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 and apparatus for searching compressed nucleic acid sequences are disclosed. In the method, a reference sequence is compared with a subject sequence to be encoded, the subject sequence is compressed, an index is created with respect to the reference sequence and the compressed subject sequence, a position corresponding to a query is searched for in the compressed subject sequence using the index, a character found at the position within the compressed sequence is converted into a sequence, and the sequence is output as the response to the query.

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 present disclosure provides methods and systems for determining the presence or absence of aneuploidy in a fetus. In particular, the present disclosure provides noninvasive methods and systems for detecting the presence of fetal trisomy and other fetal chromosomal anomalies, paternity of a fetus and fetal genotype.

Abstract: A system for identifying connections between perturbagens and genes associated with a skin hyperpigmentation condition. The system includes a computer readable medium having a plurality of instances stored thereon, and a skin hyperpigmentation-relevant gene expression signature. Each instance includes an instance list of rank-ordered identifiers of differentially expressed genes, and the hyperpigmentation-relevant gene expression signature includes a gene expression signature list of identifiers representing differentially expressed genes associated with a hyperpigmentation condition or differentially expressed genes associated with a benchmark skin-lightening agent.

Abstract: Provided is a method of genome-wide testing of gene copy number at the genetically most important loci to determine whether the gene and/or its selected larger surrounding chromosome region is rearranged to result in an unbalanced abnormality in one or more subjects. The method includes selecting multiple gene loci of the DNAs to be examined in the test, conducting the test, and comparing the number of copies at each locus tested by quantification of total gene target number to determine the relative number of each polymorphic sequence detected to assure that each important tested sequence is distinguished from the other alleles at the same locus. A method of detecting the highest number of abnormal patients possible based upon the number of test sites available in a protocol is also provided. Depending upon the state of the life cycle, both of the methods can be done together or in sequence.

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: Polymorphic variants (e.g., certain alleles of polymorphic markers) that have been found to be associated with high blood eosinophil counts, conditions causative of eosinophilia (e.g., asthma, myocardial infarction), and/or hypertension are provided herein. Such polymorphic markers are useful for diagnostic purposes, such as in methods of determining a susceptility, and for prognostic purposes, including methods of predicting prognosis and methods of assessing an individual for probability of a response to a therapeutic agent, as further described herein. Further applications utilize the polymorphic markers of the invention include, screening methods and genotyping methods. The invention furthermore provides related kits, computer-readable medium, and apparatus.

Abstract: Improved compositions, methods, apparatus, and kits for high-throughput nucleic acid amplification, detection and sequencing are disclosed. A nucleic acid cluster having an identifiable center is produced by generating on a solid support an immobilized nucleic acid complement from a template, one of which comprises a detectable label; and amplifying the complement and the template to obtain a nucleic acid cluster on the support, the cluster having a substantially central location marked by the detectable label and a surrounding region comprising immobilized copies. Also disclosed are nucleotide sequence determination in nucleic acid clusters so produced, center position annotation in the clusters, assignment of sequence information to overlapping clusters, and related compositions and methods.

Abstract: Gamete donor selection includes receiving a specification including a phenotype of interest, receiving a genotype of a recipient and a plurality of genotypes of a respective plurality of donors, determining statistical information pertaining to the phenotype of interest based at least in part on different pairings of the genotype of the recipient and a genotype of a donor in the plurality of donors, and identifying a preferred donor among the plurality of donors, based at least in part on the statistical information determined.

Abstract: Methods for generating a normalized expression signal for microarray data based on a theoretical distribution at the unit level to produce a normalized expression signal for the single microarray that is independent of other microarrays. The method typically includes receiving microarray data representing a plurality of probe pairs for a single microarray, determining, for each probe pair, differences between intensities of perfect match (PM) probes and intensities of mismatched (MM) probes, determining a difference signal, D, based on the determined differences, and scaling the difference signal, D, to produce an expression signal, DS. The method also typically includes normalizing the expression signal based on a theoretical distribution at the unit level to produce a normalized expression signal for the single microarray that is independent of other microarrays.

Abstract: This invention provides several ways of managing GC bias that occurs during seequencing and analysis of genomic DNA. Maternal plasma can be used as a source of fetal DNA for analysis. DNA segments or tags obtained from the plasma can be aligned with a chromosomal region of interest and with an artificial reference chromosome assembled from regions of the genome having matching GC content.

Abstract: The present invention relates to a kit for diagnosing hepatocellular carcinoma consisting of plasma microRNA, a kit containing the same, and a new method therefor. The marker for diagnosing hepatocellular carcinoma consists of a plurality of nucleic acid molecules, each nucleic acid molecule encoding at least one microRNA sequence, preferably consists of nucleic acid molecules encoding hsa-miR-122, hsa-miR-192, hsa-miR-21, hsa-miR-223, hsa-miR-26a, hsa-miR-27a, hsa-miR-801 and hsa-miR-1228. The kit can be used for diagnosing hepatocellular carcinoma, especially early hepatocellular carcinoma, and also for discriminating plasma of at least one hepatocellular carcinoma patient from that of at east one healthy individual, at east one chronic hepatitis B patient, or at east one cirrhosis patient.

Abstract: A fractional concentration of clinically-relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments at multiple sizes. For example, the fractional concentration of fetal DNA in maternal plasma or tumor DNA in a patient's plasma can be determined. The size of DNA fragments in a sample is shown to be correlated with a proportion of fetal DNA and a proportion of tumor DNA, respectively. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a size parameter and the fractional concentration of the clinically-relevant DNA. For a given sample, a first value of a size parameter can be determined from the sizes of DNA fragments in a sample. A comparison of the first value to the calibration data points can provide the estimate of the fractional concentration of the clinically-relevant DNA.

Abstract: A method for calculating a sample size for a clinical trial of a first treatment can be provided. The method can include reading a survival curve from a clinical trial for a second treatment, wherein the clinical trial may be selected by a user interacting with a user interface. The method can further include selecting a plurality of points on the survival curve and storing coordinates for each of the plurality of points, wherein the plurality of points are selected so as to capture substantial features of the survival curve. Then, a hazard curve is generated based on the coordinates that were stored, wherein the hazard curve may be a step function. The method can further include calculating a sample size for the clinical trial of the first treatment using a Markov model based on the hazard curve.

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: Method of identifying a microRNA-recognition element and of generating microRNAs are disclosed. System and computer programs for performing such methods are disclosed. Recombinant nucleic acid molecule comprising a heterologous coding sequences and one or more MREs are also disclosed as are isolated nucleic acid molecule comprising one or more MRE sequences and being free of a coding sequence operably linked to regulatory elements. MicroRNA generated by a methods of the invention and the use of the microRNAs to downregulate gene expression are disclosed.

Abstract: According to embodiments, techniques for selecting a consistent part of a signal, including a photoplethysmograph (PPG) signal, are disclosed. A pulse oximetry system including a sensor or probe may be used to obtain a PPG signal from a subject. Signal peaks may be identified in the PPG signal. Characteristics of the signal peaks, including the amplitude levels of the signal peaks and/or the time-distance between the signal peaks may be used to determine if the PPG signal is consistent. In an embodiment, signal peaks are processed based on a consistency metric, and the processed signal peaks are compared to the consistency metric to determine if the PPG signal is consistent. If the PPG signal is determined to be consistent, the PPG signal may be further analyzed to determine an underlying signal parameter, including, for example, a patient respiration rate.

Abstract: Disclosed herein are kits, compositions, and methods relating to the classification of samples. Methods disclosed herein can be used to identify sample mix-ups. Methods disclosed herein can also be used to diagnose conditions or to support treatment-related decisions.

Abstract: A method for fluorophore bias removal in microarray experiments in which the fluorophores used in microarray experiment pairs are reversed. Further, a method for calculating the individual errors associated with each measurement made in nominally repeated microarray experiments. This error measurement is optionally coupled with rank based methods in order to determine a probability that a cellular constituent is up or down regulated in response to a perturbation. Finally, a method for determining the confidence in the weighted average of the expression level of a cellular constituent in nominally repeated microarray experiments.

Abstract: Methods are disclosed for the identification of gene sets that are differentially expressed in PBMCs of patients diagnosed with a pre-diabetic disease state and overt type II diabetes. 3 gene and 10 gene signatures are shown to accurately predict a diabetic disease state in a patient. The application also described kits for the rapid diagnosis of diabetic disease states in patients at a point of care facility.

Abstract: Embodiments disclosed herein relate to methods and systems for performing an automated assay, and particularly to performing an assay on a plurality of samples on an automated instrument.

Abstract: An analytic apparatus and method is provided for diagnosis, prognosis and biomarker discovery using transcriptome data such as mRNA expression levels from microarrays, proteomic data, and metabolomic data. The invention provides for model-based analysis, especially using kernel-based models, and more particularly similarity-based models. Model-derived residuals advantageously provide a unique new tool for insights into disease mechanisms. Localization of models provides for improved model efficacy. The invention is capable of extracting useful information heretofore unavailable by other methods, relating to dynamics in cellular gene regulation, regulatory networks, biological pathways and metabolism.

Abstract: A system and method for performing similarity searching is disclosed. This includes a programmable logic device configured to include a pipeline that comprises a matching stage, the matching stage being configured to receive a data stream comprising a plurality of possible matches between a plurality of data strings and a plurality of substrings of a query string. The pipeline may further include an ungapped extension prefilter stage located downstream from the matching stage, the prefilter stage being configured to shift through pattern matches between the data strings and the plurality of substrings of a query string and provide a score so that only pattern matches that exceed a user defined score will pass downstream from the prefilter stage. The matching stage may include at least one Bloom filter.

Abstract: The present disclosure relates generally to the field of epigenetics and in particular epigenetic profiles associated with a pathological condition. The present specification teaches screening of individuals and populations for epigenetic profiles associated with a pathological condition. The epigenetic profiles can be from an intron, an intron/exon boundary or a splicing region. Epigenetic profiles are disclosed from the following sites in the FMR locus: FREES, intron 2 of FMR1, the genomic FREE2 region as a whole or specific FREE2 fragments including FREE2 (D) or FREE2 (E). Kits and diagnostic assays are also taught herein as are computer programs to monitor changes in epigenetic patterns and profiles. Further enabled herein is a method for screening for agents which can reduce or mask the adverse effects of epigenetic modification and the use of these agents in therapy and prophylaxis.

Abstract: The present invention involves an analysis method of cellular chromosomes, particularly involves a method of analyzing whether a difference exists in the chromosome number between amniotic cells and standard cells by a sequencing method.

Abstract: Aspects of the present invention include methods and compositions for determining the number of individual polynucleotide molecules originating from the same genomic region of the same original sample that have been sequenced in a particular sequence analysis configuration or process. In these aspects of the invention, a degenerate base region (DBR) is attached to the starting polynucleotide molecules that are subsequently sequenced (e.g., after certain process steps are performed, e.g., amplification and/or enrichment). The number of different DBR sequences present in a sequencing run can be used to determine/estimate the number of different starting polynucleotides that have been sequenced. DBRs can be used to enhance numerous different nucleic acid sequence analysis applications, including allowing higher confidence allele call determinations in genotyping applications.

Abstract: Summarizing an aggregate contribution to a characteristic for an individual is disclosed, including determining the characteristic to be evaluated, identifying one or more markers associated with the characteristic, retrieving the measurement of the individual for each of the one or more markers from a database of individuals' markers, retrieving a statistical factor that measures the association between the marker associated with the characteristic and the characteristic for each of the one or more markers from the marker database, and determining the aggregate contribution based at least in part on the retrieved statistical factors.

Abstract: The amino acid sequence is deduced by using de novo sequencing, to prevent the correct amino acid sequence from not being ranked high as candidates. Amino acid sequence candidates are computed by finding the longest path by a branch and using a bound method based on the spectrum data on the target peptide and the known amino acid sequence. A tree-structured directed graph is used where amino acid sequences are set as nodes and the peak intensities corresponding to the amino acids are set as branches. In a sequence put at a node in the highest layer, an amino acid is placed at a terminal, and as the layer goes deeper, amino acids are sequentially placed from both terminals toward the center of the sequence. The final score is estimated based on the remaining amino acids, and if the score is small, the search is halted.

Abstract: A method of enhancing the throughput and applicability of NMR-based structure determination of protein-ligand complexes is disclosed. The method circumvents the need for protein sequence-specific resonance assignments and combines NMR data analysis and ligand docking methods into an integrated process. In one embodiment, NMR data is used to filter docking results to identify the most consistent binding modes, thereby providing structural information in a high-throughput fashion without the need for assigning protein resonances. Trial assignments for protein-ligand nuclear Overhauser effect (NOE) interactions are also produced by the method.

Abstract: Methods for genotyping polymorphisms using allele specific probes are disclosed. A training set is used to generate a model for each polymorphism to be interrogated. The training set is used to obtain an estimate of the asymmetry between an intensity measurement for a first allele and an intensity measurement for a second allele of the same polymorphism. The intensity measurement obtained for a test sample is adjusted using the estimate of asymmetry prior to using the intensity measurements to make a genotyping call. In preferred embodiments the adjustment is applied to polymorphisms that have a likelihood of being heterozygous that is above a specified threshold.

Abstract: Methods and apparatuses for nucleic aced sequencing using a compacted code technique are disclosed. In one embodiment, a method includes providing a nucleic acid to be sequenced, determining the identity of each base in a subsequence of bases in the nucleic acid, encoding the identity of the subsequence in a format having a number of bytes that is less than the number of bases, and storing the encoded identity.

Abstract: Methods, systems, and compositions can determine gene expression level of a specified cell-type subpopulation by direct analysis of a cell mixture sample composed of multiple subpopulations of various cell-types without the need of prior separation of the component cell-type subpopulations. A target gene and a reference gene can be identified as being informative for a specific cell-type subpopulation when at least 50% of the gene's transcripts in the cell mixture are from the subpopulation. This relative expression level in the cell mixture of the informative target and reference genes can correlate to the relative expression when measured in the isolated subpopulation. Thus, a similar biomarker can be obtained without the difficult step of isolating the cells of the subpopulation.

Abstract: Provided herein are methods of determining a subject's need for an implanted cardiac defibrillator, methods of determining a subject's risk for sudden cardiac death (SCD), arrhythmias, or heart failure, methods of determining a subject's need for an anti-arrhythmic agent, e.g., a sodium channel blocker, and methods of reducing risk of SCD in a subject. In exemplary embodiments, each of the methods comprise the step of determining a ratio, RS, which compares a level of a truncated SCN5A Exon 28 transcript of a biological sample obtained from the subject to (i) a level of a full length SCN5A Exon 28 transcript of the biological sample or (ii) a level of all SCN5A Exon 28 transcripts of the biological sample or (iii) a level of a full length SCN5A Exon 28 transcript and a level or one or more truncated SCN5A Exon 28 transcripts.

Abstract: A method for constructing a consensus sequence from a sequence alignment. The consensus sequence may be used to generate molecular standards that may substitute for genomic DNA in various assays. Since a molecular standard cannot have unresolved bases, the method removes less informative sequences to resolve all positions in the alignment. Also includes several sequences from pathogenic waterborne species that were constructed according to the method.

Abstract: A method for determining whether a nucleotide sequence contains a microRNA binding site and which microRNA will bind thereto is provided. For example, in one aspect of the invention, a method for determining whether a nucleotide sequence contains a microRNA binding site and which microRNA sequence will bind thereto is comprised of the following steps. One or more patterns are generated by processing a collection of known mature microRNA sequences. The reverse complement of each generated patter is then computed. One or more attributes are then assigned to the reverse complement of the one or more generated patterns. The one or more patterns that correspond to a reverse complement having one or more assigned attributes that satisfy at least one criterion are thereafter subselected. Each subselected pattern is then used to analyze the nucleotide sequence, such that a determination is made whether the nucleotide sequence contains a microRNA binding site and which microRNA sequence will bind thereto.

Abstract: Method for identifying disease-related pathways that can used to identify discovery targets, to identify new uses for known drugs, to identify markers for drug response, and related purposes.

Abstract: A system and method for performing non-binary comparison of biological sequences includes a new measure ?0, which is a non-binary counting measure that is used in a stand alone module called VaSSA-1. This measure obtains substantially more information about sequences and comparisons between them than is gathered by conventional bioinformatics techniques.

Abstract: Methods and systems for high-confidence utilization of datasets are disclosed. In one embodiment, the method includes selecting a metric for determining substantially optimal combination of true positives and false positives in a data set, applying an optimization technique, and obtaining, from the results of the optimization technique, a value for at least one optimization parameter, the value for at least one optimization parameter resulting in substantially optimal combination of true positives and false positives. A number of true positives and a number of false positives are a function of the one or more optimization parameters.

Abstract: Multiplex barcoded Paired-End Ditag (mbPED) library construction for ultra high throughput sequencing is disclosed. The mbPED library comprises multiple types of barcoded Paired-End Ditag (bPED) nucleic acid fragment constructs, each of which comprises a unique barcoded adaptor, a first tag, and a second tag linked to the first tag via the barcoded adaptor. The two tags are the 5?- and 3?-ends of a nucleic acid molecule from which they originate. The barcoded adaptor comprises a barcode, a first polynucleotide sequence comprising a first restriction enzyme (RE) recognition site, and a second polynucleotide sequence comprising a second RE recognition site and covalently linked to the first polynucleotide sequence via the barcode. The two REs lead to cleavage of a nucleic acid at a defined distance from their recognition sites. The length of the adaptor is set so that the bPED nucleic acid fragment fits one-step sequencing.

Abstract: The disclosed subject matter is directed to genetic linkage methods for identifying genetic determinants of transcription factor activity. An inferred transcription factor activity profile is generated based on a nucleotide sequence-specific mathematical model of gene expression regulation. Genetic linkage analysis is performed to identify at least one genetic determinant linked to a specific transcription factor segregant based on the inferred transcription factor profile.

Abstract: The present invention relates to methods and systems for the analysis of the dissociation behavior of nucleic acids. The present invention includes methods and systems for analyzing dynamic profiles of genotypes of nucleic acids, including the steps of using a computer, including a processor and a memory, to convert dynamic profiles of known genotypes of a nucleic acid to multi-dimensional data points, wherein the dynamic profiles each comprise measurements of a signal representing a physical change of a nucleic acid containing the known genotype relative to an independent variable; using the computer to reduce the multi-dimensional data points into reduced-dimensional data points; and generating a plot of the reduced-dimensional data points for each genotype.

Abstract: This document provides materials and methods involved in nucleic acid sequence analysis. For example, methods and materials for distinguishing sequencing errors (e.g., sequencing and/or PCR artifacts) from true polymorphic sequence variations (e.g., single-nucleotide polymorphisms, sequence insertions, sequence deletions, or combinations thereof) are provided. In addition, methods and materials for determining homozygosity or heterozygosity are provided.

Abstract: A two-tiered classification system that can be integrated with the current algorithm used by pathologists for identification of the site of origin for ‘malignancy with unknown primary ’ is presented. In use, morphology, immunohistochemical (IHC) studies, and microarry-based top tier gene expression classifiers first subclassify cytokeratin positive carcinomas into adenocarcinoma, squamous cell carcinoma, neuroendocrine carcinoma and urothelial carcinoma. Subsequently, organ-specific IHC-markers, if available, are used in conjunction with microarray-based second tier gene expression classifiers to assign the primary site of origin to the sample. This new hybrid approach combines IHC with a hierarchy of quantitative gene expression based classifiers into an algorithmic method that can assist pathologists to further refine and support their decision making process.

Abstract: According to embodiments, techniques for extracting a signal parameter from a selected region of a generally repetitive signal are disclosed. A pulse oximetry system including a sensor or probe may be used to obtain an original photoplethysmograph (PPG) signal from a subject. A filter transformation may be applied to the original PPG signal to produce a baseline PPG signal. The baseline PPG signal may contain artifacts and/or noise, and a region of the baseline PPG signal suitable for extracting the signal parameter may be selected. A suitable region of the baseline PPG signal may be selected by applying one or more thresholds to the baseline PPG signal, where the values of the thresholds may be set based on derivative values, amplitude-based percentiles, and/or local minima and maxima of the baseline PPG signal. A portion of the original PPG signal corresponding to the selected region may be processed, and the signal parameter may be extracted from the processed region.

Abstract: Described herein is a method for identifying an aberrant feature on a nucleic acid array. In general terms, the method comprises: a) obtaining a log transformed normalized value indicating the amount of hybridization of a test sample to a first feature on the nucleic acid array; b) calculating a z-score for the first feature using: the log transformed normalized value; and the distribution of reference log transformed normalized values that indicate the amount of hybridization of control samples to the same feature on a plurality of reference arrays; and c) identifying the test feature as aberrant if it has a z-score that is above or below a defined threshold.

Abstract: The present invention relates to systems and methods capable of characterizing populations of organisms within a sample. The characterization may utilize probabilistic matching of short strings of sequencing information to identify genomes from a reference genomic database to which the short strings belong. The characterization may include identification of the microbial community of the sample to the species and/or sub-species and/or strain level with their relative concentrations or abundance. In addition, the system and methods may enable rapid identification of organisms including both pathogens and commensals in clinical samples, and the identification may be achieved by a comparison of many (e.g., hundreds to millions) metagenomic fragments, which have been captured from a sample and sequenced, to many (e.g., millions or billions) of archived sequence information of genomes (i.e., reference genomic databases).

Abstract: Described herein are systems and processes for designing the sequence of one or more interacting nucleic acid strands intended to adopt a target secondary structure at equilibrium. The target secondary structure is decomposed into a binary tree and candidate mutations are evaluated on leaf nodes of the tree. During a process of leaf optimization, defect-weighted mutation sampling is used to select each candidate mutation position with a probability proportional to its contribution to an ensemble defect of the leaf. Subsequences of the tree are then merged, moving up the tree until a final nucleotide sequence of interest is determined that has the target secondary structure at equilibrium.

Abstract: A method and system are provided for evaluating the correlation between sequences by entering segments of one sequence in a database and comparing segments of the other sequence with the index values to find correlated segments. The correlated segments are analysed to determine whether the spacing is within a defined range indicating that a correlation threshold has been met. A processing methodology may be employed whereby a coarse potential alignment algorithm is first applied to determine potential alignment at a plurality of potential alignment positions, which are filtered based on alignment scores, and a fine alignment algorithm is then applied.

Abstract: The present invention relates to a method, system and software arrangement for determining the co-associations of allele types across consecutive loci and hence for reconstructing two haplotypes of a diploid individual from genotype data generated by mapping experiments with single molecules, families or populations. The haplotype reconstruction system, method and software arrangement of the present invention can utilize a procedure that is nearly linear in the number of polymorphic markers examined, and is therefore quicker, more accurate, and more efficient than other population-based approaches. The system, method, and software arrangement of the present invention may be useful to assist with the diagnosis and treatment of any disease, which has a genetic component.