Abstract: Various methods, systems, computer readable media, and graphical user interfaces (GUIs) are presented and described that enable a subject, doctor, or user to characterize or classify various types of cancer precisely. Additionally, described herein are methods, systems, computer readable media, and GUIs that enable more effective specification of treatment and improved outcomes for patients with identified types of cancer. Some embodiments of the methods, systems, computer readable media, and GUIs described herein comprise obtaining RNA expression data and/or whole exome sequencing (WES) data for a biological sample from a subject; determining a molecular-functional (MF) profile for the subject; identifying an MF profile cluster with which to associate the MF profile for the subject; and clustering the plurality of MF profiles to obtain the MF profile clusters.

Abstract: The disclosure of the preset invention relates to a new method for preventing or treating tumor progression or tumor recurrence comprising administering to a subject in need thereof a therapeutically effective amount of an agent disrupting Musashi-1 (MSI1)/Argonaute 2 (AGO2) interaction. A composition or pharmaceutical composition for preventing or treating tumor progression or tumor recurrence is also provided, which comprises an agent disrupting Musashi-1 (MSI1)/Argonaute 2 (AGO2) interaction.

Abstract: The present invention provides, among other things, methods of quantitating mRNA capping efficiency, particularly for mRNA synthesized in vitro. In some embodiments, the methods comprise chromatographic methods of quantifying capping efficiency and methylation status of the caps.

Abstract: This disclosure provides, among other things, a method for processing a membrane comprising rolling circle amplification (RCA) products. In some embodiments, this method may comprise: (a) obtaining a porous capillary membrane that comprises fluorescently labeled RCA products that are in or on the membrane; (b) depositing a curable polymer onto the membrane; and (c) curing the curable polymer to encapsulate the RCA products in a solid. In some embodiments, the curable polymer may be a silicone and may be transparent in its solid form. A kit for performing the method and a composition made by the method are also provided.

Abstract: 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.

Abstract: The invention relates to the amplification of specific target nucleic acids. The invention provides methods, reagents, and kits for carrying out such amplification via the autoligation chain reaction (ACR).

Abstract: Text can be encoded into DNA sequences. Each word from a document or other text sample can be encoded in a DNA sequence or DNA sequences and the DNA sequences can be stored for later retrieval. The DNA sequences can be stored digitally, or actual DNA molecules containing the sequences can be synthesized and stored. In one example, the encoding technique makes use of a polynomial function to transform words based on the Latin alphabet into k-mer DNA sequences of length k. Because the whole bits required for the DNA sequences are smaller than the actual strings of words, storing documents using DNA sequences may compress the documents relative to storing the same documents using other techniques. In at least one example, the mapping between words and DNA sequences is one-to-one and the collision ratio for the encoding is low.

Abstract: An amphoteric dissociation ion exchange separation medium, the surface of which is an amphoteric dissociation covalently-modified layer. When an environmental pH value is lower than the isoelectric point, pIm, of the covalently-modified layer, the type of net charges on the surface of the covalently-modified layer is positive and the separation medium has the properties of an anion exchanger; when the environmental pH value is higher than the pIm, the type of net charges on the covalently-modified layer surface is negative and the separation medium has the properties of a cation exchanger. The separation medium has the properties of an anion exchanger and a cation exchanger at both sides of the pIm, respectively. The pH of an eluent can be adjusted to allow the separation medium surface and the target substance to have the same type of net charges, so that the target substance can be released by electrostatic repulsion.

Abstract: Molecules or salts thereof are provided, having the structure in Formula I, wherein n2 and n4 are the same or different and are independently 1, 2, or 3, and n3 is 1 to 20; X is oxygen, nitrogen, or sulfur; wherein R1, R2, R3, R4, R5, R6, and R7 are as described herein. Methods are also provided for the synthesis of and use of the provided molecules in applications for diagnostic testing.

Abstract: A method and system have been provided to perform high speed nucleic acid melting analysis while still obtaining accurate melting curve sufficient for genotyping. This rapid ability to interrogate DNA should be useful whenever time to result is important, such as in molecular point of care testing. Specifically, microfluidics enables genotyping by melting analysis at rates up to 50° C./s, requiring less than is to acquire an entire melting curve. High speed melting reduces the time for melting analysis, decreases errors, and improves genotype discrimination of small amplicons.

Abstract: The present disclosure provides a HTP microbial genomic engineering platform that is computationally driven and integrates molecular biology, automation, and advanced machine learning protocols. This integrative platform utilizes a suite of HTP molecular tool sets to create HTP genetic design libraries, which are derived from, inter alia, scientific insight and iterative pattern recognition. The HTP genomic engineering platform described herein is microbial strain host agnostic and therefore can be implemented across taxa. Furthermore, the disclosed platform can be implemented to modulate or improve any microbial host parameter of interest.

Abstract: The present disclosure provides methods of determining one or more tissues and/or cell-types contributing to cell-free DNA (“cfDNA”) in a biological sample of a subject. In some embodiments, the present disclosure provides a method of identifying a disease or disorder in a subject as a function of one or more determined more tissues and/or cell-types contributing to cfDNA in a biological sample from the subject.

Abstract: Provided herein is reagent mixture comprising multiplexed amplification reagents and flap assay reagents for detecting, in a single reaction, mutant copies of the KRAS gene that contain any of the 34A, 34C, 34T, 35A, 35C, 35T or 38A point mutations. Methods that employ the reagent mix and kits for performing the same are also provided.

Abstract: The invention is a novel method of making and using a library such as a sequencing library of single stranded circular nucleic acid templates via splint ligation. In particular, disclosed are methods of making circular target nucleic acid molecules and libraries of such molecules for downstream analysis such as nucleic acid sequencing. The method comprises the steps of adding universal sequences to nucleic acid molecules, rendering single-stranded these nucleic acid molecules with universal sequences on their ends by contacting with a probe complementary to at least a portion of the universal sequences, and allowing the hybridized probe to enable circularization and formation of single-stranded circular (sscDNA) molecules.

Abstract: A micro-plate reader for use with a portable electronic device having a camera includes an opto-mechanical attachment configured to attach/detach to the portable electronic device and includes an array of illumination sources. A slot in the opto-mechanical attachment is dimensioned to receive an optically transparent plate containing an array of wells. Optical fibers are located in the opto-mechanical attachment and transmit light from each well to a reduced size header having, wherein the fiber array in the header has a cross-sectional area that is ?10× the cross-sectional area of the wells in the plate. A lens located in the opto-mechanical attachment transmits light from the header fibers to the camera. Software executed on the portable electronic device or other computer is used to process the images to generate qualitative clinical determinations and/or quantitative index values for the separate wells.

Abstract: The present invention relates to the field of pharmacogenomics and in particular to detecting the presence or absence of hypermethylated DNA. The detection of CpG methylation in marker DNA is useful for the diagnosis of cancers and the invention provides improved methods for this purpose. These improved methods allow in particular for a more sensitive detection of methylated marker DNA with high backgrounds of unmethylated marker DNA.

Abstract: High-fidelity, high-throughput nucleic acid sequencing enables healthcare practitioners and patients to gain insight into genetic variants and potential health risks. However, previous methods of nucleic acid sequencing often introduce sequencing errors (for example, mutations that arise during the preparation of a nucleic acid library, during amplification, or sequencing). Provided herein are methods and compositions for sequencing nucleic acids. Further provided are methods of identifying an error in a nucleic acid sequence.

Abstract: The present invention relates to DNA microscopy methods to record the cellular co-localization and/or spatial distributions of arbitrary nucleic acid sequences, or other biomolecules tagged with nucleic sequences. The method involves sequence-components which may identify the targeted sequences-of-interest themselves and/or spatial beacons relative to which their distances are measured.

Abstract: A method for identifying a nucleotide in a template nucleic acid by (a) providing a plurality of primer-template nucleic acid hybrids, wherein the primers have an extendable 3? end; (b) contacting the plurality with: (i) blocked nucleotides to produce a first subset of the primer-template nucleic acid hybrids that include a blocked nucleotide at the 3? end, and (ii) a ternary complex inhibitor to produce a second subset of the primer-template nucleic acid hybrids that include a ternary complex inhibitor; (c) forming ternary complexes that each include a polymerase, a primer-template nucleic acid hybrid of the first subset, and a cognate nucleotide; and (d) detecting the ternary complexes, thereby identifying a nucleotide in the template nucleic acid.

Abstract: The invention provides compositions and methods for the diagnosis, treatment, assessment, and characterization of hyperlipidemia-related diseases and disorders, including atherosclerosis, non-alcoholic fatty liver disease, obesity and diabetes mellitus in a subject in need thereof, based on the expression level of at least one miRNA that is associated with these diseases and disorders.

Abstract: The invention relates to a method for the duplication of nucleic acids by means of a polymerase chain reaction, in the case of which a cycle consisting of the steps of denaturing, annealing and elongation is repeatedly performed. In one embodiment, in at least one passage of the cycle, the quotient of the duration of effect tA and the reaction volume Vr irradiated by the energy source is less than 1 seconds per microliter. In another embodiment, in at least one passage of the cycle, the ratio of the duration of effect (tA) and the duration of the PCR cycle (tc) is less than 20%. In certain embodiments, the yield (g) of nucleic acids at the end of at least one of the passages of the cycle is less than 80% of the nucleic acids present at the start of the passage.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into neural crest, cranial placode or non-neuro ectoderm precursors, and cells generated by such methods. The presently disclosed subject matter also provides for uses of such cells for treating neurodegenerative and pituitary disorders.

Abstract: The present disclosure provides compositions, methods and systems for quantifying target sequences and identifying target sequence variants.

Abstract: Provided herein are methods for isolating nucleic acids from intact cells in a sample of intact cells, contamination dead cells, cell debris, and biofilm using two separation steps, either by centrifugation or filtration, performed in sequentially. Also provided is a method for isolating nucleic acids from intact cells using a first separation step followed by treatment with a nuclease and then a second separating step. Provided herein is a related method for isolating DNA from intact cells using a nuclease that produces DNA cuts on double stranded DNA, followed by a second separating step.

Abstract: Disclosed are methods for sequencing immune cell receptor repertoires from immune cell populations, the methods comprising isolating RNA from immune cells, generating cDNA from the RNA, ligating adapter sequences to the cDNA, and sequencing the cDNA. Also provided are kits containing primer mixtures for the sequencing of immune cell receptor repertoires.

Abstract: The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.

Abstract: Embodiments of the present invention relate to sequencing nucleic acids. In particular, embodiments of the methods and compositions provided herein relate to preparing nucleic acid templates and obtaining sequence data therefrom.

Abstract: The present invention provides assays systems and methods for detection of chromosomal abnormalities and status of single loci associated with monogenic or polygenic traits in a sample containing nucleic acids from a maternal and a fetal source.

Abstract: A method of designing a D-polypeptide that binds with an L-target protein can include: identifying a polypeptide target having L-chirality; determining hotspot amino acids of a polypeptide ligand having L-chirality that have binding interactions with the L-target protein; determining transformations of side chains of the hotspot amino acids that retain the binding interactions with the target; generating inversed hotspot amino acids with chirality opposite to the one of the target; identifying a polypeptide having inverse chirality from the target protein, on which a combination of inversed hotspot amino-acid can be grafted without significantly changing their interactions with the target. The designed ligands can be processed and converted to D-ligands that bind with the L-target protein.

Abstract: The invention relates generally to the field of nanopores and the use thereof in various applications, such as analysis of biopolymers and macromolecules, typically by making electrical measurements during translocation through a nanopores. Provided is a system comprising a funnel-shaped proteinaceous nanopore comprising an a-helical pore-forming toxin that is a member from the actinoporin protein family, more in particular Fragaceatoxin C (FraC), a mutant FraC, a FraC paralog, or a FraC homolog.

Abstract: Disclosed are methods utilizing specific amplification of Candida sp. target nucleic acid for detecting the presence or absence of Candida sp. in a sample. Also disclosed are corresponding oligomers, including amplification oligomers, capture probes and detection probes, and combinations thereof, as well as corresponding reaction mixtures and kits.

Abstract: Methods and systems for storing digital data into peptide sequences and retrieving digital data from peptide sequences are disclosed. The method for storing digital data into peptide sequences may include: encoding the digital data into a digital code; translating the digital code into the peptide sequences; and synthesizing the translated peptide sequences. The method for retrieving digital data from peptide sequences may include: sequencing and determining an order of the peptide sequences; converting the peptide sequences with the determined order into a digital code; and decoding the digital data from the digital code. Codes with error-correction capability are developed for encoding digital data into peptide sequences, and a computational method implemented in a software is developed for sequencing the digital data bearing peptides.

Abstract: Technology provided herein relates in part to methods, processes and apparatuses for non-invasive assessment of genetic variations.

Abstract: A system and method for determining the genetic data for one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available, are disclosed. Genetic data for the target individual is acquired and amplified using known methods, and poorly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related subjects. In accordance with one embodiment of the invention, incomplete genetic data is acquired from embryonic cells, fetal cells, or cell-free fetal DNA isolated from the mother's blood, and the incomplete genetic data is reconstructed using the more complete genetic data from a larger sample diploid cells from one or both parents, with or without genetic data from haploid cells from one or both parents, and/or genetic data taken from other related individuals.

Abstract: Methods and devices are provided for sample collection. In one example, a device is provided comprising at least one capillary tube or collection channel directed to a sample vessel, wherein in a one-step removal step of detaching the sample vessel from the collection channel, a vacuum force is created within the sample vessel, due in part of the pulling of the sealed vessel away from the device, wherein this vacuum force draw out residual sample that may still be resident in the collection channel.

Abstract: The present invention relates to the detection of a target nucleic acid sequence by a PTOCE (PTO Cleavage and Extension) assay. The present invention detects a target nucleic acid sequence in which the PTO (Probing and Tagging Oligonucleotide) hybridized with the target nucleic acid sequence is cleaved to release a fragment and the fragment is hybridized with the CTO (Capturing and Templating Oligonucleotide) to form an extended duplex, followed by detecting the presence of the extended duplex. The extended duplex provides signals (generation, increase, extinguishment or decrease of signals) from labels indicating the presence of the extended duplex and has adjustable Tm value, which are well adoptable for detection of the presence of the target nucleic acid sequence.

Abstract: Techniques are described for determining the strain on a cell wall using two models: 1) a short timescale model, describing the relationship between physical properties assumed to be fixed and 2) a long timescale model, describing the dynamic chemical composition of a cell wall. Short term modeling of the physical properties in a cell wall is used to properly understand how physical factors such as osmotic pressure affects the strain on the cell wall, which is in turn used to identify conditions under which a cell wall will cease to function properly or lyse entirely. Although temporally the physical properties which cause cell walls to underperform/lyse can be evaluated under a short time frame, the chemical properties that lead to the physical properties which cause that behavior themselves change over much longer timescales, in a relative sense.

Abstract: Specific, accurate, and cost effective primers for performing digital PCR, compositions and kits containing the primer and methods for using and making the same are useful for detecting nucleic acid mutations. A primer useful as a first forward primer in performing digital PCR to detect a target nucleic acid in a sample, includes: a detection portion located upstream to a target sequence binding portion, and including a second forward primer binding portion having a sequence substantially complementary to a second forward primer, and a probe binding portion downstream to the second forward primer binding portion having a sequence substantially complementary to a probe; the target sequence binding portion includes a mismatch portion having a sequence not complementary to the target nucleic acid, and an amplification determinant portion downstream to the mismatch portion having a sequence complementary to a gene allele or a variant thereof encoded by the target nucleic acid.

Abstract: A method of identifying a polynucleic acid (PNA) is presented, including the steps of providing a PNA; modifying one or more nucleobases of the PNA by addition or removal of a hydrogen bonding partner, thereby altering the base pairing capacity of the one or more nucleobases; base pairing a complementary nucleic acid to the PNA, including base pairing to at least one modified nucleobase; identifying the sequence of the complementary nucleic acid at least at the position that is complementary to at least one modified nucleobase.

Abstract: The present invention provides assay systems and methods for detection of copy number variation at one or more loci and polymorphism detection at one or more loci in a mixed sample from an individual.

Abstract: Contiguity information is important to achieving high-quality de novo assembly of mammalian genomes and the haplotype-resolved resequencing of human genomes. The methods described herein pursue cost-effective, massively parallel capture of contiguity information at different scales.

Abstract: A screening method for the identification of a characteristic of a target nucleic acid in a whole blood sample, including positioning a composition comprising whole blood and at least one preservative agent within a centrifuge, centrifugating the composition to isolate a plasma that includes at least one target nucleic acid for further analysis and analyzing the at least one target nucleic acid to identify a characteristic about the at least one target nucleic acid, and a composition including the plasma, the preservative agent, and any other ingredient, which is produced by the method.

Abstract: Provided herein is technology relating to the amplification-based detection of bisulfite-treated DNAs and particularly, but not exclusively, to methods and compositions for multiplex amplification of low-level sample DNA prior to further characterization of the sample DNA. The technology further provides methods for isolating DNA from blood or blood product samples, e.g., plasma samples.

Abstract: Methods and reagents are provided for the rapid extraction of nucleic acids from a fixed paraffin embedded sample (e.g., a FFPET sample). In some embodiments, the methods comprise incubating one or more sections of said tissue sample in a lysis solution comprising a buffer sufficient to maintain the pH of said solution at a pH ranging from about pH 4 to about pH 9; a chaotropic agent; a chelating agent; and a detergent; where the incubating is at a temperature ranging from about 50° C. to about 100° C.; and recovering the nucleic acid from said lysis solution.

Abstract: The invention discloses a quasi-volumetric sensing system and method. Plural short-range order (SRO) units are configured on the carrier of a quasi-volumetric device, and arranged as an array, i.e. a long-range order (LRO) unit. Protrusions, configured on the SRO units, can modify the wettability of the carrier to control the liquid volume retained thereon so that the precise volume of the liquid sample or droplets are calculated. Based on the applied force on the LRO unit and the gradient of hydrophilicity-hydrophobicity on the surface, the redundant volume of the liquid sample is removed. Macromolecules, e.g. antibodies, complements, receptor proteins, aptamers, oligosaccharides or oligonucleotides, configured on the protrusions are coupled to specific molecules in the liquid sample or droplets so as to determine characteristics of the specific molecules. Therefore, the open chip device of the invention can be used to achieve the quasi-volumetric measurement and the analysis of specific molecules.

Abstract: The present disclosure provides methods, compositions and kits as well as systems for manipulating nucleic acids, including implementing isothermal amplification, such as recombinase-polymerase amplification (RPA), of a nucleic acid template using a pre-seeded solid support. Provided are rapid and efficient methods for generating template nucleic acid molecules comprising specific nucleotide sequence bound to solid support. Such methods can be used, for example, in manipulating nucleic acids in preparation for analysis methods that utilize monoclonal populations of nucleic acids.

Abstract: The present disclosure relates to systems and methods for high efficiency electronic sequencing of nucleic acids and molecular detection.

Abstract: The present disclosure relates to the use of recombinant proteins for inducing epigenetic modifications at specific loci, as well as to methods of using these recombinant proteins for reducing the expression of genes in plants.

Abstract: A microscope stage is movably mounted to a base and is movable relative to the base by two separate drive units on separate rail systems situated at an angle relative to one another. The drive units are mechanically isolated from one another and one of the drive units uses a belt drive.

Abstract: The invention provides a mass spectrometry analysis method and a mass spectrometry system. During implementation of the mass spectrometry analysis method, intensity data of the daughter ions, a first parameter of the daughter ions associated with the first physicochemical property, and a second parameter of the daughter ions associated with the second physicochemical property are all recorded to form a spectrogram data set. In a deconvolution step, the spectrogram data set is deconvoluted to categorize the daughter ions from the same parent ion according to two-dimensional features including the first parameter and the second parameter. In the above manner, the mass spectrometry analysis method and the mass spectrometry system provided by the invention can detect ions that partially overlap spectral peaks of other ions significantly, thereby improving the qualitative and quantitative ability of data analysis for data independent acquisition.