Abstract: Tools for diagnosis and management of patients suspected of having or having been previously diagnosed with systemic sclerosis are based on the determination one or more of the markers described herein, specifically, the markers having the amino acid sequence of SEQ ID NOS: 1-62 and 66-76 in a sample from the subject. Specific marker ratios and subsets of markers and ratios identify a patient and further subclassify the patient. The information may be used prospectively to study the response of subclassified patients to existing or novel therapeutic strategies.

Abstract: Methods and systems for evaluating genomic sequences are described. The methods include approaches for evaluating the prevalence of genomes in a sample based on the prevalence of segments in the sample, and may additionally rely on the prevalence of segments in reference genomes and an estimated genome population distribution of the sample.

Abstract: The multifunctional medical device contains system on chip (SoC) computation functionality to organize several functional modules consisting of analytical, diagnostic and therapeutic tasks in the microfluidic assembly. Micro-valves, micro-tubes, micro-wires and gates organize the chambers of the flexible modules which hold multiple chemical and biological agents for combination on demand.

Abstract: The system presents applications of personalized medicine with intelligent medical devices (iMDs) and customizes therapies to complex problems involving neurological, cardiovascular, cancer, immunological and endocrinological diseases.

Abstract: Methods, systems, and apparatus for accurately determining a proportion (ratio) of two analytes is provided, as well as provide a concentration of a first analyte from a determined concentration of a second analyte and from a proportion of the analytes to each other. In one aspect, a surface model (called a “dose surface” herein) relating the concentrations of the two analytes to the proportion can be used to obtain accurate values for one of the variables (e.g. a concentration or the proportion) when the other two variables have previously been obtained. The dose surface can be a three-dimensional surface and be non-linear. The dose surface model can include multiple regression functions. For example, measured responses can be individually converted to concentrations using two dose-response curves, and the concentrations can be input to a dose surface function to obtain the proportion.

Abstract: Methods and systems for assessing the probabilities of the expression of one or more traits in progeny are described.

Abstract: Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.

Abstract: Mapping oligomer sequences includes receiving a set of related oligomer sequences, applying one or more key patterns derived from a set of oligomer sequence relationships to obtain one or more keys that are consistent with the set of related oligomer sequences, and locating the one or more keys in an index configured to map a plurality of possible keys to their respective candidate and/or validated locations in a reference.

Abstract: An automated analyzer for performing multiple diagnostic assays simultaneously includes multiple stations in which discrete aspects of the assay are performed on fluid samples contained in sample vessels. The analyzer includes stations for automatically preparing a sample, incubating the sample, preforming an analyte isolation procedure, ascertaining the presence of a target analyte, and analyzing the amount of a target analyte. An automated receptacle transporting system moves the sample vessels from one station to the next. A method for performing an automated diagnostic assay includes an automated process for isolating and amplifying a target analyte, and, in one embodiment, a method for real-time monitoring of the amplification process.

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

Abstract: The present disclosure provides systems and methods for nucleic acid sequence analysis. A system for processing raw nucleic acid sequence data from a genomic sequencer comprises a data processing server having a housing contained therein one or more processing modules. The one or more processing modules can each comprise an electronic control unit programmed to align nucleic acid sequence data from a genomic sequencing device and perform one or more of variant analysis and structural variant analysis on the nucleic acid sequence data. The system can further comprise a computer server in communication with the processing server. The computer server can be programmed or otherwise configured to process and/or analyze the aligned nucleic acid sequence data.

Abstract: A method for proteomic analysis of a biological sample is disclosed, which includes obtaining peptide sequences of proteins in a target list; and identifying proteins in the biological sample by mapping the obtained peptide sequences on proteins in a proteomic database, wherein the target list is determined using information of RNA transcripts in the biological sample and/or the target list is determined using information of RNA transcripts in the biological sample. The peptide sequences are determined using a mass spectrometer. The mapping is performed on a subset of proteins based on the information of RNA transcripts.

Abstract: The invention provides methods and compositions, including, without limitation, algorithms, computer readable media, computer programs, apparatus, and systems for determining the identity of nucleic acids in nucleotide sequences using, for example, data obtained from sequencing by synthesis methods. The methods of the invention include correcting one or more phenomena that are encountered during nucleotide sequencing, such as using sequencing by synthesis methods. These phenomena include, without limitation, sequence lead, sequence lag, spectral crosstalk, and noise resulting from variations in illumination and/or filter responses.

Abstract: Electronic label processor compares bioinformatic values to determine pharmaco-genomic mutation associated with host. Label display indicates pharmaco-genomic mutation, which is network-accessible for modified medical message. Bioinformatic values are determined preferably at different times.

Abstract: Systems, methods and apparatus for an automated analysis of a collection of melt curves is provided. The analysis can identify certain characteristics of double stranded nucleotide sequences (e.g. DNA or other nucleotide sequences) which were melted. For example, a variation (e.g. a mutation) in the sequences (also called amplicons) may be determined from the analysis. The amplicons may be amplified via any amplification mechanism, such as PCR or Ligase chain reaction (LCR). The automated analysis can include identifying a melt region, normalizing a melt curve, and clustering melt curves.

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

Abstract: The present invention provides a method capable of detecting single or multiple fetal chromosomal aneuploidies in a maternal sample comprising fetal and maternal nucleic acids, and verifying that the correct determination has been made. The method is applicable to determining copy number variations (CNV) of any sequence of interest in samples comprising mixtures of genomic nucleic acids derived from two different genomes, and which are known or are suspected to differ in the amount of one or more sequence of interest. The method is applicable at least to the practice of noninvasive prenatal diagnostics, and to the diagnosis and monitoring of conditions associated with a difference in sequence representation in healthy versus diseased individuals.

Abstract: The invention relates to methods based on the quantification of a set of biomarkers, preferably in biological samples isolated from skeletal muscle, for performing the diagnosis, prognosis and/or monitoring of muscular degeneration, preferably muscular degeneration caused by motor neuron diseases, more preferably amyotrophic lateral sclerosis (ALS); and to a kit for the diagnosis, prognosis and monitoring of said type of diseases. The method in the invention for the prognosis and/or monitoring of muscular degeneration makes it possible to determine the rate of progression of said degeneration (fast or slow rate of progression in relation to the normal rate of progression).

Abstract: Exemplary systems, methods and computer-accessible mediums for assembling at least one haplotype or genotype sequence of at least one genome can be provided, which can include, obtaining a plurality of randomly located sequence reads, incrementally generating overlap relations between the randomly located sequence reads using a plurality of overlapper procedures, and generating a layout of some of the randomly located short sequence reads based on a function in combination with constraints based on information associated with the one genome while substantially satisfying the constraints. The score-function can be derived from overlap relations between the randomly located short sequence reads. A search can be performed together with score- and constraint-dependent pruning to determine the layout substantially satisfying the constraints. A part of the genome wide haplotype sequence or the genotype sequence of the genome can be generated based on the overlap relations and the randomly located sequence reads.

Abstract: Methods for interpreting absolute copy number of complex tumors and for determining the copy number of a genomic region at a detection position of a target sequence in a sample are disclosed. In certain aspects, genomic regions of a target sequence in a sample are sequenced and measurement data for sequence coverage is obtained. Sequence coverage bias is corrected and may be normalized against a baseline sample. Hidden Markov Model (HMM) segmentation, scoring, and output are performed, and in some embodiments population-based no-calling and identification of low-confidence regions may also be performed. A total copy number value and region-specific copy number value for a plurality of regions are then estimated.

Abstract: A bio sensing meter for determining the presence of an analyte in a biological sample. The meter's operation is controlled by a code provided by a removably pluggable coding module for receiving a sample strip. The coding module defines at least one code. The code ciphers at least one parameter value that is employed in controlling the operation of said meter, for example by controlling the execution of an algorithm performed by the meter that enables determination of an analyte concentration value. The at least one code is represented by at least one electrical component having a determined characteristic, preferably a resistance.

Abstract: Apparatus and methods for practicing telemedicine in the form of software systems acting over a network and kits containing laboratory supplies and equipment to organize the laboratory operations and interpret the results of molecular diagnostic testing are disclosed. At least two computers in communication over the Internet or other network are used, a remote computer located at a remote site and a central server located at a central site. The remote site may be geographically distant from the central site. A specimen is procured from a patient proximate to the remote site. Laboratory operations are conducted on the specimen at the remote site. The laboratory data resulting from the laboratory operations is interpreted by an expert reviewer who may be located at the central site, and a report is then transmitted back to the remote site.

Abstract: Disclosed are new and improved methods and systems for nucleic acid sequence analysis that can analyze data indicative of natural by-products of nucleotide incorporation events without the need for exogenous labels or dyes to identify nucleic acid sequences of interest. In particular, the methods and systems of the present teachings can process such data and various forms thereof to align fragments of the nucleic acid(s) of interest, particularly those analyzed using an addition sequencing technique, for example, as occurs with the use of nucleotide flows.

Abstract: Methods and materials are provided for determining the responsiveness of a subject to a therapy, such as an antibody therapy and for selecting and/or for treating a subject based on a Fc?RIIA polymorphism, or a Fc?RIIIA polymorphism, or both an Fc?RIIA polymorphism and a Fc?RIIIA polymorphism, including where the treatment is an therapy, such as rituximab. Methods and materials are also provided for designing, making, screening, testing and/or administering antibodies as well as for optimizing antibody therapies based upon a subject's Fc?RIIA polymorphism, or Fc?RIIIA polymorphism, or both the Fc?RIIA polymorphism and the Fc?RIIIA polymorphism.

Abstract: The present invention provides processes for calculating phased genomic sequences of the fetal genome using fetal DNA obtained from a maternal sample. The processes and systems of the present invention utilize novel technological and computational approaches to detect fetal genomic sequences and determine the phased heritable genomic sequences. The invention could be used, e.g., to identify in utero deleterious mutations carried by the parents and inherited by a fetus within a particular heritable genomic region.

Abstract: An embodiment of a method for generating a flow order that minimizes the accumulation of phasic synchrony error in sequence data is described that comprises the steps of: (a) generating a plurality of sequential orderings of nucleotides species comprising a k-base length, wherein the sequential orderings define a sequence of introduction of nucleotide species into a sequencing by synthesis reaction environment; (b) simulating acquisition of sequence data from one or more reference genomes using the sequential orderings, wherein the sequence data comprises an accumulation of phasic synchrony error; and (c) selecting one or more of the sequential orderings using a read length parameter and an extension rate parameter.

Abstract: Systems and methods for analyzing genetic sequence data involve: (a) obtaining, by a computer system, genetic sequencing data pertaining to a subject; (b) splitting the genetic sequencing data into a plurality of segments; (c) processing the genetic sequencing data such that intra-segment reads, read pairs with both mates mapped to the same data set, are saved to a respective plurality of individual binary alignment map (BAM) files corresponding to that respective segment; (d) processing the genetic sequencing data such that inter-segment reads, read pairs with both mates mapped to different segments, are saved into at least a second BAM file; and (e) processing at least the first plurality of BAM files along parallel processing paths. The plurality of segments may correspond to any given number of genomic subregions and may be selected based upon the number of processing cores used in the parallel processing.

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

Abstract: Methods, systems, and apparatus determine whether a first chromosomal region exhibits a deletion or an amplification associated with cancer in a sample from a subject (e.g., where the sample includes a mixture of cell-free DNA from tumor cells and non-malignant cells. Nucleic acid molecules of the biological sample are sequenced. Respective amounts of a clinically-relevant chromosomal region and of background chromosomal region(s) are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether first chromosomal region exhibits a deletion or an amplification associated with cancer.

Abstract: A computer implemented method for characterizing one or more sequences by generating index values representing portions of the sequences and finding characterizing index values based on a comparison of the index values. The index values may be obtained by applying one or more mask over each sequence. The modified masks may have associated weightings and index values obtained using modified masks may be retained in the index only if the weightings are above a threshold value. Characterising index values may also be assessed for for their degree of uniqueness. Characterizing indexes may be used for predicting correlation between a sample sequence and one or more reference sequences. Biological monitoring systems utilising the characterizing index values are also disclosed. A biological indicator may be generatgenerated using one or more characterizing index values obtained by the above method and be used to produce an indicator that undergoes a property change in the presence of the one or more sequence.

Abstract: Methods using mass spectral data analysis and a classification algorithm provide an ability to determine whether a non-small-cell lung cancer patient, head and neck squamous cell carcinoma or colorectal cancer patient has likely developed a non-responsiveness to treatment with a drug targeting an epidermal growth factor receptor pathway. As the methods of this disclosure require only simple blood samples, the methods enable a fast and non-intrusive way of measuring when drugs targeting the EGFR pathway cease to be effective in certain patients. This discovery represents the first known example of true personalized selection of these types of cancer patients for treatment using these classes of drugs not only initially, but during the course of treatment.

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

Abstract: A method, computer product and computer system of transmitting a compressed genome of an organism: a computer at a source reading an uncompressed sequence and a reference genome from a repository; the computer comparing nucleotides of the genetic sequence of the organism to nucleotides from a reference genome, to find differences where nucleotides of the genetic sequence of the organism which are different from the nucleotides of the reference genome; the computer using the differences to create surprisal data, the surprisal data comprising a starting location of the differences within the reference genome, and the nucleotides from the genetic sequence of the organism which are different from the nucleotides of the reference genome; and the computer transmitting, to a destination, a compressed genome comprising: surprisal data and an indication of the reference genome, discarding sequences of nucleotides that are the same in the sequence of the organism and reference genome.

Abstract: Personalized medicine involves the use of a patient's molecular markers to guide treatment regimens for the patient. The scientific literature provides multiple examples of correlations between drug treatment efficacy and the presence or absence of molecular markers in a patient sample. Methods are provided herein that permit efficient dissemination of scientific findings regarding treatment efficacy and molecular markers found in patient tumors to health care providers.

Abstract: In an embodiment of the present invention, a modified version of the PHASE model is implemented that is substantially more accurate than the FastPHASE model. Modifications in an embodiment of the present invention include using a parameterization EM algorithm similar to that of the FastPHASE model, and to perform optimization on haplotypes rather than MCMC sampling. In an embodiment, the imputed haplotypes themselves are used as hidden states in the HMM because this is believed to be important for the PHASE model's accuracy. This increase in accuracy becomes more pronounced with increasing sample size. This difference is attributed to the PHASE model's likelihood which produces long, shared haplotypes between pairs of individuals.

Abstract: Polymorphic variants that have been found to be associated with risk of urinary bladder cancer are provided herein. Such polymorphic markers are useful for diagnostic purposes, such as in methods of determining a susceptibility, and for prognostic purposes, including methods of predicting prognosis and methods of assessing an individual for probability of a response to therapeutic 5 agents, as further described herein. Further applications utilize the polymorphic markers of the invention include screening and genotyping methods. The invention furthermore provides related kits, and computer-readable media and apparatus.

Abstract: The methods and apparatus 100 disclosed herein concern DNA sequencing. In some embodiments of the invention, the methods comprise measuring the distance between labeled nucleotides 220, such as nucleotides labeled with bulky groups. The methods may further comprise placing identical template DNA 200 into four reaction chambers 110, 120, 130, 140, each containing a different labeled nucleotide precursor, synthesizing complementary strands 230, 240, 250 and detecting labeled nucleotides 220. The distances between labeled nucleotides 220 may be used to construct 450 distance maps 310, 320, 330, 340 for each type of labeled nucleotide 220. The distance maps 310, 320, 330, 340 may be aligned 520 to obtain a nucleic acid sequence 210. Overlapping data analysis and frequency analysis may be used to construct 450 the distance maps 310, 320, 330, 340 and non-overlapping data analysis may be used to align 520 the distance maps into a sequence 210.

Abstract: A computer system for rank normalization for differential expression analysis of transcriptome sequencing data includes a processor; and a memory comprising a first dataset comprising transcriptome sequencing data, the first dataset comprising a plurality of genes and a respective ranking value associated with each of the plurality of genes, the system configured to perform a method including assigning a rank to each of the genes of the plurality of genes based on the ranking value to produce a first rank normalized dataset; determining a change between a first rank of a particular gene in the first rank normalized dataset, and a second rank of the particular gene in a second rank normalized dataset, the second rank normalized dataset being based on a second dataset comprising transcriptome sequencing data; and determining whether the particular gene is differentially expressed between the first and second datasets based on the determined change in rank.

Abstract: Compositions and methods are provided for a rapid, high-resolution, high-throughput method for determining the intramolecular interactions between the nucleotides present in an polynucleotide, such that single-stranded nucleotides, and nucleotides in a double-stranded configuration are distinguished and identified. Tertiary contacts and solvent accessible regions may also be determined, where such contacts and regions may result from a single stranded configuration, intermolecular interactions with other macromolecules including, without limitation, DNA, protein, RNA, etc.; intermolecular interactions with small molecules which may include drug candidates; or a combination of macromolecules and small molecules.

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

Abstract: A computer-implemented method for rank normalization for differential expression analysis of transcriptome sequencing data includes receiving, by a computer, a first dataset comprising transcriptome sequencing data, the first dataset comprising a plurality of genes, and further comprising a respective ranking value associated with each of the plurality of genes; assigning a rank to each of the genes of the plurality of genes based on the ranking value to produce a first rank normalized dataset; determining a change between a first rank of a particular gene in the first rank normalized dataset, and a second rank of the particular gene in a second rank normalized dataset, the second rank normalized dataset being based on a second dataset comprising transcriptome sequencing data; and determining whether the particular gene is differentially expressed between the first dataset and the second dataset based on the determined change in rank.

Abstract: The systems and methods described herein utilize a probabilistic modeling framework for reverse engineering an ensemble of causal models, from data and then forward simulating the ensemble of models to analyze and predict the behavior of the network. In certain embodiments, the systems and methods described herein include data-driven techniques for developing causal models for biological networks. Causal network models include computational representations of the causal relationships between independent variables such as a compound of interest and dependent variables such as measured DNA alterations, changes in mRNA, protein, and metabolites to phenotypic readouts of efficacy and toxicity.

Abstract: A system for processing information for providing semantic information and/or information associated with the semantic information useful for each individual organism through effective utilization of differences in nucleotide sequence-related information among individual organisms is constructed. The method for processing information on a nucleotide sequence comprises: (a) receiving request information for an object and/or service; (b) obtaining positional information in accordance with the request information from a memory having positional information representing a position in a nucleotide sequence memorized therein; and (c) obtaining nucleotide sequence-related information corresponding to the positional information obtained in (b) above, and obtaining semantic information implied by the nucleotide sequence-related information and/or information associated with the semantic information.

Abstract: Each of a plurality of substantially co-linear alignments has a score. Each alignment may comprise a starting alignment that has been diagonally extended to meet a length requirement. Dynamic programming is performed in interalignment regions between the extended alignments to generate a corresponding set of interalignment scores. Alignment scores and interalignment scores are summed to generate a score for the entire chain of alignments. This process is repeated for multiple chains. Chains of alignments are ranked by chain score and are displayed to a user. In one embodiment, additional dynamic programming is performed at the head and tail of each chain to increase the chain score when possible. An integrated circuit that performs the method at high speed in hardware is disclosed. Techniques are disclosed that reduce the amount of interalignment dynamic programming. The method increases sensitivity and gives an order of magnitude speed improvement over NCBI-BLAST.

Abstract: Disclosed are methods, systems, and apparatuses for the measurement of hybridization of nucleic acid polymers or binding other biological molecular species such as proteins, enzymes, receptors, and antibodies to binding partners, by backscattering interferometry (BSI).

Abstract: This invention provides a quantitative method to determine transcriptionally active regions and quantify sequence abundance from large scale sequencing data. The invention also provides a system based on reference sequences to design and implement the method. The system processes large scale sequence data from high throughput sequencing, generates transcriptionally active region sequences as necessary, and quantifies the sequence abundance of the gene or transcriptionally active region. The method and system are useful for many analyses based on RNA expression profiling.

Abstract: A computer implemented method for generating nucleotide sequences containing candidate homing endonuclease genes (HEGs). A search is performed in a database stored on a storage medium of nucleotide sequences for amino acid sequences having a subsequence having a homology level with the translation of a subsequence of one or more predetermined HEGs. For each amino acid sequence generated by the search, one or more nucleotide sequences are retrieved encoding the amino acid sequence. The results of this search used in a second search of a database stored on a storage medium to generate the HEG containing sequences.

Abstract: A method for determining an allelic ladder signal for DNA analysis includes obtaining a measured allelic ladder signal for an allelic ladder substance, which includes a plurality of fragments, obtaining a reference set of expected fragment sizes of fragments of the ladder substance, and generating a signal identifying whether a peak for a fragment size of the measured ladder signal is a true peak of the ladder substance based on the reference set of expected fragment sizes, wherein the allelic ladder signal for DNA analysis includes the true peaks identified in the signal.

Abstract: The invention discloses genetic variants that have been determined to be susceptibility variants of thyroid cancer. Methods of disease management, including methods of determining susceptibility to thyroid cancer, methods of predicting response to therapy and methods of predicting prognosis of thyroid cancer using such variants are described. The invention further relates to kits useful in the methods of the invention.

Abstract: Systems and method for identifying somatic mutations can receive first ans second sequence information, determine if a variant present in the first sequencing information is also present in the second sequence information, and identify variants present in the first sequence information are somatic mutations when the variant is either not present in the second sequence information or the presence of the variant in the second sequence information is likely due to a sequencing error.