Element Biosciences, Inc.

Illumina Corporation

Life Technologies Corporation

University System of Maryland

Illumina Singapore Pte. Ltd.

Michael Previte

Molly Min He

Matthew William Kellinger

Cheng-Yao Chen

Chunhong Zhou

Sinan Arslan

Junhua Zhao

Theo Nikiforov

Guobin Luo

Minghao Guo

Steve Xiangling Chen

Mostafa Ronaghi

Rigo Pantoja

Derek Fuller

William Light

Barnett B Rosenblum

Peter B Vander Horn

Eric T Kool

Marian Peris

Hongye Sun

Michael Phelan

Yufang Wang

Zhaohui Zhou

Samantha Snow

Jamshid Temirov

Stefanie Yukiko Nishimura

Hongyi Wang

Lei Sun

Sergio Peisajovich

Hua Yu

Misha Golynskiy

Joseph M Beechem

Erin Bomati

Vi-En Choong

Xinzhan Peng

Yu-Hsien Hwang-Fu

Michael Kim

Hui Zhen Mah

Marco Tjioe

Andrew Boddicker

Adeline Huizhen Mah

M Shane Bowen

Chris D Geddes

Lorenzo Berti

Saurabh Nirantar

Tyler Lopez

Seth McDonald

BeiBei Wang

Jake Levieux

Su Zhang

Leon Zilun Zhang

Jonathan Mark Boutell

Arash Ghorbani

Michael Klein

Virginia Saade

Mark Ambroso

Shane Bowen

Ramreddy Tippana

Russell Hudyma

John Bailey

Hui Zhen Ma

Steven Xiangling Chen

A method for synthesizing a nucleic acid includes synthesizing one or more nucleic acid fragments on a substrate. The synthesized one or more nucleic acid fragments may be amplified on the substrate. The method also includes sequencing the synthesized or amplified one or more nucleic acid fragments on the substrate. The sequencing may provide feedback to designs of the one or more nucleic acid fragments. The method further includes harvesting the synthesized or amplified one or more nucleic acid fragments based on sequencing. The synthesized or amplified one or more nucleic acid fragments may be assembled to generate a target nucleic acid.

Nucleic acid synthesis techniques

Compositions and methods comprising the use of polymerase-nucleotide conjugates for nucleic acid sequencing and analysis applications are described.

Polymerase-nucleotide conjugates for sequencing by trapping

Multivalent binding compositions including a particle-nucleotide conjugate having a plurality of copies of a nucleotide attached to the particle are described. The multivalent binding compositions allow one to localize detectable signals to active regions of biochemical interaction, e.g., sites of protein-protein interaction, protein-nucleic acid interaction, nucleic acid hybridization, or enzymatic reaction, and can be used to identify sites of base incorporation in elongating nucleic acid chains during polymerase reactions and to provide improved base discrimination for sequencing and array based applications.

Multipart reagents having increased avidity for polymerase binding

Multivalent binding composition for nucleic acid analysis

This disclosure provides a method of determining a sequence of nucleotides for a nucleic acid template. The method can include the steps of contacting the nucleic acid template with a conformationally labeled polymerase and at least four different nucleotide species under conditions wherein the conformationally labeled polymerase catalyzes sequential addition of the nucleotide species to form a nucleic acid complement of the nucleic acid template, wherein the sequential addition of each different nucleotide species produces a conformational signal change from the conformationally labeled polymerase and wherein the rate or time duration for the conformational signal change is distinguishable for each different nucleotide species; detecting a series of changes in the signal from the conformationally labeled polymerase under the conditions; and determining the rates or time durations for the changes in the signal, thereby determining the sequence of nucleotides for the nucleic acid template.

Conformational probes and methods for sequencing nucleic acids

Provided herein are compositions and systems for use in polymerase-dependent, nucleotide transient-binding methods. The methods are useful for deducing the sequence of a template nucleic acid molecule and single nucleotide polymorphism (SNP) analyses. The methods rely on the fact that the polymerase transient-binding time for a complementary nucleotide is longer compared to that of a non-complementary nucleotide. The labeled nucleotides transiently-binds the polymerase in a template-dependent manner, but does not incorporate. The methods are conducted under any reaction condition that permits transient binding of a complementary or non-complementary nucleotide to a polymerase, and inhibits nucleotide incorporation.

Nucleotide transient binding for sequencing methods

Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the fields-of-view, improved imaging system duty cycle and a more compact system, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications at a lower cost.

Optical systems for nucleic acid sequencing and methods thereof

Provided herein are methods for generating circular nucleic acid molecules and circular nucleic acid libraries. The methods can be used to generate clonal populations of target nucleic acid molecules for downstream applications such as sequencing.

Methods for generating circular nucleic acid molecules

The present disclosure provides compositions and methods that employ the compositions for conducting pairwise sequencing and for generating concatemer template molecules for pairwise sequencing. The concatemers can be generated using a rolling circle amplification reaction which is conducted either on-support, or conducted in-solution and then distributed onto a support. The rolling circle amplification reaction generates concatemers containing tandem copies of a sequence of interest and at least one universal adaptor sequence. An increase in the number of tandem copies in a given concatemer increases the number of sites along the concatemer for hybridizing to multiple sequencing primers which serve as multiple initiation sites for polymerase-catalyzed sequencing reactions. When the sequencing reaction employs detectably labeled nucleotides and/or detectably labeled multivalent molecules (e.g., having nucleotide units), the signals emitted by the nucleotides or nucleotide units that participate in the parallel sequencing reactions along the concatemer yields an increased signal intensity for each concatemer.

Compositions and methods for pairwise sequencing

Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the sample plane to capture a series of images (e.g., of different fields-of-view), and improved imaging system duty cycle, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications.

High performance fluorescence imaging module for genomic testing assay

A method of characterizing candidate agents including steps of (a) providing a library of candidate agents attached to nucleic acid tags; (b) contacting the library with a solid support to attach the candidate agents to the solid support, whereby an array of candidate agents is formed; (c) contacting the array with a screening agent, wherein one or more candidate agents in the array react with the screening agent; (d) detecting the array to determine that at least one candidate agent in the array reacts with the screening agent; (e) sequencing the nucleic acid tag to determine the tag sequences attached to candidate agents in the array; and (f) identifying the at least one candidate agent in the array that reacts with the screening agent based on the tag sequence that is attached to the at least one candidate agent.

Platform for discovery and analysis of therapeutic agents

Provided herein are fluorescently-labeled nucleotide conjugates for nucleic acid analysis. Also provided are reagents used for forming binding complexes between a fluorescently-labeled nucleotide conjugate and a target nucleic acid sequence in the presence of one or more reagents disclosed herein. Binding complexes can be detected in the presence of the one or more reagents. For example, the one or more reagents may contain a photobleaching reducing agent configured to reduce photobleaching resulting from use of the fluorescently-labeled nucleotide conjugate to form the binding complex in a nucleic acid analysis. Such nucleic acid analysis may be used to identify sites of nucleobase binding or incorporation between the target nucleic acid sequence and one or more nucleotide moieties of the fluorescently-labeled nucleotide conjugate in a nucleic acid sequence reaction.

Methods and reagents for nucleic acid analysis

Growing community of inventors

San Diego, CA, United States of America

Michael Previte