Method Specially Adapted For Identifying A Library Member Patents (Class 506/2)
  • Patent number: 10337072
    Abstract: Described herein are methods of measuring, in a genomic sample from an individual, the relative frequency of a target sequence (that is, its copy number) with respect to a control sequence of known copy number at a different genomic locus in the same genome, wherein the target and control sequences differ by at least one single nucleotide variation (SNV). These methods involve both the target sequence and the control sequence in a single reaction/container, using a pair of primers that prime amplification of both the target sequence and the control sequence, or a single downstream primer and two upstream primers (that differs only at the position of the SNV between the target and control sequences), and measuring the abundance of each of the target sequence and the control sequence using SNV-specific labeled probes or primers, or a melting curve analysis that distinguishes between the amplified control and target sequences. The methods are exemplified with various different amplifications process.
    Type: Grant
    Filed: January 8, 2016
    Date of Patent: July 2, 2019
    Assignee: The Board of Trustees of the University of Illinois
    Inventors: Matthew E. Hudson, Brian W. Diers, Tong Geon Lee
  • Patent number: 10329605
    Abstract: A method for detecting a low-occurrence mutation in isolated DNA adds a blocking probe to reagents during amplification of the isolated DNA. The blocking probe is an oligonucleotide complementary to wild-type DNA corresponding to the sample. The blocking probe spans a site of a suspected mutation within a region of interest in the isolated DNA. After amplification, fragments of the amplified DNA is sequenced using next generating sequencing and an output is generated to display the sequenced fragments. In some embodiments, the blocking probe is locked nucleic acid (LNA).
    Type: Grant
    Filed: April 20, 2016
    Date of Patent: June 25, 2019
    Assignee: NEOGENOMICS LABORATORIES, INC.
    Inventor: Maher Albitar
  • Patent number: 10323279
    Abstract: This disclosure provides methods and compositions for sample processing, particularly for sequencing applications. Included within this disclosure are bead compositions, such as diverse libraries of beads attached to large numbers of oligonucleotides containing barcodes. Often, the beads provides herein are degradable. For example, they may contain disulfide bonds that are susceptible to reducing agents. The methods provided herein include methods of making libraries of barcoded beads as well as methods of combining the beads with a sample, such as by using a microfluidic device.
    Type: Grant
    Filed: August 1, 2018
    Date of Patent: June 18, 2019
    Assignee: 10X GENOMICS, INC.
    Inventors: Christopher Hindson, Michael Schnall-Levin, Andrew Price, Paul Hardenbol, Yuan Li
  • Patent number: 10323282
    Abstract: The invention is directed to methods and compositions for collecting a non-placental biological samples of cells and quantifying and comparing levels of expression of microRNAs to characterize a preeclampsia-related condition. The samples may be collected before or after an intervention or may be collected over a period of time. One of the samples may be a control sample. Patients may then be treated according to their response.
    Type: Grant
    Filed: May 21, 2013
    Date of Patent: June 18, 2019
    Assignee: Edward E. Winger, M.D., Professional Corporation
    Inventors: Edward E. Winger, Jane L. Reed
  • Patent number: 10318704
    Abstract: Disclosed are methods for determining copy number variation (CNV) known or suspected to be associated with a variety of medical conditions, including syndromes related to CNV of subchromosomal regions. In some embodiments, methods are provided for determining CNV of fetuses using maternal samples comprising maternal and fetal cell free DNA. Some embodiments disclosed herein provide methods to improve the sensitivity and/or specificity of sequence data analysis by removing within-sample GC-content bias. In some embodiments, removal of within-sample GC-content bias is based on sequence data corrected for systematic variation common across unaffected training samples. In some embodiments, syndrome related biases in sample data are also removed to increase signal to noise ratio. Also disclosed are systems for evaluation of CNV of sequences of interest.
    Type: Grant
    Filed: May 29, 2015
    Date of Patent: June 11, 2019
    Assignee: Verinata Health, Inc.
    Inventors: Darya I. Chudova, Diana Abdueva
  • Patent number: 10301671
    Abstract: Embodiments of the disclosure encompass methods of amplifying nucleic acid from one or more cells using MALBAC (multiple annealing and looping-based amplification cycles) primers. In particular embodiments, the nucleic acid is amplified as amplicons in a linear manner. Specific embodiments include the removal or effective destruction of nonlinearly produced amplicons.
    Type: Grant
    Filed: May 5, 2015
    Date of Patent: May 28, 2019
    Assignee: Baylor College of Medicine
    Inventors: Chenghang Zong, Michael Gundry, Kuanwei Sheng
  • Patent number: 10287623
    Abstract: The present invention is directed to methods, compositions and systems for capturing and analyzing sequence information contained in targeted regions of a genome. Such targeted regions may include exomes, partial exomes, introns, combinations of exonic and intronic regions, genes, panels of genes, and any other subsets of a whole genome that may be of interest.
    Type: Grant
    Filed: June 6, 2016
    Date of Patent: May 14, 2019
    Assignee: 10X GENOMICS, INC.
    Inventors: Mirna Jarosz, Michael Schnall-Levin, Serge Saxonov, Benjamin Hindson, Xinying Zheng
  • Patent number: 10287632
    Abstract: 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.
    Type: Grant
    Filed: December 13, 2016
    Date of Patent: May 14, 2019
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Lian Chye Winston Koh, Stephen R. Quake, Hei-Mun Christina Fan, Wenying Pan
  • Patent number: 10262102
    Abstract: Genomic references are structured as a reference graph that represents diploid genotypes in organisms. A path through a series of connected nodes and edges represents a genetic sequence. Genetic variation within a diploid organism is represented by multiple paths through the reference graph. The graph may be transformed into a traversal graph in which a path represents a diploid genotype. Genetic analysis using the traversal graph allows an organism's diploid genotype to be elucidated, e.g., by mapping sequence reads to the reference graph and scoring paths in the traversal graph based on the mapping to determine the path through the traversal graph that best fits the sequence reads.
    Type: Grant
    Filed: February 24, 2016
    Date of Patent: April 16, 2019
    Assignee: Seven Bridges Genomics Inc.
    Inventor: Richard Brown
  • Patent number: 10248838
    Abstract: A device and method for imaging fluorescently labeled molecules (e.g., nucleic acids) includes securing a modular attachment device to the mobile phone with a sample containing stretched, fluorescently labeled nucleic acid molecules and illuminating the sample with excitation light to cause the fluorescently labeled nucleic acid molecules to emit fluorescent light. Images of the nucleic acids are captured using a camera of the mobile phone. The images from the mobile phone are transferred to a remote computer for image processing and analysis. The images are processed by the remote computer to generate analysis data of sample, wherein the analysis data includes the length of nucleic acid molecules contained in the sample or the length of molecular sub-region(s). The mobile phone or another computing device receives from the remote computer the analysis data and displays at least some of the analysis data thereon.
    Type: Grant
    Filed: December 2, 2016
    Date of Patent: April 2, 2019
    Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
    Inventors: Aydogan Ozcan, Qingshan Wei, Wei Luo
  • Patent number: 10230390
    Abstract: A method of compressive read mapping. A high-resolution homology table is created for the reference genomic sequence, preferably by mapping the reference to itself. Once the homology table is created, the reads are compressed to eliminate full or partial redundancies across reads in the dataset. Preferably, compression is achieved through self-mapping of the read dataset. Next, a coarse mapping from the compressed read data to the reference is performed. Each read link generated represents a cluster of substrings from one or more reads in the dataset and stores their differences from a locus in the reference. Preferably, read links are further expanded to obtain final mapping results through traversal of the homology table, and final mapping results are reported. As compared to prior techniques, substantial speed-up gains are achieved through the compressive read mapping technique due to efficient utilization of redundancy within read sequences as well as the reference.
    Type: Grant
    Filed: August 27, 2015
    Date of Patent: March 12, 2019
    Inventors: Bonnie Berger Leighton, Deniz Yorukoglu, Jian Peng
  • Patent number: 10216895
    Abstract: Accurate variant calling methods for low frequency variants are provided. Sequence reads of targeted ultra-deep sequencing are received and aligned to a reference sequence. Read depths and variant counts for variants of the same class at each location where the reference allele exists on the reference sequence are determined for each sample-amplicon. Based on the read depths and variant counts, a probability value indicating the confidence level that a specific variant at a specific location is a true positive is calculated using methods such as a statistical model based method and a localized method using a reference sample. The probability value is then compared with a threshold level to determine whether the detected variants are true positives.
    Type: Grant
    Filed: May 12, 2015
    Date of Patent: February 26, 2019
    Assignee: Roche Molecular Systems, Inc.
    Inventor: Wei-Min Liu
  • Patent number: 10192024
    Abstract: An embodiment of a method for generating a flow order that minimizes the accumulation of phasic synchrony error in sequence data is described that comprises the steps of: (a) generating a plurality of sequential orderings of nucleotides species comprising a k-base length, wherein the sequential orderings define a sequence of introduction of nucleotide species into a sequencing by synthesis reaction environment; (b) simulating acquisition of sequence data from one or more reference genomes using the sequential orderings, wherein the sequence data comprises an accumulation of phasic synchrony error; and (c) selecting one or more of the sequential orderings using a read length parameter and an extension rate parameter.
    Type: Grant
    Filed: March 13, 2013
    Date of Patent: January 29, 2019
    Assignee: 454 Life Sciences Corporation
    Inventors: Yi-Ju Chen, Chiu Tai Andrew Wong
  • Patent number: 10147505
    Abstract: The present invention provides method of classifying a subject into a necrotizing meningoencephalitis (NME) disease risk group. The method may include assessing the presence of one or more marker (e.g., SNPs or risk loci) in a sample from the subject. For example, detection of the presence of one or more markers that are associated with an increased risk of NME can indicate that the subject should be classified into a risk group.
    Type: Grant
    Filed: May 15, 2015
    Date of Patent: December 4, 2018
    Assignees: The Translational Genomics Research Institute, University of Georgia Research Foundation, Inc.
    Inventors: Matthew Huentelman, Scott Schatzberg, Renee Barber
  • Patent number: 10102337
    Abstract: Disclosed herein are methods, compositions and kits for quantitating one or more specific nucleic acids within a plurality of nucleic acids. In some embodiments, a sequencing library is constructed from enriched probe extension products specific for the specific nucleic acids and sequenced. In some embodiments, the resulting reads are used for removing duplicate reads. In some embodiments, counting of verified probes is used to quantitate or determine the number of specific nucleic acid molecules in the starting nucleic acid sample.
    Type: Grant
    Filed: August 6, 2015
    Date of Patent: October 16, 2018
    Assignee: NuGEN Technologies, Inc.
    Inventors: Jonathan Scolnick, Benjamin Schroeder, Douglas Amorese, Stephanie C. Huelga
  • Patent number: 10095832
    Abstract: The invention relates to a method for identifying one or more polymorphisms in nucleic acid samples, comprising: (a) performing a reproducible complexity reduction on a plurality of nucleic acid samples to provide a plurality of libraries of the nucleic acid samples comprising amplified fragments, wherein the reproducible complexity reduction comprises amplifying fragments of the nucleic acid samples using one or more primers to obtain the amplified fragments, and wherein the amplified fragments in each library comprise a unique identifier sequence to indicate origin of each library obtained by the reproducible complexity reduction; (b) combining the plurality of libraries to obtain a combined library and sequencing at least a portion of the combined library to obtain sequences; (c) aligning the sequences to obtain an alignment; and (d) identifying one or more polymorphisms in the plurality of nucleic acid samples.
    Type: Grant
    Filed: January 5, 2018
    Date of Patent: October 9, 2018
    Assignee: Keygene N.V.
    Inventors: Michael Josephus Theresia Van Eijk, Henricus Johannes Adam Van Der Poel
  • Patent number: 10081839
    Abstract: Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.
    Type: Grant
    Filed: January 23, 2017
    Date of Patent: September 25, 2018
    Assignee: Natera, Inc
    Inventors: Matthew Rabinowitz, Milena Banjevic, Zachary Demko, David Johnson, Dusan Kijacic, Dimitri Petrov, Joshua Sweetkind-Singer, Jing Xu
  • Patent number: 10083273
    Abstract: Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.
    Type: Grant
    Filed: July 23, 2013
    Date of Patent: September 25, 2018
    Assignee: Natera, Inc.
    Inventors: Matthew Rabinowitz, Milena Banjevic, Zachary Demko, David Johnson, Dusan Kijacic, Dimitri Petrov, Joshua Sweetkind-Singer, Jing Xu
  • Patent number: 10072077
    Abstract: The present invention relates to an anti-NMDA antibody or fragment or derivative thereof which is effective in inhibiting the deleterious effects of tissue-type plasminogen activator (t-PA) mediated by N-methyl-D-aspartate (NMDA) receptors and to medical uses, in particular for the treatment of neurological or neurodegenerative disorders, e.g. multiple sclerosis.
    Type: Grant
    Filed: May 21, 2014
    Date of Patent: September 11, 2018
    Assignees: PAION DEUTSCHLAND, INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE), UNIVERSITE DE CAEN NORMANDIE
    Inventors: Fabian Docagne, Richard Macrez, Denis Vivien, Karl-Uwe Petersen
  • Patent number: 10073101
    Abstract: A method for the prevention or treatment of scoliosis in a human subject comprising: (a)(i) measuring osteopontin (OPN) protein expression in a biological fluid sample from the subject over time; or (ii) measuring osteopontin (OPN) protein expression in a biological fluid sample from the subject and comparing the OPN protein expression to an OPN protein expression in a control biological fluid sample; (b) identifying the subject as being at risk of developing scoliosis when OPN protein expression increases in the subject sample over time; or when OPN protein expression is higher in the subject sample than that in the control sample; and (c) reducing OPN protein levels in the subject identified as being at risk of developing a scoliosis, thereby aiding in the prevention or treatment of scoliosis.
    Type: Grant
    Filed: July 23, 2015
    Date of Patent: September 11, 2018
    Assignee: CHU SAINTE-JUSTINE
    Inventor: Alain Moreau
  • Patent number: 10059995
    Abstract: The present invention provides a method for determining P1/P2 blood type, including steps of providing a biological sample of a subject, detecting a genotype for single nucleotide polymorphism rs2143918 or rs5751348 in A4GALT gene of the biological sample and determining a phenotype of the subject based on the genotype. Further, the present invention also provides a kit for determining P1/P2 blood type, including a primer pair for detecting a genotype for single nucleotide polymorphisms rs2143918 or rs5751348 in A4GALT gene of a nucleic acid sample of a subject.
    Type: Grant
    Filed: December 14, 2017
    Date of Patent: August 28, 2018
    Assignee: National Taiwan University
    Inventors: Lung-Chih Yu, Marie Lin
  • Patent number: 9994911
    Abstract: Provided herein is technology relating to detecting neoplasia and particularly, but not exclusively, to methods, compositions, and related uses for detecting premalignant and malignant neoplasms such as pancreatic and colorectal cancer. Accordingly, provided herein is technology for pancreatic cancer screening markers and other gastrointestinal cancer screening markers that provide a high signal to-noise ratio and a low background level when detected from samples taken from a subject (e.g., stool sample). As described herein, the technology provides a number of methylated DNA markers and subsets thereof (e.g., sets of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more markers) with high discrimination for G1 neoplasms overall and/or at individual tumor sites.
    Type: Grant
    Filed: March 12, 2014
    Date of Patent: June 12, 2018
    Assignees: MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH, EXACT SCIENCES DEVELOPMENT COMPANY, LLC
    Inventors: David A. Ahlquist, John B. Kisiel, William R. Taylor, Tracy C. Yab, Douglas W. Mahoney, Graham P. Lidgard, Hatim T. Allawi
  • Patent number: 9988678
    Abstract: A semiconductor structure is provided that can be used for DNA sequencing detection. The semiconductor structure includes a doped epitaxial source semiconductor material structure located on a first portion of a semiconductor substrate and a doped epitaxial drain semiconductor material structure located on a second portion of the semiconductor substrate. A gate dielectric portion is located on a third portion of the semiconductor substrate and positioned between the doped epitaxial source semiconductor material structure and the doped epitaxial drain semiconductor material structure. A non-stick nucleotide, DNA and DNA polymerase material structure is located atop the doped epitaxial source semiconductor material structure and atop the doped epitaxial drain semiconductor material structure, wherein a cavity is present in the non-stick nucleotide, DNA and DNA polymerase material structure that exposes a topmost surface of the gate dielectric portion.
    Type: Grant
    Filed: October 26, 2015
    Date of Patent: June 5, 2018
    Assignee: International Business Machines Corporation
    Inventors: Sanghoon Lee, Effendi Leobandung, Renee T. Mo
  • Patent number: 9982310
    Abstract: Provided herein is technology relating to detecting neoplasia and particularly, but not exclusively, to methods, compositions, and related uses for detecting premalignant and malignant neoplasms such as pancreatic and colorectal cancer.
    Type: Grant
    Filed: August 22, 2016
    Date of Patent: May 29, 2018
    Assignee: Mayo Foundation for Medical Education and Research
    Inventors: David A. Ahlquist, John B. Kisiel, William R. Taylor, Tracy C. Yab, Douglas W. Mahoney
  • Patent number: 9965585
    Abstract: Systems, apparatus, and methods are provided for determining genetic or molecular aberrations in a biological sample. Biological samples including cell-free DNA fragments are analyzed to identify imbalances in chromosomal regions, e.g., due to deletions and/or amplifications in a tumor. Multiple loci are used for each chromosomal region. Such imbalances can be used to diagnose (screen) a patient for cancer, as well as prognosticate a patient with cancer, or to detect the presence or to monitor the progress of a premalignant condition in a patient. Severity of an imbalance and the number of regions exhibiting an imbalance can be used. A systematic analysis of non-overlapping genomic segments can provide a general screening tool. A patient can be tested over time to track severity of each of one or more chromosomal regions and a number of chromosomal regions to enable screening and prognosticating, as well as monitoring of progress (e.g. after treatment).
    Type: Grant
    Filed: April 17, 2014
    Date of Patent: May 8, 2018
    Assignee: The Chinese University of Hong Kong
    Inventors: Yuk-Ming Dennis Lo, Kwan Chee Chan, Rossa Wai Kwun Chiu, Peiyong Jiang
  • Patent number: 9944993
    Abstract: The present invention provides a method and a reagent for enrichment of circulating tumor DNA, the method comprising the steps of mixing a water phase and an oil phase and shaking the mixture to prepare an emulsion PCR reaction system, and performing emulsion PCR amplification, wherein the water phase comprises peripheral blood plasma DNA as template DNA, a forward primer and a reverse primer, dNTPs, a PCR buffer and a DNA polymerase, the peripheral blood plasma DNA having adapter sequences connected to both ends thereof, and the forward primer and the reverse primer being complementary to the adapter sequences at the two ends respectively; separating the water phase from the oil phase following the emulsion PCR amplification to obtain a PCR amplification product in the water phase; and capturing circulating tumor DNA in the PCR amplification product in the water phase by using a probe sequence that specifically binds to the circulating tumor DNA.
    Type: Grant
    Filed: January 6, 2015
    Date of Patent: April 17, 2018
    Assignee: Haplox Biotechnology (Shenzhen) Co., Ltd.
    Inventors: Mingyan Xu, Xiaoni Zhang
  • Patent number: 9944977
    Abstract: The invention generally relates to methods for distinguishing a rare genetic variation in a nucleic acid sequence.
    Type: Grant
    Filed: December 12, 2014
    Date of Patent: April 17, 2018
    Assignee: Raindance Technologies, Inc.
    Inventors: Darren R. Link, Michael Samuels
  • Patent number: 9910955
    Abstract: The disclosure provides methods to assemble genomes of eukaryotic or prokaryotic organisms. The disclosure further provides methods for haplotype phasing and meta-genomics assemblies.
    Type: Grant
    Filed: May 27, 2016
    Date of Patent: March 6, 2018
    Assignee: The Regents of the University of California
    Inventors: Richard E. Green, Jr., Liana F. Lareau
  • Patent number: 9869657
    Abstract: A sol-gel deposition technique that forms ion sensitive layers is compatible with CMOS fabrication methods and is applied to build sensors of concentrations of solutions of selected target ions. The ion sensitive sensor may be formed on an exposed portion of a signal trace of a printed circuit board. Additionally, the ion sensitive layer may be formed within an ion sensitive field effect transistor.
    Type: Grant
    Filed: April 21, 2014
    Date of Patent: January 16, 2018
    Assignee: Elemental Sensor LLC
    Inventors: Oliver King-Smith, Eric Kerstan Hoobler
  • Patent number: 9863930
    Abstract: Various molecular barcoded bi-stable switches are provided that can be used to detect various analytes. An electrical current is provided through a pore to electrophoretically draw at least a portion of one or more molecular barcoded bi-stable switches from one volume through one or more pores to another volume. Each molecular barcoded bi-stable switch includes a status identifier that provides an indication when a binding material is bound to the analyte. Each molecular barcoded bi-stable switch also includes a barcode that can be read as it passes through the pore to ascertain the identity of the particular molecular barcoded bi-stable switch.
    Type: Grant
    Filed: February 25, 2016
    Date of Patent: January 9, 2018
    Assignee: APTASCAN, INC.
    Inventor: Timothy Lee Sauder
  • Patent number: 9845552
    Abstract: Disclosed are methods and tools for rapidly aligning reads to a reference sequence. These methods and tools employ Bloom filters or similar set membership testers to perform the alignment. The reads may be short sequences of nucleic acids or other biological molecules and the reference sequences may be sequences of genomes, chromosomes, etc. The Bloom filters include a collection of hash functions, a bit array, and associated logic for applying reads to the filter. Each filter, and there may be multiple of these used in a particular application, is used to determine whether an applied read is present in a reference sequence. Each Bloom filter is associated with a single reference sequence such as the sequence of a particular chromosome. In one example, chromosomal abundance is determined by aligning reads from a sequencer to multiple chromosomes, each having an associated Bloom filter or other set membership tester.
    Type: Grant
    Filed: October 18, 2012
    Date of Patent: December 19, 2017
    Assignee: Verinata Health, Inc.
    Inventors: Erich D. Blume, John P. Burke, Hui Huang
  • Patent number: 9797014
    Abstract: The invention relates to a method of identifying VDJ recombination products which comprises the use of sequence specific enrichment and specific restriction endonuclease enzymes or other DNA-shearing approaches to provide high resolution and high throughput interrogation of antigen receptor repertoires.
    Type: Grant
    Filed: March 1, 2013
    Date of Patent: October 24, 2017
    Assignee: The Babraham Institute
    Inventors: Andrew Wood, Daniel Bolland, Louise Matheson, Anne Corcoran
  • Patent number: 9752179
    Abstract: The present invention provides a method of identifying mRNA transcripts in the transcriptome of a cell comprising i) delivering into the cell a donor expression vector comprising nucleotides in a sequence encoding a trans-splicing barcode cassette, ii) exposing the cell to conditions such that the cell produces multiple copies of the trans-splicing barcode cassette encoded by the donor expression vector, which multiple copies of the trans-splicing barcode cassette each splice the barcode polynucleotide onto a mRNA transcript of the cell, thereby forming multiple mRNA transcripts of the cell, each spliced to the barcode polynucleotide; and iii) identifying the multiple mRNA transcripts that are spliced to the barcode polynucleotides, thereby identifying mRNA transcripts in the transcriptome of the cell.
    Type: Grant
    Filed: March 13, 2014
    Date of Patent: September 5, 2017
    Assignee: COLD SPRING HARBOR LABORATORY
    Inventors: Anthony M. Zador, Ian D. Peikon, Petr Znamenskiy
  • Patent number: 9708654
    Abstract: The present disclosure generally relates to sequencing two or more genes expressed in a single cell in a high-throughput manner. More particularly, the present disclosure relates to a method for high-throughput sequencing of pairs of transcripts co expressed in single cells (e.g., antibody VH and VL coding sequence) to determine pairs of polypeptide chains that comprise immune receptors.
    Type: Grant
    Filed: June 17, 2013
    Date of Patent: July 18, 2017
    Assignee: Board of Regents, The University of Texas System
    Inventors: Scott Hunicke-Smith, Brandon Dekosky, Andy Ellington, George Georgiou
  • Patent number: 9507833
    Abstract: In accordance with the teachings described herein, systems and methods are provided for estimating quantiles for data stored in a distributed system. In one embodiment, an instruction is received to estimate a specified quantile for a variate in a set of data stored at a plurality of nodes in the distributed system. A plurality of data bins for the variate are defined that are each associated with a different range of data values in the set of data. Lower and upper quantile bounds for each of the plurality of data bins are determined based on the total number of data values that fall within each of the plurality of data bins. The specified quantile is estimated based on an identified one of the plurality of data bins that includes the specified quantile based on the lower and upper quantile bounds.
    Type: Grant
    Filed: April 29, 2016
    Date of Patent: November 29, 2016
    Assignee: SAS Institute Inc.
    Inventors: Georges H. Guirguis, Scott Pope, Oliver Schabenberger
  • Patent number: 9506116
    Abstract: Provided herein is technology relating to detecting neoplasia and particularly, but not exclusively, to methods, compositions, and related uses for detecting premalignant and malignant neoplasms such as pancreatic and colorectal cancer.
    Type: Grant
    Filed: March 12, 2014
    Date of Patent: November 29, 2016
    Assignee: MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH
    Inventors: David A. Ahlquist, John B. Kisiel, William R. Taylor, Tracy C. Yab, Douglas W. Mahoney
  • Patent number: 9487828
    Abstract: The technology described herein is directed to methods of determining oligonucleotide sequences, e.g. by enriching target sequences prior to sequencing the sequences.
    Type: Grant
    Filed: March 11, 2013
    Date of Patent: November 8, 2016
    Assignee: The General Hospital Corporation
    Inventors: Anthony John Iafrate, Long Phi Le, Zongli Zheng
  • Patent number: 9487592
    Abstract: An antibody-fragment-immobilizing substrate includes a substrate and at least one set of antibody fragments, wherein the antibody fragments of each set includes at least two types of separate antibody fragments that are capable of recognizing one type of antigen and that are independently immobilized on the substrate in a positional relationship that allows each of the antibody fragments in one set to bind to the same antigen.
    Type: Grant
    Filed: October 23, 2009
    Date of Patent: November 8, 2016
    Assignees: FUJIFILM Corporation, THE UNIVERSITY OF TOKYO
    Inventors: Koichi Minami, Hirohiko Tsuzuki, Hiroshi Ueda, Masaki Ihara
  • Patent number: 9469870
    Abstract: A method of monitoring amplification of a nucleic acid by providing a nucleic acid and an amplification mixture using the kit of isothermal reagents to a pH sensor or pH indicator, amplifying the nucleic acid using isothermal amplification, and detecting a change in pH due to the amplification using the pH sensor or pH indicator. The kit of reagents comprises a magnesium salt, a quaternary ammonium salt, and an alkali base.
    Type: Grant
    Filed: July 16, 2012
    Date of Patent: October 18, 2016
    Assignee: DNAE GROUP HOLDINGS LIMITED
    Inventors: Maurizio Lamura, Angel Chan-Ju Wang, Alpesh Patel
  • Patent number: 9431387
    Abstract: A device comprising an electrostatic discharge protection structure, an ion sensitive field effect transistor (ISFET) having a floating gate, and a sensing layer located above the floating gate. The device is configured such that the electrical impedance from the sensing layer to the electrostatic discharge protection structure is less than the electrical impedance from the sensing layer to the floating gate. The device can be fabricated in a standard CMOS process.
    Type: Grant
    Filed: November 10, 2015
    Date of Patent: August 30, 2016
    Assignee: DNAE GROUP HOLDINGS LIMITED
    Inventors: David Garner, Hua Bai
  • Patent number: 9404880
    Abstract: The sensor includes a first graphene film that is provided on the insulating layer so as to be located in a flow path of a liquid containing the detection target substance, the first graphene film having a first edge that is parallel with a first direction that is along the flow path and a first edge that is parallel with a second direction that is different from the first direction, and the first graphene film having the shape of a band that extends in the second direction. The sensor includes a first electrode that is electrically connected to the first edge of the first graphene film that is parallel with the first direction. The sensor includes a second electrode that is electrically connected to a second edge of the first graphene film that is opposed to the first edge that is parallel with the first direction.
    Type: Grant
    Filed: September 8, 2015
    Date of Patent: August 2, 2016
    Assignee: KABUSHIKI KAISHA TOSHIBA
    Inventors: Tatsuro Saito, Masayuki Kitamura, Atsuko Sakata, Akihiro Kajita, Atsunobu Isobayashi, Tadashi Sakai
  • Patent number: 9389220
    Abstract: The present disclosure relates generally to drug discovery and development and, more particularly, to in vitro assay systems and methods for selecting lead anti-cancer agents for subsequent testing in human and non-human subjects. The present disclosure allows filtering for candidate anti-cancer agents that are not inactivated by liver enzymes, are able to diffuse through cell layers, are not toxic to bone marrow cells, retain anti-cancer activity in the context of stromal support, and are effective after time-limited exposure mimicking non-hepatic clearance by kidneys and other mechanisms.
    Type: Grant
    Filed: January 30, 2015
    Date of Patent: July 12, 2016
    Assignee: The Cleveland Clinic Foundation
    Inventors: Frederic J. Reu, Sergei Vatolin
  • Patent number: 9365634
    Abstract: Based on our identification of a polypeptide (Angiopep-7) that is efficiently transported to cells such as liver, lung, kidney, spleen, and muscle, the invention provides polypeptides, conjugates including the polypeptides, and methods for treating diseases associated with these cell types. Unlike other aprotinin related polypeptides identified herein (including Angiopep-3, Angiopep-4a Angiopep-4b Angiopep-5, and Angiopep-6) which efficiently cross the blood-brain barrier (BBB), Angiopep-7 is not efficiently transported across the BBB.
    Type: Grant
    Filed: May 29, 2008
    Date of Patent: June 14, 2016
    Assignee: Angiochem Inc.
    Inventors: Richard BĂ©liveau, Michel Demeule, Christian Che, Anthony Regina
  • Patent number: 9267165
    Abstract: The invention provides methods for determining the interactions between phage-displayed proteins and test molecules. The phage-displayed proteins are contacted with a reference moiety in the presence and absence of a test molecule; the behavior of the phage-displayed proteins as a function of concentration of the test molecule permits calculation of the binding affinity of the phage-displayed protein for the test molecule.
    Type: Grant
    Filed: August 23, 2007
    Date of Patent: February 23, 2016
    Assignee: DiscoveRx Corporation
    Inventors: David J. Lockhart, Patrick Parvis Zarrinkar, Daniel Kelly Treiber
  • Patent number: 9249468
    Abstract: Described herein are methods for diagnosing ovarian cancer. In particular, certain microRNAs are useful to the response to chemotherapy of ovarian cancer patients.
    Type: Grant
    Filed: October 15, 2012
    Date of Patent: February 2, 2016
    Assignee: The Ohio State University
    Inventors: Carlo M. Croce, Andrea Vecchione
  • Patent number: 9218450
    Abstract: Accurate and fast mapping of sequencing reads obtained from a targeted sequencing procedure can be provided. Once a target region is selected, alternate regions of the genome that are sufficiently similar to the target region can be identified. If a sequencing read is more similar to the target region than to an alternate region, then the read can be determined as aligning to the target region. The reads aligning to the target region can then be analyzed to determine whether a mutation exists in the target region. Accordingly, a sequencing read can be compared to the target region and the corresponding alternate regions, and not to the entire genome, thereby providing computational efficiency.
    Type: Grant
    Filed: November 29, 2012
    Date of Patent: December 22, 2015
    Assignee: Roche Molecular Systems, Inc.
    Inventors: Xiaoying Chen, Yan Li, Wei-Min Liu, Xiaoju (Max) Ma, Sim-Jasmine Truong
  • Patent number: 9163094
    Abstract: The invention, in some aspects relates to synthetic, light-activated fusion proteins and their encoding polynucleotide molecules. In some aspects the invention additionally includes expression of the light-activated fusion proteins in cells and their use in methods such as therapeutic methods and candidate compound screening methods.
    Type: Grant
    Filed: September 27, 2012
    Date of Patent: October 20, 2015
    Assignee: Massachusetts Institute of Technology
    Inventors: Daniel Schmidt, Edward Boyden
  • Patent number: 9163329
    Abstract: A method of sample analysis is provided. In certain embodiments, the method involves: a) obtaining a fragmented RNA sample comprising fragments of long RNA molecules and short RNA molecules; b) ligating an adaptor to an end of the RNA of the fragmented RNA sample to produce an adaptor-ligated sample; c) hybridizing said adaptor-ligated sample to an array of nucleic acid probes; and d) reading said array to obtain an estimate of the abundance of a long RNA in the RNA sample and an estimate of the abundance a small RNA in the RNA sample.
    Type: Grant
    Filed: January 19, 2012
    Date of Patent: October 20, 2015
    Assignee: Agilent Technologies, Inc.
    Inventors: Emily Marine Leproust, Gusti Zeiner, Petula N. D'andrade
  • Patent number: 9074204
    Abstract: Described herein are methods useful for incorporating one or more adaptors and/or nucleotide tag(s) and/or barcode nucleotide sequence(s) one, or typically more, target nucleotide sequences. In particular embodiments, nucleic acid fragments having adaptors, e.g., suitable for use in high-throughput DNA sequencing are generated. In other embodiments, information about a reaction mixture is encoded into a reaction product. Also described herein are methods and kits useful for amplifying one or more target nucleic acids in preparation for applications such as bidirectional nucleic acid sequencing. In particular embodiments, methods of the invention entail additionally carrying out bidirectional DNA sequencing. Also described herein are methods for encoding and detecting and/or quantifying alleles by primer extension.
    Type: Grant
    Filed: May 21, 2012
    Date of Patent: July 7, 2015
    Assignee: Fluidigm Corporation
    Inventors: Megan Anderson, Peilin Chen, Brian Fowler, Robert C. Jones, Fiona Kaper, Ronald Lebofsky, Andrew May
  • Publication number: 20150148238
    Abstract: The present invention relates to droplet-based surface modification and washing. According to one embodiment, a method of splitting a droplet is provided, the method including providing a droplet microactuator including a droplet including one or more beads and immobilizing at least one of the one or more beads. The method further includes conducting one or more droplet operations to divide the droplet to yield a set of droplets including a droplet including the one or more immobilized beads and a droplet substantially lacking the one or more immobilized beads.
    Type: Application
    Filed: January 30, 2015
    Publication date: May 28, 2015
    Applicants: ADVANCED LIQUID LOGIC, INC., Duke University
    Inventors: Vamsee Pamula, Vijay Srinivasan, Michael G. Pollack, Richard B. Fair