Abstract: The invention provides methods and systems for reconstructing feature intensities from pixel level data. In certain embodiments, the invention uses an empirically determined transfer function to construct a theoretical estimate of pixel level data and then iteratively updates feature intensities based on a minimum multiplicative error between the pixel level data and the theoretical estimate of the pixel level data.

Abstract: The invention provides methods and systems for reconstructing feature intensities from pixel level data. In certain embodiments, the invention uses an empirically determined transfer function to construct a theoretical estimate of pixel level data and then iteratively updates feature intensities based on a minimum multiplicative error between the pixel level data and the theoretical estimate of the pixel level data.

Abstract: A method for sequencing a polynucleotide sample having a barcode sequence includes: introducing a series of nucleotides to the polynucleotide sample according to a predetermined order of nucleotide flows; obtaining a series of signals resulting from the introducing of nucleotides to the polynucleotide sample; and resolving the series of signals over the barcode sequence to render a flowspace string, wherein the flowspace string is a codeword of an error-correcting code that is (i) designed based on and adapted for use with the predetermined order of nucleotide flows, and (ii) capable of distinguishing any codeword in the error-correcting code from the other codewords in the error-correcting code in the presence of zero, one, and two errors.

Abstract: The invention provides methods and systems for reconstructing feature intensities from pixel level data. In certain embodiments, the invention uses an empirically determined transfer function to construct a theoretical estimate of pixel level data and then iteratively updates feature intensities based on a minimum multiplicative error between the pixel level data and the theoretical estimate of the pixel level data.

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

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

Abstract: Systems and method for determining variants can receive mapped reads and determine a distribution of matched-filter residuals distribution from a plurality of reads at a homopolymer region. The distribution of matched-filter residuals can be fit to uni-modal and bi-modal models. Based on the model that best fits the distribution of matched-filter residuals, the heterozygosity of the sample and the absence or presence of an insertion/deletion in the homopolymer can be determined.

Abstract: The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Abstract: A method for nucleic acid sequencing includes: disposing a plurality of template polynucleotide strands, sequencing primers, and polymerases in a plurality of defined spaces of a sensor array; exposing template polynucleotide strands to a series of flows of nucleotide species, the series comprising a sequence of random flows; and obtaining, for each of the series of flows of nucleotide species, a signal indicative of how many nucleotide incorporations occurred for that particular flow to determine a predicted sequence of nucleotides corresponding to the template polynucleotide strands.

Abstract: A compression method includes measuring a waveform associated with a chemical event occurring on a sensor array, wherein the waveform comprises at least one region associated with expected measured values and at least one region associated with unpredictable measured values; applying a first compression process to the waveform, the first compression process including an averaging of one or more frames in one or more portions of the waveform; and applying a second compression process to the waveform, the second compression process including a truncating of data corresponding to a portion of the waveform that is not related to a nucleotide incorporation component of the waveform.

Abstract: The invention provides arrays of immobilized probes, and methods employing the arrays, for detecting mutations in the biotransformation genes, such as cytochromes P450. For example, one such array comprises four probe sets. A first probe set comprises a plurality of probes, each probe comprising a segment of at least three nucleotides exactly complementary to a subsequence of a reference sequence from a biotransformation gene, the segment including at least one interrogation position complementary to a corresponding nucleotide in the reference sequence. Second, third and fourth probe sets each comprise a corresponding probe for each probe in the first probe set.

Abstract: A method for sequencing a polynucleotide sample having a barcode sequence, includes: introducing a series of nucleotides to the polynucleotide sample according to a predetermined flow ordering; obtaining a series of signals resulting from the introducing of nucleotides to the polynucleotide sample; and resolving the series of signals over the barcode sequence to render a flowspace string, wherein the flowspace string is a codeword of an error-tolerant code capable of distinguishing the barcode sequence from other barcode sequences in the presence of one or more errors.

Abstract: The invention provides methods and systems for reconstructing feature intensities from pixel level data. In certain embodiments, the invention uses an empirically determined transfer function to construct a theoretical estimate of pixel level data and then iteratively updates feature intensities based on a minimum multiplicative error between the pixel level data and the theoretical estimate of the pixel level data.

Abstract: The invention provides arrays of immobilized probes, and methods employing the arrays, for detecting mutations in the CFTR gene.

Abstract: The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Abstract: A method for nucleic acid sequencing includes disposing template polynucleotide strands in defined spaces on a sensor array, at least some of the template polynucleotide strands having a sequencing primer and a polymerase operably bound therewith; exposing the template polynucleotide strands to a series of flows of nucleotide species flowed according to a predetermined ordering; and determining, for each of the series of flows of nucleotide species, how many nucleotide incorporations occurred for that particular flow to determine a predicted sequence of nucleotides corresponding to the template polynucleotide strands, wherein the predetermined ordering (a) is not a series of consecutive repetitions of a 4-flow permutation of four different nucleotide species, (b) is not specifically tailored to a particular combination of a particular template polynucleotide strand to be sequenced and a particular sequencing primer to be used, and (c) comprises a phase-protecting flow ordering.

Abstract: An embodiment of a method of analyzing data from processed images of biological probe arrays is described that comprises receiving a plurality of files comprising a plurality of intensity values associated with a probe on a biological probe array; normalizing the intensity values in each of the data files; determining an initial assignment for a plurality of genotypes using one or more of the intensity values from each file for each assignment; estimating a distribution of cluster centers using the plurality of initial assignments; combining the normalized intensity values with the cluster centers to determine a posterior estimate for each cluster center; and assigning a plurality of genotype calls using a distance of the one or more intensity values from the posterior estimate.

Abstract: Methods for analyzing signal data generated by sequencing of a polynucleotide strand using a pH-based method of detecting nucleotide incorporation(s). In an embodiment, the method comprises formulating a function that models the output signal of a representative empty well of a reactor array. A time transformation is applied to the empty well function to obtain a time-warped empty well function. The time-warped empty well function is fitted to an output signal from the loaded well representative of a flow that results in a non-incorporation event in the loaded well. The fitted time-warped empty well function can then be used to analyze output signals from the loaded well for other flows.

Abstract: An embodiment of a method of analyzing data from processed images of biological probe arrays is described that comprises receiving a plurality of files comprising a plurality of intensity values associated with a probe on a biological probe array; normalizing the intensity values in each of the data files; determining an initial assignment for a plurality of genotypes using one or more of the intensity values from each file for each assignment; estimating a distribution of cluster centers using the plurality of initial assignments; combining the normalized intensity values with the cluster centers to determine a posterior estimate for each cluster center; and assigning a plurality of genotype calls using a distance of the one or more intensity values from the posterior estimate.

Abstract: The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.