Abstract: Methods for substantially improved detection and analysis in nucleic acid hybridization assays are described. The methods provide the reliable estimation of background signal which derives primarily from nonspecific hybridization. The invention is useful in chemical, biological, medical and diagnostic techniques, as well as for drug discovery.

Abstract: Methods for correcting systematic errors in the measured position of deposited features of a nucleic acid array on a substrate. Systematic errors are modeled by an algorithmic model based on measuring the positions (and possibly other properties) of a subset of the features, and a model is constructed for predicting deviations in feature position from an ideal grid. Deviations arising in the deposition process, the scanning process, or both may be corrected.

Abstract: A method and system for extracting data signals from a scanned image resulting from optical, radiometric, or other types of analysis of a molecular array. The positions of corner features are first located. Then, an initial feature coordinate grid is determined from the positions of the corner features. A refined feature coordinate grid is then calculated based on the positions of strong features, and is used to identify the positions of weak features and the positions of the local background regions surrounding all features. Finally, signal intensity values are extracted from the features and their respective local background regions in the scanned image, and background-subtracted signal intensity values, background-subtracted and normalized signal intensity ratios, and variability information and confidence intervals are determined based on the extracted values.

Abstract: A method and system for employing pixel-based, signal-intensity data contained within areas of a scanned image of a molecular array corresponding to features and feature backgrounds in order to determine whether or not the features or feature backgrounds have non-uniform signal intensities and are thus outlier features and outlier feature backgrounds. A calculated, estimated variance for the signal intensities within a feature or feature background is compared to a maximum allowable variance calculated for the feature or feature background based on a signal intensity variance model. When the experimental variance is less than or equal to the maximum allowable variance, the feature or feature background is considered to have acceptable signal-intensity uniformity. Otherwise, the feature or feature background is flagged as an outlier feature or outlier feature background.

Abstract: A method for evaluating an orientation of a molecular array having features arranged in a pattern. An image of the molecular array is obtained by scanning the molecular array to determine data signals emanating from discrete positions on a surface of the molecular array. An actual result of a function on pixels of the image which pixels lie in a second pattern, is calculated. This actual result is compared with an expected result which would be obtained if the second pattern had a predetermined orientation on the array. Array orientation can then be evaluated based on the result.

Abstract: Systems and methods for displaying gene- and/or protein-related data with respect to chromosome maps at locations identifying relevant positioning of the genes with which the gene- and/or protein related data are associated. Multiple experiments may be plotted onto the display adjacent one or more chromosome maps. Automatic extraction of genomic location, based on accession numbers or other unique identifiers and cross connection with expression data is provided. Statistical assessments of correlations between expression and genome localization may be performed. Zooming capabilities, thumbnail/fullview toggling, browsability and linked data may be included as features of the visualization systems described.

Abstract: A method and system for determining the sequence of nucleic-acid polymers that is particularly useful for identifying various combinations of subsequences of a longer nucleic-acid sequence. Positive probes, including tiling probes, jump probes, and exonic tiling probes, are employed within a microarray, along with a number of different types of negative control probes, including deletion-negative-control probes, reverse-jump-negative-control probes, exon-linker-negative-control probes, and intron/exon-negative-control probes. The different types of positive probes combined with the different types of negative control probes provide a more precise and less ambiguous determination of various subsequent combinations that, for example, result from post-transcriptional splicing of mRNA transcripts.

Abstract: A method of processing one or more detected signal images each acquired from a field of view of a chemical array reader. A location correction is determined based on different detected signals at different image regions which represent regions in the field of view having the same actual signal. Alternatively or additionally, a location correction is applied to a detected signal at an image region. The location correction reduces detected signal discrepancy between different regions in an acquired image which represent different regions in the field of view having the same actual signal. An array reading system and computer program products are also provided.

Abstract: A method for evaluating an orientation of a molecular array having features arranged in a pattern. An image of the molecular array is obtained by scanning the molecular array to determine data signals emanating from discrete positions on a surface of the molecular array. An actual result of a function on pixels of the image which pixels lie in a second pattern, is calculated. This actual result is compared with an expected result which would be obtained if the second pattern had a predetermined orientation on the array. Array orientation can then be evaluated based on the result.

Abstract: Apparatus and methods are disclosed for imaging surfaces that comprise a sample. One embodiment of the present invention is an imaging apparatus comprising a holder for a surface, a light source adapted to illuminate the surface, a diffractive element between the holder and the light source and an imaging detector adapted to receive light from the surface. In a method for imaging a surface comprising a plurality of discrete features, light is selectively diffracted on to one or more predetermined features of the surface at a predetermined point in time. This step is repeated until substantially all of the features on the surface are illuminated. Light is detected from the surface to thereby image the surface.

Abstract: An extensible, generalized architecture, an application programming interface, software and methods for building data overlays, as well as software, a system, methods and interface for building specific data overlays, with particular relevance to biological data.

Abstract: Apparatus and methods are disclosed for imaging surfaces that comprise a sample. One embodiment of the present invention is an imaging apparatus comprising a holder for a surface, a light source adapted to illuminate the surface, a diffractive element between the holder and the light source and an imaging detector adapted to receive light from the surface. In a method for imaging a surface comprising a plurality of discrete features, light is selectively diffracted on to one or more predetermined features of the surface at a predetermined point in time. This step is repeated until substantially all of the features on the surface are illuminated. Light is detected from the surface to thereby image the surface.

Abstract: A method and system for normalizing two or more molecular array data sets. Input molecular array data sets are separately globally normalized by, for example, dividing the feature-signal magnitudes of each data set by the geometric mean of the feature-signal magnitudes of the data set. The globally normalized feature signal magnitudes within each data set are ranked in ascending order. A numeric function is created that relates feature-signal magnitudes of the data sets. Only a subset of the features, obtained by selecting features that are similarly ranked in the separate feature-signal-magnitude rankings for the data sets, is used to construct the numeric function. The numeric function is smoothed by one of many possible different smoothing procedures.

Abstract: A method and system for normalizing two or more molecular array data sets. Input molecular array data sets are separately globally normalized by, for example, dividing the feature-signal magnitudes of each data set by the geometric mean of the feature-signal magnitudes of the data set. The globally normalized feature signal magnitudes within each data set are ranked in ascending order. A numeric function is created that relates feature-signal magnitudes of the data sets. Only a subset of the features, obtained by selecting features that are similarly ranked in the separate feature-signal-magnitude rankings for the data sets, is used to construct the numeric function. The numeric function is smoothed by one of many possible different smoothing procedures.

Abstract: A method and system for visual display of feature extraction results to a user of a molecular array feature extraction software package. The feature extraction results are displayed as visual marks superimposed on an image of a molecular array, and numerical and textual feature extraction results for, and other information about, a particular feature may be displayed to a user when the user positions a mouse cursor over the feature in the displayed image. A user may direct display of visual mark for only statistically invalid features and feature backgrounds.

Abstract: A method and system for extracting data signals from a scanned image resulting from optical, radiometric, or other types of analysis of a molecular array. The positions of corner features are first located. Then, an initial feature coordinate grid is determined from the positions of the corner features. A refined feature coordinate grid is then calculated based on the positions of strong features, and is used to identify the positions of weak features and the positions of the local background regions surrounding all features. Finally, signal intensity values are extracted from the features and their respective local background regions in the scanned image, and background-subtracted signal intensity values, background-subtracted and normalized signal intensity ratios, and variability information and confidence intervals are determined based on the extracted values.

Abstract: A method and system for employing pixel-based, signal-intensity data contained within areas of a scanned image of a molecular array corresponding to features and feature backgrounds in order to determine whether or not the features or feature backgrounds have non-uniform signal intensities and are thus outlier features and outlier feature backgrounds. A calculated, estimated variance for the signal intensities within a feature or feature background is compared to a maximum allowable variance calculated for the feature or feature background based on a signal intensity variance model. When the experimental variance is less than or equal to the maximum allowable variance, the feature or feature background is considered to have acceptable signal-intensity uniformity. Otherwise, the feature or feature background is flagged as an outlier feature or outlier feature background.

Abstract: Methods for correcting systematic errors in the measured position of deposited features of a nucleic acid array on a substrate. Systematic errors are modeled by an algorithmic model based on measuring the positions (and possibly other properties) of a subset of the features, and a model is constructed for predicting deviations in feature position from an ideal grid. Deviations arising in the deposition process, the scanning process, or both may be corrected.

Abstract: A method and system for extracting data signals from a scanned image resulting from optical, radiometric, or other types of analysis of a molecular array. The positions of corner features are first located. Then, an initial feature coordinate grid is determined from the positions of the corner features. A refined feature coordinate grid is then calculated based on the positions of strong features, and is used to identify the positions of weak features and the positions of the local background regions surrounding all features. Finally, signal intensity values are extracted from the features and their respective local background regions in the scanned image, and background-subtracted signal intensity values, background-subtracted and normalized signal intensity ratios, and variability information and confidence intervals are determined based on the extracted values.

Abstract: Methods and reagents are disclosed which provide for more sensitive, more accurate and higher through-put analyses of target nucleic acid sequences. The methods and reagents of the present invention may be generically applied to generally any target nucleic acid sequence and do not require a priori information about the presence, location or identity of mutations in the target nucleic acid sequence. The reagents of the invention are mixtures of oligonucleotide precursors having a high level of coverage and mass number complexity, and also having tags analyzable by mass spectrometry which are covalently linked to the precursors through cleavable bonds. A method is also disclosed for analyzing a target nucleic acid sequence employing the mixtures of oligonucleotide precursors having tags analyzable by mass spectrometry covalently linked to the oligonucleotide precursors through cleavable bonds, and chemical or enzymatic assays to alter the mass of the oligonucleotide precursors prior to mass spectral analysis.