Abstract: The present disclosure provides a method for monitoring residual disease in a subject. Generally, the method comprises determining a frequency of cancer mutations from a first sample obtained from a tumor biopsy from the subject; determining a frequency of the cancer mutations discovered in the first sample from a second sample comprising cell-free deoxyribonucleic acid (cfDNA) molecules that is obtained from the subject after the subject has undergone a course of treatment for cancer; and determining a presence or absence of cancer in the subject based on an analysis of the frequency of the cancer mutations from sequence data from the second sample, wherein adapters are ligated to at least 20% of the cfDNA molecules using more than a 10× molar excess of adapters relative to the cfDNA molecules in the population of cfDNA molecules.

Abstract: Methods and compositions for analyzing a library comprising a plurality of amplicons comprising identifier sequences are provided, for example, a library of amplicons in a cell or tissue sample attached to a solid support. For example, amplicons are sequenced using a polymerase to incorporate a plurality of cognate nucleotides into the sequencing primer or an extension product thereof to generate a plurality of extension products.

Abstract: Methods of uniquely labeling or barcoding molecules within a cell, a plurality of cells, and/or a tissue are provided. Kits for uniquely labeling or barcoding molecules within a cell, a plurality of cells, and/or a tissue are also provided. The molecules to be labeled may include, but are not limited to, RNAs, cDNAs, DNAs, proteins, peptides, and/or antigens.

Abstract: The disclosure provides methods for creating long oligonucleotide reagents that include barcodes and other element for sequencing library preparation, where the oligonucleotides are created by multiple tiers of ligation of shorter oligos. The disclosed methods work to extend short oligos that are attached to particles, thereby allowing one to create particles that carry large number of long sample preparation oligonucleotides without being required to synthesize those full-length molecules with a polymerase.

Abstract: The invention provides methods of performing multi-parameter analysis of single cells. Specifically, the present invention is based, in part, on leveraging a separation of reaction volume scales to conduct high-throughput single cell multi-parameter measurements and library preparation on the same single cell using double emulsion micro-droplets and sorting using flow cytometry.

Abstract: Described herein are probiotics, more particularly [to] the probiotic yeast Saccharomyces boulardii. Even more particularly described herein are enhanced probiotic potency S. boulardii. Also described here are mutant alleles useful to develop yeast strains with enhanced production of acetic acid. In addition, described here is the use of such yeast strains for the production of dietary supplements or pharmaceutical compositions to improve gastrointestinal comfort.

Abstract: Single use cartridges for testing biological samples are provided that include multiple processing channels. A single use cartridge includes an aliquot staging well, a first amplification well, a second amplification well, an actuation port, and a fluid channel control valve assembly. The fluid channel control valve assembly is reconfigurable between a first fluid channel configuration and a second fluid channel configuration.

Abstract: The present disclosure relates in some aspects to methods and compositions for analysis of a target nucleic acid, such as in situ detection of a region of interest in a polynucleotide in a tissue sample. In some embodiments, provided herein are templated ligation probes (e.g., RNA-templated ligation probes) and selector probes for generation of a circularized ligated probe comprising an insertion sequence of a selector probe, wherein the circularized ligated probe is amplified in a rolling circle amplification reaction to generate a product that is detected in the sample.

Abstract: The present disclosure provides a method for monitoring residual disease in a subject. Generally, the method comprises determining a frequency of cancer mutations from a first sample obtained from a tumor biopsy from the subject; determining a frequency of the cancer mutations discovered in the first sample from a second sample comprising cell-free deoxyribonucleic acid (cfDNA) molecules that is obtained from the subject after the subject has undergone a course of treatment for cancer; and determining a presence or absence of cancer in the subject based on an analysis of the frequency of the cancer mutations from sequence data from the second sample.

Abstract: The present disclosure provides methods and systems for processing nucleic acid molecules from one or more cells. A cell may be comprised in a cell bead. Processing may comprise uniquely identifying nucleic acid molecules. Nucleic acid molecules may be identified by barcoding. Barcoding may be combinatorial barcoding. Combinatorial barcoding may allow for generation of a large number of barcodes, thereby uniquely identifying nucleic acids from a large number of single cells. Combinatorial barcoding may be performed in successive operations. Successive operations may be performed in partitions.

Abstract: Provided herein relates to DNA polymerase variants and kits including the same, where the DNA polymerase variant has an improved function and activity of performing template-independent nucleic acids synthesis using canonical nucleotides and non-canonical nucleotide analogues in a thermotolerant manner.

Abstract: Compositions and methods are provided for detection of dynamic loci in a genome, where such loci may comprise structural variations as a result of DNA recombination; DNA duplication, insertions, deletions, transpositions, and epigenetic changes. The methods may utilize microfluidic platforms and functionalized polymer matrices to allow determination of mechanisms of cell-type-specific, programmed genomic heterogeneity. The method and compositions allow determination of mechanisms of cell-type-specific, programmed genomic heterogeneity.

Abstract: Provided is a method of fabricating a hybrid element, the method including forming a plurality of first elements on a first substrate, separating a plurality of second elements grown on a second substrate from the second substrate, a material of the second substrate being different from a material of the first substrate, and transferring the plurality of second elements, separated from the second substrate, onto the first substrate, wherein, in the transferring, the plurality of second elements are spaced apart from each other by a fluidic self-assembly method, and wherein each of the plurality of second elements includes a shuttle layer grown on the second substrate, an element layer grown on the shuttle layer, and an electrode layer on the element layer.

Abstract: A method for low frequency somatic cell mutation identification and quantification, relating specifically to a method for transposon copy number and genome location identification. Specific sites of different transposon families are used, transposon insertion sequences are specifically enriched via library construction, high-throughput sequencing and bioinformatics analysis are used, and genome locations, copy numbers and types of transposons within samples are accurately identified. The method economically and accurately identifies copy numbers and genome locations of transposons.

Abstract: Provided herein are methods of normalizing nucleic acid libraries. The method uses nucleic acid probes with nucleic acid sequences that are complementary to one or more of these adaptor sequences are added to the nucleic acids libraries. The probes can hybridize to the adaptor sequences in the single stranded nucleic acid molecules derived from the libraries to form hybridization complexes. The probes are conjugated to a first binding member, which can interact with a second binding member that is conjugated to solid supports. The solid supports can then be collected and the single stranded nucleic acid molecules can be recovered in a volume of elution buffer to reach a desired concentration. As compared to standard methods, the methods are more efficient and cost-effective.

Abstract: Compositions, kits and methods are described that comprise one or more constructs, each construct comprising a ligand attached or conjugated to a polymer construct, e.g., an oligonucleotide sequence, by a linker, each ligand binding specifically to a single target located in or on the surface of a cell. The polymer construct comprises a) an Amplification Handle; b) a Barcode that specifically identifies a single ligand; c) an optional Unique Molecular Identifier that is positioned adjacent to the Barcode on its 5? or 3? end; and d) an Anchor for hybridizing to a complementary sequence, e.g., for generation of a double-stranded oligonucleotide. These compositions are used in methods, including high throughput methods, for detecting one or more targets or epitopes in a biological sample. These compositions are also used in a high throughput method for characterizing a cell by simultaneous detection of one or more epitopes located in or on the cell and its transcriptome.

Abstract: Disclosed herein is a specific B-family DNA polymerase variants that exhibit an improved incorporation of nucleotide analogues for synthesizing polynucleotides and sequencing the associated nucleic acid template. More particularly, the DNA sequencing-by-synthesis method can be efficiently performed by said B-family DNA polymerase variants with a normal nucleic acid template and reversible dye-terminator nucleotides to precisely determine the sequence of associated nucleic acid template.

Abstract: The present disclosure provides methods and systems for producing full-length sequencing information of transcriptomes from single cells or from the bulk. Random ligation and circularization of barcoded or non-barcoded complementary deoxyribonucleic molecules can be used to provide a circular template for amplification and subsequent sequencing.

Abstract: A method for prioritizing sequencing of nucleic acid molecules from two or more sources, comprising: (i) ligating one or more ends of each of a plurality of nucleic acid molecules to an adapter, wherein the adaptor is unique to each source and comprises a unique identifier nucleic acid sequence; (ii) pooling the nucleic acid molecules from each of the two or more sources; (iii) sequencing a plurality of nucleotides of an identifier nucleic acid sequence of an adapter; (iv) determining in real-time from which of the two or more sources the nucleic acid molecule being sequenced came; (v) determining, from a prioritization rule set and based on the determined source, a sequencing priority for the nucleic acid molecule; and (vi) allowing the sequencing process to proceed, or modifying the sequencing process, based on the determined sequencing priority.

Abstract: An anti-SIRP? antibody that can be used as a tumor agent and an anti-tumor agent comprising the antibody as an active ingredient. An antibody that binds specifically to human SIRP? to inhibit binding of human SIRP? to CD47.

Abstract: Glycerol-free enzyme formulations are described. In some embodiments, a glycerol-free enzyme formulation is stabilized by high salt concentration. The glycerol free enzyme formulation may comprise a reverse transcriptase enzyme.

Abstract: The present invention discloses devices for independently-controllable, multi-chamber cuvettes for rapid, concurrent spectral analyses, embodied applications of same, and methods therein. Devices include: a multi-chamber cuvette having contiguous analysis chambers forming a single continuous inner cavity configured to contain a liquid in an inner-cavity volume, wherein each chamber is configured to serve as a measurement zone for the liquid in the inner cavity when the volume is filled with the liquid by regulation of hydrostatic pressure in the inner cavity in order to prevent fluid flow from a given chamber to another chamber, and wherein each volume in each zone is designated a zone volume; thermal-contact windows positioned in a chamber to enable independent temperature control of a zone volume in a zone; and cuvette optical windows, positioned in each chamber to provide independent optical access to each zone, adapted to enable analysis of each zone volume in each zone.

Abstract: A process for analysing chromosome regions and interactions relating to ALS and Huntington's disease.

Abstract: Described herein are compositions and methods for the production and quantification of barcoded or unique molecular identifier (UMI)-labeled substrates. In one aspect, the substrate is a bead comprising a template oligonucleotide that is elongated by successive extension reactions to provide a bead with an oligonucleotide comprising a plurality of barcodes and conserved anchor regions. Methods are also described for quantifying the amount of template oligonucleotide loaded onto the substrate and the products of the extension reaction after each round and after the final extension.

Abstract: A microfluidic device includes an array unit and a nanostructure connected to the array unit, wherein the array unit comprises array cells with substances for a polymerase chain reaction. The array cells include nucleotides with stop properties according to the Sanger sequencing method and primers for an asymmetric polymerase chain reaction. The nanostructure is configured to determine lengths of nucleotide strands formed by the polymerase chain reaction.

Abstract: The present technology relates to methods for determining whether a patient diagnosed with breast cancer, colorectal cancer, melanoma or lung cancer will benefit from or is predicted to be responsive to treatment with an individual therapeutic agent or a specific combination of therapeutic agents. These methods are based on screening a patient's solid tumors and detecting alterations in target nucleic acid sequences corresponding to a specific set of cancer-related genes. Kits for use in practicing the methods are also provided.

Abstract: The present disclosure relates to a next generation DNA sequencing method and use for accurate and massively parallel quantification of one or more nucleic acid targets, for example in large volumes of unpurified sample material. More particularly, the disclosed embodiments is related to a method and a kit comprising probes for detecting and quantifying genetic targets in complex samples. The disclosed embodiments includes two target-specific nucleic acid probes per genetic target, a barcode loop oligo and a bridge oligo or bridge oligo complex.

Abstract: Provided herein are systems and methods for processing biomolecules (e.g., nucleic acid molecules, proteins) from a sample. A method for processing biomolecules may comprise hybridizing a probe molecule to a target region of a nucleic acid molecule (e.g., a ribonucleic acid (RNA) molecule) and barcoding the probe-nucleic acid molecule complex or derivatives thereof. Such a method can comprise performing a nucleic acid reaction, e.g., extension, denaturation, and amplification. A method for processing a sample may comprise hybridizing probes to (i) target regions of a nucleic acid molecule (e.g., RNA molecule) and (ii) a reporter oligonucleotide of a feature binding group, and barcoding the probe-associated molecules. One or more processes of the methods described herein may be performed within a partition, such as a droplet or well.

Abstract: The invention provides improved methods, compositions, and kits for detecting ploidy of chromosome regions, e.g. for detecting cancer or a chromosomal abnormality in a gestating fetus. The methods can utilize a set of more than 200 SNPs that are found within haploblocks and can include analyzing a series of target chromosomal regions related to cancer or a chromosomal abnormality in a gestating fetus. Finally the method may use knowledge about chromosome crossover locations or a best fit algorithm for the analysis. The compositions may comprise more than 200 primers located within haplotype blocks known to show CNV.

Abstract: A cell analyzing device includes a control circuit. The control circuit acquires data of an observation image. The control circuit specifies a colony of a cultured cell in the observation image. The control circuit calculates a ratio at which the cultured cell occupies a predetermined range included in the observation image as an occupancy rate. The control circuit calculates a size of the colony. The control circuit determines a state of the cultured cell based on the occupancy rate and the size of the colony.

Abstract: Provided herein are compositions and methods for accurate and scalable Primary Template-Directed Amplification (PTA) nucleic acid amplification and sequencing methods, and their applications for research, diagnostics, and treatment.

Abstract: This disclosure relates to methods for increasing capture efficiency of a spatial array using rolling circle amplification of a padlock probe that hybridizes to a capture probe. Also provided are methods for using such spatial arrays to detect a biological analyte in a biological sample.

Abstract: Disclosed herein, inter alia, are methods and systems of image analysis useful for identifying and/or quantifying features in patterns.

Abstract: There is disclosed a method of generating a massively parallel sequencing library comprising the steps of: a) providing a primary WGA DNA library (pWGAlib), including fragments comprising a WGA library universal sequence adapter; b) performing a single PCR cycle on the pWGAlib using a first primer (1PR) comprising from 5? to 3? a first sequencing adapter (1PR5SA) and a first primer 3? section (1PR3S) hybridizing to the reverse complementary of the WGA library universal sequence adapter; c) performing a single PCR cycle on the on the product of step b) using a second primer (2PR) comprising from 5? to 3? a second sequencing adapter (2PR5SA) different from the 1PR5SA, and a second primer 3? section (2PR3S) hybridizing to the WGA library universal sequence adapter reverse complementary; d) amplifying by PCR the product of step c) using a third primer comprising the 1PR5SA and a fourth primer comprising 2PR5SA.

Abstract: Provided are methods and related devices for preparing a cell and tissue culture, including a hanging drop culture. Microwells are specially loaded with cell mixtures using a removable reservoir and forcing cells into the underlying microwells. The removable reservoir is removed and the cells partitioned into the individual microwells and covered by an immiscible layer of fluid. The microwells and immiscible layer is inverted and the cells in the microwells cultured. The microwells may have shape-controlling elements to control the three-dimensional shape of the culture.

Abstract: A method for sequencing a biological molecule, such as a nucleic acid molecule, and a method for detecting and/or correcting sequencing error(s) in the sequencing results are provided. Kits and systems based on the above methods are also provided.

Abstract: A method of determining responsiveness to therapy for rheumatoid arthritis.

Abstract: The technology disclosed processes input data through a neural network and produces an alternative representation of the input data. The input data includes per-cycle image data for each of one or more sequencing cycles of a sequencing run. The per-cycle image data depicts intensity emissions of one or more analytes and their surrounding background captured at a respective sequencing cycle. The technology disclosed processes the alternative representation through an output layer and producing an output and base calls one or more of the analytes at one or more of the sequencing cycles based on the output.

Abstract: Methods of generating a nucleic acid signature for identifying particles associated in a partition are provided. In one aspect, the method comprises: partitioning a sample into a plurality of partitions comprising a particle comprising a solid support surface, the solid support surface having a plurality of oligonucleotide primers conjugated thereon, wherein the oligonucleotide primers comprise a barcode sequence, and wherein the partitions have 0, 1, or more than 1 particles per partition; providing in a partition a substrate comprising a barcode sequence or repeating clonal barcode sequences; and in the partition, associating a first particle conjugated to oligonucleotide primers comprising a first barcode sequence and a second particle conjugated to oligonucleotide primers comprising a second barcode sequence to a barcode sequence from the substrate, thereby generating a nucleic acid signature for the particles in the partition.

Abstract: Provided herein, in some embodiments, are systems, methods, compositions, and kits for detecting and quantifying analytes using a primary analyte binding molecule conjugated to a nucleic acid template.

Abstract: The present invention relates to the analysis of complex single cell sequencing libraries. Disclosed are methods for enrichment of library members based on the presence of cell-of origin barcodes to identify and concentrate DNA that is relevant to interesting cells or components that would be expensive or difficult to study otherwise. Also, disclosed are methods of capturing cDNA library molecules by use of CRISPR systems, hybridization or PCR. The present invention allows for identifying the properties of rare cells in single cell RNA-seq data and accurately profile them through clustering approaches. Further information on transcript abundances from subpopulations of single cells can be analyzed at a lower sequencing effort. The methods also allow for linking TCR alpha and beta chains at the single cell level.

Abstract: According to some embodiments of the present disclosure, a device is disclosed. In embodiments, the device stores a computer program comprised of a set of encoded executable instructions; a genomic differentiation object and genomic regulation instructions (GRI) that were used to encode the set of encoded executable instructions. The device further includes a processing system comprising a VDAX and a set of processing cores. The VDAX is configured to: receive encoded instructions to be executed from the set of encoded executable instructions and decode the encoded instructions into decoded executable instruction based on a modified genomic differentiation object and sequences extracted from metadata associated with the encoded instructions. In these embodiments, the modified genomic differentiation object is modified from the genomic differentiation object using the GRI.

Abstract: Provided herein are methods and systems for establishing the presence of a sequence element in nucleic acid molecules. The sequence element may comprise a fused gene, a reporter gene, or another useful sequence for cell and tissue engineering, such as those used for labeling cells, identifying successfully transfected or transduced cells, etc. A method provided herein may additionally allow for barcoding of nucleic acid molecules and analysis of libraries of barcoded nucleic acid molecules.

Abstract: Provided herein are compositions and methods for accurate and scalable Primary Template-Directed Amplification (PTA) nucleic acid amplification and sequencing methods, and their applications for research, diagnostics, and treatment.

Abstract: Provided herein include methods and compositions for analyzing nucleic acid in individual cells. In some embodiments, the methods herein include generating, within individual cells, fragmented cellular genomic DNA and cDNA copies of cellular RNA molecules, barcoding the fragmented genomic DNA and the cDNA within each cell such that the genomic DNA and the cDNA from the same cell receive the same unique barcode sequence, isolating the barcoded genomic DNA and cDNA, and characterizing one or more features of the individual cells based, at least in part, on sequencing of the isolated barcoded genomic DNA and the cDNA.

Abstract: The invention generally relates to performing sandwich assays in droplets. In certain embodiments, the invention provides methods for detecting a target analyte that involve forming a compartmentalized portion of fluid including a portion of a sample suspected of containing a target analyte and a sample identifier, a first binding agent having a target identifier, and a second binding agent specific to the target analyte under conditions that produce a complex of the first and second binding agents with the target analyte, separating the complexes, and detecting the complexes, thereby detecting the target analyte.

Abstract: Air-matrix digital microfluidics (DMF) apparatuses and methods of using them to prevent or limit evaporation and surface fouling of the DMF apparatus. In particular, described herein are air-matrix DMF apparatuses and methods of using them including thermally controllable regions with a wax material that may be used to selectively encapsulate a reaction droplet in the air gap of the apparatus; additional aqueous droplets may be combined with the encapsulated droplet even after separating from the wax, despite residual wax coating, by merging with an aqueous droplet having a coating of a secondary material (e.g., an oil or other hydrophobic material) that may remove the wax from the droplet and/or allow combining of the droplets.

Abstract: Provided herein are methods of enriching mutated cell free nucleic acids for detection and diagnosis of cancer. Also provided are methods using a CRISPR-Cas system to target and deplete unwanted more abundant cell free nucleic acid sequences thereby enriching for less abundant sequences.

Abstract: Some embodiments described herein relate to a substrate with a surface comprising a silane or a silane derivative covalently attached to optionally substituted cycloalkene or optionally substituted heterocycloalkene for direct conjugation with a functionalized molecule of interest, such as a polymer, a hydrogel, an amino acid, a nucleoside, a nucleotide, a peptide, a polynucleotide, or a protein. In some embodiments, the silane or silane derivative contains optionally substituted norbornene or norbornene derivatives. Method for preparing a functionalized surface and the use in DNA sequencing and other diagnostic applications are also disclosed.

Abstract: This invention relates to, in part, compositions of beta-lactamases and methods of using these enzymes in, for example, gastrointestinal tract (GI tract) disorders such as C. difficile infection (CDI).