kalisky

Dmitry Pushkarev

Ayelet Voskoboynik

Harry A Atwater

Jason P Rolland

Joseph Desimone

James R Heath

Julia A Kornfield

Hartmuth C Kolb

Milan Mrksich

Arkadij M Elizarov

Hsian-Rong Tseng

Antoine Daridon

Shirit Einav

Charles Patrick Collier

Jiang Huang

Melvin I Simon

Michael E Phelps

Paul Wyatt

Neethan A Lobo

Ian R Shapiro

Nate Cira

Joshua S Marcus

Michael Robles

Jason Khoo

Mark A Unger

Derek A Schorzman

Jason Yarbrough

Chung-cheng Lee

Iwijn De Vlaminick

Guodong Sui

Shulamit Eyal

Ido Braslavsky

Melanie Hayden Gephart

The present invention provides an approach to increase the effective read length of commercially available sequencing platforms to several kilobases and be broadly applied to obtain long sequence reads from mixed template populations. A method for generating extended sequence reads of long DNA molecules in a sample, comprising the steps of assigning a specific barcode sequence to each template DNA molecule in a sample to obtain barcode-tagged molecules: amplifying the barcode-tagged molecules; fragmenting the amplified barcode-tagged molecules to obtain barcode-containing fragments; juxtaposing the barcode-containing fragments to random short segments of the original DNA template molecule during the process of generating a sequencing library to obtain demultiplexed reads; and assembling the demultiplexed reads to obtain extended sequence reads for each DNA template molecule, is disclosed.

Method for generating extended sequence reads

The invention is directed to methods of identifying woman is risk for preterm delivery. In some aspects, the methods include quantitating one or more placental or fetal-tissue specific genes in a biological sample from the woman.

Noninvasive molecular clock for fetal development predicts gestational age and preterm delivery

Provided herein is a method for analyzing genomic DNA In some embodiments, the method may comprise labeling a genomic sample by adding a capture tag to the ends of the DNA molecules in the sample and labeling molecules that comprise hydroxymethylcytosine with a first fluorophore, immobilizing the labeled DNA molecules on a support, and imaging individual molecules of hydroxymethylated genomic DNA on the support.

Simultaneous single-molecule epigenetic imaging of DNA methylation and hydroxymethylation

The invention generally relates to methods for assessing the health of a tissue by characterizing circulating nucleic acids in a biological sample. According to certain embodiments, methods for assessing the health of a tissue include the steps of detecting a sample level of RNA in a biological sample, comparing the sample level of RNA to a reference level of RNA specific to the tissue, determining whether a difference exists between the sample level and the reference level, and characterizing the tissue as abnormal if a difference is detected.

Methods for profiling and quantitating cell-free RNA

Methods, devices, compositions and kits are provided for analysis of the microbiome or individual components thereof in an individual. The methods find use in a determination of infection, in analysis of the microbiome structure, in determining the immunocompetence of an individual, and the like. In some embodiments of the invention, the individual is treated with an therapeutic regimen, e.g. drugs, diet, radiation therapy, and the like.

Cell-free nucleic acids for the analysis of the human microbiome and components thereof

Provided are antibodies or antigen binding portions thereof that specifically bind Dengue virus, various compositions of such antibodies or antigen binding portions thereof, and methods of their use. Provided are such antibodies, fragments of such antibodies retaining Dengue virus-binding ability, pharmaceutical compositions including such antibodies or antigen binding fragments thereof, and diagnostic compositions including such antibodies or antigen binding fragments thereof. Also provided are isolated nucleic acids encoding such antibodies, amino acid sequences of such antibodies, and host cells transformed therewith. Additionally, provided are prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the disclosure.

Antibodies against dengue virus and related methods

In one aspect, methods of generating human monoclonal antibodies that specifically binds to an allergen are provided. In some embodiments, the monoclonal antibodies are generated from sequences identified from isolated single B cells from a human subject who is allergic to the allergen.

Methods of isolating allergen-specific antibodies from humans and uses thereof

Disclosed is a method to achieve digital quantification of DNA (i.e., counting differences between identical sequences) using direct shotgun sequencing followed by mapping to the chromosome of origin and enumeration of fragments per chromosome. The preferred method uses massively parallel sequencing, which can produce tens of millions of short sequence tags in a single run and enabling a sampling that can be statistically evaluated. By counting the number of sequence tags mapped to a predefined window in each chromosome, the over- or under-representation of any chromosome in maternal plasma DNA contributed by an aneuploid fetus can be detected. This method does not require the differentiation of fetal versus maternal DNA. The median count of autosomal values is used as a normalization constant to account for differences in total number of sequence tags is used for comparison between samples and between chromosomes.

Noninvasive diagnosis of fetal aneuploidy by sequencing

The invention provides compositions and methods for simultaneously determining the presence or absence of fetal aneuploidy and the relative amount of fetal nucleic acids in a sample obtained from a pregnant female. The method encompasses the use of sequencing technologies and exploits the occurrence of polymorphisms to provide a streamlined noninvasive process applicable to the practice of prenatal diagnostics.

Simultaneous determination of aneuploidy and fetal fraction

The present invention provides an approach to increase the effective read length of commercially available sequencing platforms to several kilobases and be broadly applied to obtain long sequence reads from mixed template populations. A method for generating extended sequence reads of long DNA molecules in a sample, comprising the steps of: assigning a specific barcode sequence to each template DNA molecule in a sample to obtain barcode-tagged molecules; amplifying the barcode-tagged molecules to obtain barcode-containing fragments; juxtaposing the barcode-containing fragments to random short segments of the original DNA template molecule during the process of generating a sequencing library to obtain demultiplexed reads; and assembling the demultiplexed reads to obtain extended sequence reads for each DNA template molecule, is disclosed.

The present methods are exemplified by a process in which maternal blood containing fetal DNA is diluted to a nominal value of approximately 0.5 genome equivalent of DNA per reaction sample. Digital analysis is then be used to detect aneuploidy, such as the trisomy that causes Down Syndrome. Since aneuploidies do not present a mutational change in sequence, and are merely a change in the number of chromosomes, it has not been possible to detect them in a fetus without resorting to invasive techniques such as amniocentesis or chorionic villi sampling. Digital amplification allows the detection of aneuploidy using massively parallel amplification and detection methods, examining, e.g., 10,000 genome equivalents.

Non-invasive fetal genetic screening by digital analysis

Identifying human B cells expressing anti-allergen antibodies

The invention provides methods, devices, compositions and kits for diagnosing or predicting transplant status or outcome in a subject who has received a transplant.

Non-invasive diagnosis of graft rejection in organ transplant patients

Allergen-specific antibodies

Growing community of inventors

Stanford, CA, United States of America

Stephen R Quake