Abstract: Provided are methods of treating a patient diagnosed with Fabry disease and methods of enhancing ?-galactosidase A in a patient diagnosed with or suspected of having Fabry disease. Certain methods comprise administering to a patient a therapeutically effective dose of a pharmacological chaperone for ?-galactosidase A, wherein the patient has a mutation in the nucleic acid sequence encoding ?-galactosidase A. Also described are uses of pharmacological chaperones for the treatment of Fabry disease and compositions for use in the treatment of Fabry disease.

Abstract: Method and systems for preparing and analyzing a DNA sample from a subject are provided herein. Also provided are methods and systems for obtaining, analyzing, and manipulating genomic and proteomic sequence data. In particular, methods and systems provided herein involve transformation of raw genetic or proteomic sequence into a compressed data set and transmission of the compressed data set using a fixed binary encoding scheme capable of compressing the data by up to 75%. An interface is in communication with the compression module and configured to display transmitted genomic and proteomic sequence data.

Abstract: Disclosed herein are methods and compositions for associating a genetic variant with intraretinal fluid. Also disclosed herein are methods and compositions for associating a genetic variant with visual acuity, anatomic outcomes or treatment frequency.

Abstract: The invention provides a method for determining copy number variations (CNV) of a sequence of interest in a test sample that comprises a mixture of nucleic acids that are known or are suspected to differ in the amount of one or more sequence of interest. The method comprises a statistical approach that accounts for accrued variability stemming from process-related, interchromosomal and inter-sequencing variability. The method is applicable to determining CNV of any fetal aneuploidy, and CNVs known or suspected to be associated with a variety of medical conditions. CNV that can be determined according to the method include trisomies and monosomies of any one or more of chromosomes 1-22, X and Y, other chromosomal polysomies, and deletions and/or duplications of segments of any one or more of the chromosomes, which can be detected by sequencing only once the nucleic acids of a test sample.

Abstract: Technology provided herein relates in part to non-invasive classification of one or more genetic copy number variations (CNVs) for a test sample. Technology provided herein is useful for classifying a genetic CNV for a sample as part of non-invasive pre-natal (NIPT) testing and oncology testing, for example.

Abstract: The invention relates to assembly of sequence reads. The invention provides a method for identifying a mutation in a nucleic acid involving sequencing nucleic acid to generate a plurality of sequence reads. Reads are assembled to form a contig, which is aligned to a reference. Individual reads are aligned to the contig. Mutations are identified based on the alignments to the reference and to the contig.

Abstract: A method for sequencing a nucleic acid template includes: (a) performing a first sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a first predetermined ordering of nucleotides and/or reagents to obtain a first sequencing result; (b) after the first sequencing process, performing a second sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a second predetermined ordering of nucleotides and/or reagents to obtain a second sequencing result, the second predetermined ordering of nucleotides and/or reagents being different from the first predetermined ordering of nucleotides and/or reagents and at least one of the first and second predetermined orderings of nucleotides and/or reagents being designed for repeat sequencing; and (c) determining a sequence of bases corresponding to at least a portion of the nucleic acid template using both the first sequencing result and the second sequencing result.

Abstract: Methods for estimating genomic copy number and loss of heterozygosity using Hidden Markov Model based estimation are disclosed.

Abstract: A method for evaluating variant likelihood includes: providing a plurality of template polynucleotide strands, sequencing primers, and polymerase in a plurality of defined spaces disposed on a sensor array; exposing the plurality of template polynucleotide strands, sequencing primers, and polymerase to a series of flows of nucleotide species according to a predetermined order; obtaining measured values corresponding to an ensemble of sequencing reads for at least some of the template polynucleotide strands in at least one of the defined spaces; and evaluating a likelihood that a variant sequence is present given the measured values corresponding to the ensemble of sequencing reads, the evaluating comprising: determining a measurement confidence value for each read in the ensemble of sequencing reads and modifying at least some model-predicted values using a first bias for forward strands and a second bias for reverse strands.

Abstract: We describe systems and methods for generating and training convolutional neural networks using biological sequences and relevance scores derived from structural, biochemical, population and evolutionary data. The convolutional neural networks take as input biological sequences and additional information and output molecular phenotypes. Biological sequences may include DNA, RNA and protein sequences. Molecular phenotypes may include protein-DNA interactions, protein-RNA interactions, protein-protein interactions, splicing patterns, polyadenylation patterns, and microRNA-RNA interactions, which may be described using numerical, categorical or ordinal attributes. Intermediate layers of the convolutional neural networks are weighted using relevance score sequences, for example, conservation tracks.

Abstract: Processes and materials to detect cancer from a biopsy are described. In some cases, cell-free nucleic acids can be sequenced, and the sequencing result can be utilized to detect sequences derived from a neoplasm. Detection of somatic variants occurring in phase can indicate the presence of cancer in a diagnostic scan and a clinical intervention can be performed.

Abstract: Amino acid sequences of antibodies can be generated using a generative adversarial network that includes a first generating component that generates amino acid sequences of antibody light chains and a second generating component generates amino acid sequences of antibody heavy chains. Amino acid sequences of antibodies can be produced by combining the respective amino acid sequences produced by the first generating component and the second generating component. The training of the first generating component and the second generating component can proceed at different rates. Additionally, the antibody amino acids produced by combining amino acid sequences from the first generating component and the second generating component may be evaluated according to complentarity-determining regions of the antibody amino acid sequences.

Abstract: Techniques for determining one or more cell composition percentages from expression data. The techniques include obtaining expression data for a biological sample, the biological sample previously obtained from a subject, the expression data including first expression data associated with a first set of genes associated with a first cell type; determining a first cell composition percentage for the first cell type using the expression data and one or more non-linear regression models including a first non-linear regression model, wherein the first cell composition percentage indicates an estimated percentage of cells of the first cell type in the biological sample, wherein determining the first cell composition percentage for the first cell type comprises: processing the first expression data with the first non-linear regression model to determine the first cell composition percentage for the first cell type; and outputting the first cell composition percentage.

Abstract: The present disclosure describes methods for determining the functional consequences of mutations. The methods include the use of machine learning to identify and quantify features of all atom molecular dynamics simulations to obtain the disruptive severity of genetic variants on molecular function.

Abstract: Systems and methods for analyzing overlapping sequence information can obtain first and second overlapping sequence information for a polynucleotide, align the first and second sequence information, determine a degree of agreement between the first and second sequence information for a location along the polynucleotide, and determine a base call and a quality value for the location.

Abstract: Provided herein are methods, processes and apparatuses for non-invasive assessment of genetic variations.

Abstract: Systems, methods, and analytical approaches for short read sequence assembly and for the detection of insertions and deletions (indels) in a reference genome. A method suitable for software implementation is presented in which indels may be readily identified in a computationally efficient manner.

Abstract: The technology disclosed relates to determining pathogenicity of nucleotide variants. In particular, the technology disclosed relates to specifying a particular amino acid at a particular position in a protein as a gap amino acid, and specifying remaining amino acids at remaining positions in the protein as non-gap amino acids. The technology disclosed further relates to generating a gapped spatial representation of the protein that includes spatial configurations of the non-gap amino acids, and excludes a spatial configuration of the gap amino acid, and determining a pathogenicity of a nucleotide variant based at least in part on the gapped spatial representation, and a representation of an alternate amino acid created by the nucleotide variant at the particular position.

Abstract: The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

Abstract: Embodiments are directed to systems and methods for pathogen detection using next-generation sequencing (NGS) analysis of a sample. Embodiments may apply alignment algorithms (e.g., SNAP and/or RAPSearch alignment algorithms) to align individual sequence reads from a sample in a next-generation sequencing (NGS) dataset against reference genome entries in a classified reference genome database. Embodiments of the present invention may include classifying, filtering, and displaying results to a clinician that can then quickly and easily obtain the results of the sequencing to identify a pathogen or other genetic material in a sample that is being tested. A negative sample and a corresponding database can be used to remove contaminants from a list of candidate pathogens. Thus, embodiments are directed to a system that is configured to filter the results of a sequencing alignment and classify a sample quickly.