William Marsh Rice University

Harvard College

Mount Sinai School of Medicine

Other

California Institute of Technology

David Y Zhang

Peng Yin

Margaret Brandwein

Juexiao Wang

Erik Winfree

Ruojia Wu

Wei Sun

Thomas E Schaus

Terence C H Hsuih

Fred Russell Kramer

Bernard Yurke

Xi Chen

Ying Jie Wu

Wei Duan

Francis Manzella

Alexander B Chetverin

Robert A Diamond

Andrew J Turberfield

Jizu Yi

Alexander S Spirin

Terence C Hsuih

Frank Vollmer

David Soloveichik

Yuqiang Wu

Wandi Zhang

Xuemeng Zhang

Viktor I Ugarov

Zheng Fang

John G Kirchner

Yan Yan

Ping Song

Georg Seelig

Alessandro Pinto

Oleg V Kurnasov

Lyubov A Ryabova

Igor Y Morosov

Elena V Volianik

Provided herein are reagents and methods for simultaneously enriching many potential rare genetic variants at different genetic loci. The rare variants enriched can include single nucleotide polymorphisms (SNPs), single nucleotide variants, or small insertions and deletions. Embodiments of the invention include procedures for integration with downstream next generation sequencing (NGS) analysis. Embodiments of the invention include analysis of nonpathogenic SNPs for the determination of cell identity and detection of cell contamination using qPCR or NGS.

Systems and methods for allele enrichment using multiplexed blocker displacement amplification

Provided herein are primers and primer systems having improved specificity and kinetics over existing primers, and methods of use thereof.

Compositions of toehold primer duplexes and methods of use

This invention describes a method of controlling the hybridization yield of nucleic acid probes by adjusting the relative concentrations of auxiliary oligonucleotides to the probes and the targets. The auxiliary oligonucleotide is partially or fully complementary to either the probe or the target, and is released upon hybridization of the probe to the target.

Stoichiometric tuning of nucleic acid hybridization probes by auxiliary oligonucleotide species

This present disclosure describes hybridization probes modularly constructed from several oligonucleotides with a pattern of designed complementary interactions, allowing the probes to sequence-specifically capture or analyze nucleic acid target sequences that are long and/or complex.

Molecular hybridization probes for complex sequence capture and analysis

Embodiments of methods, systems, and tangible non-transitory computer readable medium having instructions are presented. A method includes calculating a plurality of feature values for a number of bioinformatic features of the desired hybridization reaction; and calculating distances between the plurality of feature values and corresponding database rate constant values stored in a database, the database comprising a plurality of hybridization reactions having known rate constants. The method additionally includes calculating a weighted average of a logarithm of the database rate constant values, with larger weights assigned to value instances having values lower in distance to the plurality of feature values of the desired hybridization reaction; and providing the weighted average as a predicted logarithm of the rate constant of the desired hybridization reaction.

Method, apparatus, and computer-readable medium for predicting a hybridization rate constant of a first sequence

This disclosure describes a method of purifying several full-length oligonucleotide targets from corresponding synthesis truncation products, in a way that ensures roughly stoichiometric equality among the targets.

Stoichiometric nucleic acid purification using randomer capture probe libraries

The present disclosure describes the thermodynamic design and concentrations necessary to design probe compositions with desired optimal specificity that enable enrichment, detection, quantitation, purification, imaging, and amplification of rare-allele-bearing species of nucleic acids (prevalence &#x3c;1%) in a large stoichiometric excess of a dominant-allele-bearing species (wildtype). Being an enzyme-free and homogeneous nucleic acid enrichment composition, this technology is broadly compatible with nearly all nucleic acid-based biotechnology, including plate reader and fluorimeter readout of nucleic acids, microarrays, PCR and other enzymatic amplification reactions, fluorescence barcoding, nanoparticle-based purification and quantitation, and in situ hybridization imaging technologies.

Competitive compositions of nucleic acid molecules for enrichment of rare-allele-bearing species

Compositions and methods for highly specific nucleic acid probes and primers are provided. The probe system comprises a complement strand and a protector stand that form a partially double-stranded probe. The reaction standard free energy of hybridization between the probe and target nucleic acid as determined by Expression 1 (&#x394;G&#xb0;=&#x394;G&#xb0;&#x2212;&#x394;G&#xb0;+(&#x394;G&#xb0;&#x2212;&#x394;G&#xb0;)) is from about &#x2212;4 kcal/mol to about +4 kcal/mol. Alternatively, the reaction standard free energy of hybridization between the probe and target nucleic acid is determined by Expression 1 to be within 5 kcal/mol of the standard free energy as determined by Expression 2 (&#x2212;R&#x3c4; ln(([P]&#x2212;[C])/[C])]), where the [P]term of Expression 2 equals the concentration of the protector strand and the [C]term of Expression 2 equals the concentration of the complement strand. In addition, a method for on-the-fly fine tuning of a reaction using the present probe is provided.

Fine-tuned ultraspecific nucleic acid hybridization probes

The present disclosure provides, in various aspects and embodiments, methods and compositions for selectively amplifying a rare target nucleic acid and/or suppressing amplification of non-target nucleic acids with sequences similar to the rare target nucleic acid. The methods and composition are useful, for example, for detecting rare alleles among a population of wild-type alleles.

Specific nucleic acid amplification with compounded selectivity

The invention provides systems and methods for spatial sequestration of elements in nucleic acid circuits.

Spatial sequestration of dynamic nucleic acid circuits

The invention provides compositions and methods relating to self-assembly of structures of various size and shape complexity. The composition include synthetic single-stranded polymers having a backbone and pre-determined linear arrangement of monomers.

Compositions and methods for self-assembly of polymers with complementary macroscopic and microscopic scale units

A sensor device, which is adapted for detecting target molecules having a target nucleic acid sequence, comprises an optical whispering gallery mode (WGM) resonator having a resonance frequency, wherein the WGM resonator is functionalized with a double-strand DNA precursor compound and the resonance frequency depends on a mass load provided by the double-strand precursor compound, the double-strand precursor compound is capable of a target-specific strand displacement reaction with the target molecules, and in response to the strand displacement reaction, the double-strand precursor compound is capable to be partially decoupled from the WGM resonator, wherein the mass load can be decreased and the resonance frequency of the WGM resonator can be increased. Furthermore, a sensing method for detecting target molecules including nucleic acid sequences is described.

Sensor device and method for label-free detecting of nucleic acid sequences

A window or door is constructed to accept one or more intermediate pieces which may be used for adjusting the depth of the window or door. The intermediate piece includes, on one side, a first hook and an outrigger, and on the other side, a second hook and structure defining an outrigger receiving slot. The intermediate pieces lockingly and securely mate with the interior and exterior sections of the windows or doors.

Intermediate member for extending the depth of a window or door and window or door constructed with same

Growing community of inventors

Jamaica, NY, United States of America

David Y Zhang