Abstract: The invention takes a unique approach to transcript analysis that provides a novel DGE technology based on single-molecule sequencing. More particularly, the invention relates to methods and compositions for analyzing and identifying genes and gene expression and transcript profiles using a DGE-based technology and single molecule sequencing that does not require amplification or fragmentation.

Abstract: Methods and systems for identifying and selecting nucleic acid probes for detecting a target with a nucleic acid probe array or comparative genome hybridization microarray, comprising selecting a plurality of potential target sequences, generating a plurality of candidate probes from the target sequences, filtering the plurality of candidate probes by analyzing candidate probes for selected probe properties in silico. Microarrays comprising probes selected by the methods of the invention are particularly useful for comparative genome hybridization and location analysis.

Abstract: The invention generally relates to methods for detecting fetal nucleic acids and methods for diagnosing fetal abnormalities. In certain embodiments, the invention provides methods for determining whether fetal nucleic acid is present in a maternal sample including obtaining a maternal sample suspected to include fetal nucleic acids, and performing a sequencing reaction on the sample to determine presence of at least a portion of a Y chromosome in the sample, thereby determining that fetal nucleic acid is present in the sample. In other embodiments, the invention provides methods for quantitative or qualitative analysis to detect fetal nucleic acid in a maternal sample, regardless of the ability to detect the Y chromosome, particularly for samples including normal nucleic acids from a female fetus.

Abstract: The invention generally relates to methods for detecting fetal nucleic acids and methods for diagnosing fetal abnormalities. In certain embodiments, the invention provides methods for determining whether fetal nucleic acid is present in a maternal sample including obtaining a maternal sample suspected to include fetal nucleic acids, and performing a sequencing reaction on the sample to determine presence of at least a portion of a Y chromosome in the sample, thereby determining that fetal nucleic acid is present in the sample. In other embodiments, the invention provides methods for quantitative or qualitative analysis to detect fetal nucleic acid in a maternal sample, regardless of the ability to detect the Y chromosome, particularly for samples including normal nucleic acids from a female fetus.

Abstract: Methods and kits for selective preparing cDNA relatively free of sequences found in rRNA and subcellular RNAs are disclosed. The methods and kits utilize approximately 200 hexamer sequences which target messenger RNA. The methods and kits are useful in preparing samples for sequencing analysis, especially when performing single molecule sequencing by synthesis.

Abstract: Methods for preparing fragments for nucleic acids sequence analysis that demonstrates uniform coverage across the full fragment length. The methods disclosed herein are useful for candidate gene re-sequencing wherein the detailed analysis is performed on selected, amplified regions of the genome.

Abstract: The invention generally provides methods for analyzing and constructing nucleic acid sequences and more specifically for assembling a collection of short read nucleic acid sequences to construct longer nucleic acid sequences.

Abstract: An SPR sensor comprising a thin conducting layer comprising at least one conductive element formed on a surface of a transparent substrate, a light source that illuminates an interface between the conducting layer and the substrate, a photosensitive surface that generates signals from light reflected from the interface, a flow cell formed with at least one flow channel having a lumen defined by a wall formed from an elastic material and from a region of the conducting layer, and at least one hollow fluid-providing flow control apparatus having a lumen and an orifice communicating with its lumen. Fluid flow is enabled between the flow channel and the lumen of the flow control apparatus by forcing an end of the flow control apparatus through the elastic material so that the orifice communicates with the flow channel lumen.

Abstract: An SPR sensor comprising: a thin conducting layer comprising at least one conductive element formed on a surface of a transparent substrate; an illumination system controllable to illuminate an interface between the conducting layer and the substrate; a photosensitive surface that generates signals responsive to light from the light source that is reflected from a region of the interface; a flow cell formed with at least one flow channel having a lumen defined by a wall at least a portion of which is formed from an elastic material and a portion of which is formed by a region of the conducting layer; and at least one hollow needle having an exit orifice communicating with the needle's lumen and wherein fluid flow is enabled between the flow channel and the needle's lumen by puncturing the elastic material with the at least one needle so that the exit orifice communicates with the flow channel lumen.

Abstract: An SPR sensor comprising: a thin conducting layer comprising at least one conductive element formed on a surface of a transparent substrate; an illumination system controllable to illuminate an interface between the conducting layer and the substrate; a photosensitive surface that generates signals responsive to light from the light source that is reflected from a region of the interface; a flow cell formed with at least one flow channel having a lumen defined by a wall at least a portion of which is formed from an elastic material and a portion of which is formed by a region of the conducting layer; and at least one hollow needle having an exit orifice communicating with the needle's lumen and wherein fluid flow is enabled between the flow channel and the needle's lumen by puncturing the elastic material with the at least one needle so that the exit orifice communicates with the flow channel lumen.

Abstract: An SPR sensor comprising: a thin conducting layer comprising at least one conductive element formed on a surface of a transparent substrate; an illumination system controllable to illuminate an interface between the conducting layer and the substrate; a photosensitive surface that generates signals responsive to light from the light source that is reflected from a region of the interface; a flow cell formed with at least one flow channel having a lumen defined by a wall at least a portion of which is formed from an elastic material and a portion of which is formed by a region of the conducting layer; and at least one hollow needle having an exit orifice communicating with the needle's lumen and wherein fluid flow is enabled between the flow channel and the needle's lumen by puncturing the elastic material with the at least one needle so that the exit orifice communicates with the flow channel lumen.

Abstract: A polymerase chain reaction (PCR) mixture containing at least one unstructured nucleic acid primer pair is provided. In certain embodiments, the mixture may also contain: nucleotides, a DNA polymerase, and PCR reaction reagents, as well as a nucleic acid sample. The reaction mixture may be employed in, for example, a PCR reaction.

Abstract: Methods for identification of statistically significant combinatorial patterns in CGH data that are indicative of the progression of chromosomal aberrations in tumors. The methods comprise acquiring comparative genomic hybridization data, identifying a long order preserving subset within the comparative genomic hybridization data, and identifying a chromosomal aberration associated with the long order preserving subset.

Abstract: Various embodiments of the present invention are directed to methods and systems for automatic, statistically meaningful detection of aberrations common to multiple samples within a sample set. Many various aberration-calling techniques are used to identify aberrant intervals within each of the samples of the sample set. A set of candidate intervals is constructed to include the aberrant intervals identified by the aberration-calling technique, as well as two-way intersections of the identified aberrant intervals. A score indicating the statistical relevance of each candidate interval with respect to each sample is next assigned to each candidate interval. Then, a total significance score is assigned to each candidate interval based on the individual scores for the candidate interval with respect to each sample. The most statistically significant candidate intervals may be selected based on the total significance scores assigned to the candidate intervals.

Abstract: Various embodiments of the present invention determine a zero point, or centralization constant ?, for an array-based comparative genomic hybridization (“aCGH”) data set by identifying a zero-point value, or centralization constant ?, that, when used in an aberration-calling analysis of the aCGH data, results in the fewest number of array-probe-complementary genomic sequences identified as having abnormal copy numbers with respect to a control genome, or, in other words, results in the greatest number of array-probe-complementary genomic sequences identified as having normal copy numbers. In one embodiment, interval-based analysis of an aCGH data set may be carried out using a range of putative zero-point values, and the zero-point value for which the maximum number of genomic sequences are determined to have normal copy numbers may then be selected.

Abstract: A method for determining one or more kinetic parameters of binding between a first binding member and a second binding member. The method comprises adsorbing the first binding member to a surface at a plurality of microspots. The second binding member is then presented to the first binding member at each of the microspots, there being a plurality of combinations of first binding member surface density and second binding member concentration among the plurality of microspots. Data indicative of a binding reaction between the first of microspots are then obtained and analyzed so as to obtain one or more kinetic parameters of the binding between the first and second binding members. The invention also provides a system for carrying out the method. A method for localizing a molecular species at microspots on a surface, and a probe array produced by the method are also provided.

Abstract: Embodiments of the present invention are directed to increasing the reliability, precision, and resolution of identification, by analysis of comparative genomic hybridization (“CGH”) data and array-based comparative genomic hybridization (“aCGH”) data, of intervals along one or more chromosomes in which the copy number of the DNA subsequence within the interval in a sample genome is difference from the copy number of the DNA subsequence within a standard, or normal, genome. In various embodiments of the present invention, statistical data-quality measures are incorporated into comprehensive, quality-based interval-scores.

Abstract: Methods, tools, systems and computer readable media for analyzing CGH data, together with data from an independent source. Independent data is compared with the CGH data, wherein the CGH data is characterized by sets of defined regions differentiated by at least one property. Enrichment is assessed for at least one subset of the data from an independent source with regard to at least one of the sets of defined regions in the CGH data. Methods, tools, systems and computer readable media for visualizing CGH data as it is impacted by data from an independent source are also provided. A relationship between at least one defined set of the CGH data and at least one set of sequence elements defined in the data from an independent source may be visualized.

Abstract: Methods and systems for identifying and selecting nucleic acid probes for detecting a target with a nucleic acid probe array or comparative genome hybridization microarray, comprising selecting a plurality of potential target sequences, generating a plurality of candidate probes from the target sequences, filtering the plurality of candidate probes by analyzing candidate probes for selected probe properties in silico. Microarrays comprising probes selected by the methods of the invention are particularly useful for comparative genome hybridization and location analysis.

Abstract: An SPR sensor comprising: a thin conducting layer comprising at least one conductive element formed on a surface of a transparent substrate; an illumination system controllable to illuminate an interface between the conducting layer and the substrate; a photosensitive surface that generates signals responsive to light from the light source that is reflected from a region of the interface; a flow cell formed with at least one flow channel having a lumen defined by a wall at least a portion of which is formed from an elastic material and a portion of which is formed by a region of the conducting layer; and at least one hollow needle having an exit orifice communicating with the needle's lumen and wherein fluid flow is enabled between the flow channel and the needle's lumen by puncturing the elastic material with the at least one needle so that the exit orifice communicates with the flow channel lumen.