Abstract: Fetal maternal samples taken from pregnant women include both maternal cell-free DNA and fetal cell-free DNA. Described herein are methods for determining a chromosomal abnormality of a test chromosome or a portion thereof in a fetus by analyzing a test maternal sample of a woman carrying said fetus, wherein the test maternal sample comprises fetal cell-free DNA and maternal cell-free DNA. The chromosomal abnormality can be, for example, aneuploidy or the presence of a microdeletion. In some embodiments, the chromosomal abnormality is determined by measuring a dosage of the test chromosome or portion thereof in the test maternal sample, measuring a fetal fraction of cell-free DNA in the test maternal sample, and determining an initial value of likelihood that the test chromosome or the portion thereof in the fetal cell-free DNA is abnormal based on the measured dosage, an expected dosage of the test chromosome or portion thereof, and the measured fetal fraction.

Abstract: Techniques for securely encoding, communicating, and comparing genomic information using probabilistic data structures are provided. In some embodiments, genomic information in a secure computing environment may be encoded and/or anonymized by building a probabilistic data structure that represents sub-strings of the genomic information as members of a set; the probabilistic data structure may then be securely transmitted outside the secure computing environment. In some embodiments, a probabilistic data structure representing sub-strings of sensitive genomic information as members of a set may be received in an unsecure computing environment and may be queried to generate output data indicating whether reference sub-strings are probable members of the set.

Abstract: Methods of analyzing cells, including interactions among different populations of cells. Methods include cell-containing liquid droplets with oligonucleotide-containing liquid droplets, hybridizing oligonucleotides to target nucleic acids from cells, extending the hybridized oligonucleotides on the target nucleic acids into cell identifier sequences on the target nucleic acids, and thereby identifying the type of cells initially present. The methods can be implemented in a high-throughput manner in a microfluidic system.

Abstract: The invention provides methods for determining the MSI status of a patient by liquid biopsy with sample preparation using hybrid capture and non-unique barcodes. In certain aspects, the invention provides a method of detecting microsatellite instability (MSI). The method includes obtaining cell-free DNA (cfDNA) from a sample of blood or plasma from a patient and sequencing portions of the cfDNA to obtain sequences of a plurality of tracts of nucleotide repeats in the cfDNA. A report is provided describing an MSI status in the patient when a distribution of lengths of the plurality of tracts has peaks that deviate significantly from peaks in a reference distribution.

Abstract: A variational autoencoder (VAE) has been developed to learn a continuous numerical, or latent, representation of molecular structure to expand reference libraries for small molecule identification. The VAE has been extended to include a chemical property decoder, trained as a multitask network, to shape the latent representation such that it assembles according to desired chemical properties. The approach is unique in its application to metabolomics and small molecule identification, focused on properties that are obtained from experimental measurements (m/z, CCS) paired with its training paradigm, which involves a cascade of transfer learning iterations. First, molecular representation is learned from a large dataset of structures with m/z labels. Next, in silico property values are used to continue training. Finally, the network is further refined by being trained with the experimental data.

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 method and system for determining a recommendation for drug treatment are described herein. For example, the method includes determining drug scores based upon network-based distances for one or more target drug nodes, modeling one or more outputs based upon input data, wherein the input data comprises at least a portion of the drug scores, selecting an algorithmic output from the one or more modeling outputs based upon at least one performance criteria, determining if the selected algorithmic output of the modeling satisfies a threshold, and if the selected algorithmic output satisfies the threshold, generating the recommendation for drug treatment. The system includes a processing device and computer readable medium including programming instructions that, when executed, cause the processing device to perform the method as described herein.

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: The disclosure provides methods and systems for identifying a subset of compounds in a plurality of compounds. The identifying includes obtaining, for each compound, a vector including a set of elements, where each element includes a measurement of a different feature of an instance of a cell context upon exposure to the compound. The identifying includes repeating the obtaining for a plurality of cell contexts, to obtain a plurality of vectors for each compound across different cell contexts. The identifying includes combining the vectors for each compound to form a combined vector for each compound, thereby forming a plurality of combined vectors representing different compounds. The identifying includes pruning the plurality of compounds to the subset of compounds based on a similarity between respective combined vectors in the plurality of combined vectors corresponding to compounds in the plurality of compounds.

Abstract: Aspects of the present disclosure include systems for use in preparing an epitope tagged biomolecule reagent. A reagent preparatory apparatus for preparing the epitope tagged biomolecule reagent from an activated biomolecule and activated epitope tag is also described. Methods for communicating and receiving an epitope tagged biomolecule reagent request and preparing the subject epitope tagged biomolecule reagents are also provided.

Abstract: The present disclosure relates to probes for analyzing a chemical composition, and related methods of analyzing a chemical composition and of manufacturing probes for analyzing a chemical composition. A benefit of the disclosed probes and methods can include luminescent chemical sensor arrays for rapid, accurate, portable and economical qualitative and quantitative analysis of a broad range of chemical compositions. A benefit of the methods disclosed herein can include the rapid, simple, and accurate analysis of trace chemicals present in chemical compositions.

Abstract: The invention provides compositions and methods for engineering E. coli or other host production bacterial strains to produce fucosylated oligosaccharides, and the use thereof in the prevention or treatment of infection.

Abstract: Provided herein are methods including alternating series of sequencing cycles and dark extension cycles allowing longer read lengths and addressing disadvantages of traditional nucleic acid sequencing protocols.

Abstract: The present invention relates to a bioinformation processing analysis method for the identification and quantification of O-linked glycopeptide using high resolution mass spectrum. Particularly, according to the bioinformation processing analysis method of the present invention, the quantitative changes of O-linked glycopeptide containing non-informed sugar chains included in various samples can be efficiently and accurately analyzed; the prediction or diagnosis of disease including cancer can be made easy by using a high resolution mass spectrometer; or the investigation of O-linked glycopeptide structure of a therapeutic glycoprotein can be efficiently achieved.

Abstract: This invention discloses a signal amplification sandwich structure for amplifying detection signals from proteins, nucleic acids and microbes using a plurality of an electrochemically detectable oligonucleotide tag bound to a multifunctional particle. The invention further discloses a method and device that uses the signal amplification sandwich structure to detect and/or quantify low levels of one or more biological analytes using an off-the-shelf point-of-care electrochemical potentiostat, like a glucose meter for virtually any biological analyte. The invention further discloses a method and device that applies an artificial intelligence (AI) system to recommend actions for assessment and diagnosis of a disease, outbreak or condition with an artificial intelligence learning system to incorporate improvements, additions and modifications to the artificial intelligence systems and its constituents.

Abstract: The present invention relates to methods, systems and kits for the diagnosis, prognosis and the determination of cancer progression of prostate cancer in a subject. The invention also provides clinically useful genomic classifiers for predicting prostate cancer metastasis and identifying tumor aggressiveness. The methods, systems and kits can provide expression-based analysis of biomarkers for purposes of predicting metastatic disease and lethal prostate cancer in a subject. Further disclosed herein, in certain instances, are probe sets for use in predicting prostate cancer metastasis in a subject. Classifiers for predicting prostate cancer metastasis are provided. Methods of treating cancer based on tumor aggressiveness are also provided. The methods and classifiers of the present invention are also useful for predicting early prostate cancer metastasis.

Abstract: Antisense oligonucleotides (ASOs) that disrupt RNA-RNA interactions of influenza virus genome segments that are required for virus packaging are described. The ASOs can be used to inhibit influenza A virus replication in vitro and in vivo. Use of the ASOs for the treatment of a subject with an influenza virus infection is also described.

Abstract: Techniques for identifying and/or classifying genomic information are provided. In some embodiments, genomic information may be identified by computing systems without access to a database of reference genomic information, instead relying on locally stored probabilistic data structures representing reference genomic information. Query genomic data, such as data taken from a read-set, may be divided into sub-strings, and each of the locally-stored probabilistic data structures may be queried by each of the extracted sub-strings, generating probabilistic outputs indicating either that (a) the sub-string is probably included in the set of data represented by the probabilistic data structure or (b) the sub-string is definitely not included in the set of data. Based on the number and/or proportion of sub-strings from a read-set that are indicated as being likely represented by a probabilistic data structure, a likely identity or classification for the genomic information in the read-set may be determined.

Abstract: The present disclosure relates to methods of collecting exosomes and microvesicles (EMV) from urine, isolating corresponding mRNA, and analyzing expression patterns in order to diagnose and treat various urothelial cancers. In particular, various expression patterns are analyzed through a unique diagnostic formula.

Abstract: A system and method for air calibration in a Computed Tomography (CT) imaging system are provided. A first set of data associated with air in a scanning area may be obtained. A second set of data associated with an object in the scanning area may be obtained. The second set of data based on the first set of data may be calibrated, and a set of reference values generated by a neural network model may be used to perform the calibration. A third set of data based on the calibration of the second set of data may be generated. Based on the third set of data, a CT image of the object may be generated.

Abstract: The disclosed invention include nucleic acid oligomers that may be used as amplification oligomers, including primers, as capture probes for sample preparation, and detection probes for detection of 16S rRNA from Atopobium vaginae in samples by using methods of specific nucleic acid amplification and detection.

Abstract: A drug discovery system may include a data platform and a drug discovery module. The data platform may be scalable to include a plurality of data sources. The data sources may include at least a clinical research database providing results of clinical trials. The drug discovery module may include a pharmaco-genomic mapper configured to provide a mapping of drugs to biomarkers based on extraction of information from the data sources, and a genome connect module configured to provide a mapping of biomarkers to diseases based on extraction of information from the data sources. The drug discovery module may include processing circuitry configured to provide a potential drug to disease link based on the mapping of drugs to biomarkers and the mapping of biomarkers to diseases using the biomarkers as a bridge.

Abstract: The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a “design process” comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a “formulation process”, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an “administering” step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition.

Abstract: A method is provided for determining at least one candidate reactant. One embodiment of this method includes the following steps: forming by a computer processor a graph of known reactants and known products, the graph comprising links between the known reactants and their known products, receiving by a computer processor the target compound, determining by a computer processor whether the graph includes the target compound and adding the target compound to the graph if the target compound was not previously included, forming by a computer processor a matrix representing at least a portion of the known reactants, a portion of the known products and the target compound, providing a matrix value of the graph by a computer processor for one or more candidate reactants and determining by a computer processor at least one link in the graph between the target compound and the candidate reactant based on matrix values.

Abstract: Examples of a method to use in an electronic device, an electronic device, and a machine-readable non-transitory storage medium are disclosed herein. An example of the machine-readable non-transitory storage medium includes instructions executable by a processor of an electronic device to generate a molecular signature tag based on molecular signature data representative of a determined molecular structure of an object scanned by a molecular detector of the electronic device and to embed the molecular signature tag in metadata of an image file based on a captured image of the object by a camera of the electronic device.

Abstract: The disclosure includes methods of identifying a dog at risk of developing a an autoimmune disease or condition, for example a hypothyroid disease or condition, comprising testing whether the dog exhibits one or more selected single nucleotide polymorphisms (SNPs), together with diagnostic kits for carrying out such methods, methods of treatment or prophylaxis of such autoimmune disease or condition, e.g., comprising administering an effective amount of tea extract to a dog in need thereof, and a canine diet or supplement comprising tea extract, useful for treatment of prophylaxis of such autoimmune disease or condition, or for maintenance of thyroid health in a dog.

Abstract: The invention relates to anti-sigma factors (“anti-sigmas”) that bind to sigma factors and block activation of transcription. Anti-sigmas and their cognate sigma factors provide a highly effective mechanism for regulating gene expression in genetic circuits.

Abstract: A computer system aligns two or more sequences with each other to identify similarities and differences between the aligned sequences. The sequences may, for example, represent proteins. The system performs alignment quickly and accurately by representing the sequences as perceptual information and conceptual information having mappings between them in a knowledgebase, and then performing the alignment based on the representations of the sequences in the knowledgebase. The alignment may be performed in polynomial time, regardless of the number of sequences that are aligned.

Abstract: The disclosure provides modified biotin-binding proteins which can be expressed in soluble form in high yield in bacteria. Also provided are fusion proteins comprising the modified biotin-binding protein and an antigen. The disclosure further provides non-hemolytic variants of alpha-hemolysin from S. aureus and fusion protein comprising non-hemolytic variant of alpha-hemolysin and a biotin-binding domains. Immunogenic compositions comprising the proteins are also disclosed and use of such immunogenic compositions for inducing an immune response or for vaccinating a subject are also disclosed.

Abstract: The present invention, in one embodiment, provides a method of measuring pressure or temperature using a sensor including a sensor element composed of a plurality of carbon nanotubes. In one example, the resistance of the plurality of carbon nanotubes is measured in response to the application of temperature or pressure. The changes in resistance are then recorded and correlated to temperature or pressure. In one embodiment, the present invention provides for independent measurement of pressure or temperature using the sensors disclosed herein.

Abstract: Methods and systems of quantifying a target material in solution include detection of a size change of a hybridized nucleic acid complex, without the use of nanobeads. In particular, the examples include providing a plurality of nucleic acid fragments and a species-specific oligonucleotide tags, measuring the size of the nucleic acid fragments and/or oligonucleotides to predetermine a standard distribution of the solution(s), introducing the oligonucleotides in a solution containing nucleic acid target materials and/or non-target materials, and hybridizing the oligonucleotides with the species-specific target material if present in the solution. The size of the nucleic acid complexes in solution are then measured after hybridization, and the presence or non-presence of the species-specific target material is detected and/or quantified by comparing the measured size of the nucleic acid complexes after hybridization to the standard distribution.

Abstract: The present invention relates to an extracellular binding domain for an allosteric inhibitor, whereby said binding domain is derived from a single membrane span tyrosine kinase receptor. More specifically, the invention relates to an extracellular domain derived from a Fibroblast Growth Factor Receptor (FGFR). It further relates to the use of this domain for the identification of similar domains in the extracellular part of other tyrosine kinase receptors, and to a screening method for identification of a small compound allosteric inhibitor.

Abstract: A sample preparation and analysis system. The system includes a housing with a sample preparation station and a sample analysis station positioned within the housing. The sample analysis station is spaced away from the sample preparation station. A transport assembly is configured to move at least one sample within the housing and between the sample preparation station and the sample analysis station.

Abstract: The present application is directed to methods and systems for identifying small molecule compounds in mixtures using a library comprising calculated structures and corresponding calculated mass spectral fragmentation patterns of known and/or hypothetical small molecule compounds that may be in the mixture and screening of a mass spectrum of the mixture using the library to identify matching fragmentation patterns. If a mass spectral fragmentation pattern present in the mass spectrum of the mixture matches a calculated fragmentation pattern of one of the known or hypothetical compounds this confirms the identity of a compound in the mixture as the known or hypothetical compound. The method represents a platform method that can be used for a multitude of purposes related to the screening and identification of compounds in mixtures.

Abstract: Aspects of the invention provide methods for selecting a candidate oligonucleotide for activating expression of a target gene. Further aspects of the invention provide methods of selecting a set of oligonucleotides that is enriched in oligonucleotides that activate expression of a target gene. Further aspects provide single stranded oligonucleotides that modulate gene expression and compositions and kits comprising the same. Methods for modulating gene expression using the single stranded oligonucleotides are also provided.

Abstract: A method of modeling phase characteristics of thermodynamic systems utilizing pseudo-properties strategy and a reduced number of variables is disclosed herein. The method describes a means of determining the probability of phase splitting of mixtures of materials at a given temperature, pressure, and composition by characterizing the functions that describe the system via pseudo-properties, and also by describing the system in n?1 or fewer variables, where n represents the number of components in the system of interest. In an embodiment, a multi-component system is characterized in one variable, thereby providing simplified thermodynamic models in a time-efficient manner. In addition, the information generated by this reduced-variable calculation can further be used as a starting point for calculations of equations of state.

Abstract: This disclosure relates generally to the prediction of a gene target of an enhancer based on genomic proximity and a comparison to a set of known enhancer-gene pairs. A gene can be selected a gene from a given cell type. A domain can be established bi-directionally around the gene, and enhancers located within the domain can be identified. The enhancers located within the domain can be considered to be in close genomic proximity to the gene. For each enhancer, a test pair of the enhancer and the gene can be established and compared to a set of known enhancer-gene pairs. The prediction can be established based on the comparison and the genomic proximity.

Abstract: The present invention is directed to compositions and methods for the independent and unconstrained identification of attractor metagenes as surrogates of pure biomolecular events as well as the use of such attractor metagenes in performing medical diagnosis, prognosis, and developing appropriate therapeutic regimes.

Abstract: The present invention relates to novel short interfering RNA (siRNA) molecules that are multi-targeted. More specifically, the present invention relates to siRNA molecules that target two or more sequences. In one embodiment, multi-targeting siRNA molecules are designed to incorporate features of siRNA molecules and features of micro-RNA (miRNA) molecules. In another embodiment, multi-targeting siRNA molecules are designed so that each strand is directed to separate targets.

Abstract: The present invention relates to improved and integrated methods for the characterisation of an interaction site on a target protein that modulates the phenotype of a mammalian cell, such as a phenotype other than death and/or reduced growth. Such methods of the present invention include those to identify a target protein modulates such a phenotype of a mammalian cell, and optionally to characterise an interaction site on said target protein. Such identification and characterisation methods are useful in the development of research tools and/or therapeutics, such protein/peptide or small molecule therapeutics. Accordingly, the present invention also relates to methods of: identification of a ligand, such as a small molecule ligand, that binds to such a target protein; and identification a compound being a candidate modulator of said phenotype of a mammalian cell.

Abstract: Devices, systems, and methods for strain-specific identification and assessment of susceptibility of microorganisms based on the response of sensors in a colorimetric sensor array to metabolic products of the microorganism.

Abstract: This invention provides transgenic plant cells with recombinant DNA for expression of proteins that are useful for imparting enhanced agronomic trait(s) to transgenic crop plants. This invention also provides transgenic plants and progeny seed comprising the transgenic plant cells where the plants are selected for having an enhanced trait selected from the group of traits consisting of enhanced water use efficiency, enhanced cold tolerance, increased yield, enhanced nitrogen use efficiency, enhanced seed protein and enhanced seed oil. Also disclosed are methods for manufacturing transgenic seed and plants with enhanced traits.

Abstract: The disclosure provides a general method for the production of protein variants with a reduced aggregation propensity without affecting the thermodynamic stability of the variant with respect to the wild-type protein.

Abstract: The presently disclosed subject matter provides methods for improving the efficacy of a plant breeding program aimed at altering phenotypic traits for which associations with genetic markers can be established. Genome-wide genetic values of individuals are computed based on the individuals' marker genotypes and the associations established between genetic markers and phenotypic traits. Individuals and breeding schemes are then selected based both on the individuals' genome-wide genetic value and on the distributions of these genetic values for the potential progenies derived through the breeding schemes under evaluation. The presently disclosed subject matter also provides systems and computer program products for performing the disclosed methods as well as plants selected, provided, or produced by any of the methods herein and transgenic plants created by any of the methods herein.

Abstract: A new pipeline for the rational design and interpretation of biomarker panels is provided. The pipeline includes: generating the maximally informative marker set from biomarker databases; selecting an optimal biomarker panel based on the desired accuracy, economic, and experimental constraints; and interpreting the assay results by a statistically robust matching to reference data. The pipeline can also be used to identify biological samples, including cell types and progenitor cells.

Abstract: Gene expression analysis is generally performed on heterogeneous tissue samples consisting of multiple cell types. Current methods developed to separate heterogeneous gene expression rely on prior knowledge of the cell-type composition and/or signatures—these are not available in most public datasets. We present a novel method to identify the cell-type composition, signatures and proportions per sample without need for a priori information. The method was successfully tested on controlled and semi-controlled datasets and performed as accurately as current methods that do require additional information. As such, this method enables the analysis of cell-type specific gene expression using existing large pools of publically available microarray datasets.

Abstract: Various embodiments provide lossless compression of an enumeration space for genetic founder lines. In one embodiment, an input comprising a set of genetic founder lines and a maximum number of generations G is obtained. A set of genetic crossing templates of a height h is generated. A determination is made if at least a first genetic crossing template in the set of genetic crossing templates is redundant with respect to a second genetic crossing template in the set of genetic crossing templates. Based on the at least first genetic crossing template being redundant is redundant with respect to the second genetic crossing template, the at least first genetic crossing template is removed from the set of genetic crossing templates. This process of removing the at least first genetic crossing template from the set of genetic crossing templates the redundant creates an updated set of genetic crossing templates.

Abstract: The present invention generally relates to methods of rapidly and efficiently searching biologically-related data space. More specifically, the invention includes methods of identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. The invention also provides methods of modeling sequence-activity relationships. As many of the methods are computer-implemented, the invention additionally provides digital systems and software for performing these methods.

Abstract: Disclosed herein are computer-based systems, media and methods of generating dynamic classifiers and uses thereof. The dynamic classifiers may be generated from a subset of cases and/or a subset of genes that have a molecular similarity to a subject suffering from a cancer. Thus, the dynamic classifiers may be subject-specific. The dynamic classifiers may be used in the diagnosis, prognosis and/or monitoring of a status or outcome of a cancer in a subject in need thereof.

Abstract: Certain embodiments provide a method for crystallizing a GPCR. The method may employ a fusion protein comprising, from N-terminus to C-terminus: a) a first portion of a family C G-protein coupled receptor (GPCR), wherein the first portion comprises the TM1, TM2 and TM3, regions of the GPCR; b) a stable, folded protein insertion; and c) a second portion of the GPCR, wherein the second portion comprises the TM4, TM5 TM6 and TM7 regions of the GPCR.