Models for analyzing data from sequencing-by-synthesis operations
First Claim
1. A method of modeling a background signal when sequencing a polynucleotide strand using sequencing-by-synthesis, comprising:
- flowing a series of nucleotide flows onto a reactor array having multiple reaction confinement regions, one or more copies of the polynucleotide strand being located in a loaded reaction confinement region of the reactor array, the loaded reaction confinement region being located in a vicinity of one or more neighboring reaction confinement regions;
receiving output signals from the reactor array, the output signals being generated by the reactor array during the flowing of the series of nucleotide flows in response to chemical changes occurring in at least some of the reaction confinement regions;
estimating a background signal component of the received output signals for the loaded reaction confinement region using at least the received output signals and a background model representing at least an exchange of ions between the one or more neighboring reaction confinement regions and a headspace, the headspace being located adjacent to and above the loaded reaction confinement region and the one or more neighboring reaction confinement regions such that a bulk fluid, the loaded confinement region, and the one or more neighboring reaction confinement regions are modeled to exchange ions with each other through the headspace, wherein the background model is derived using a first characteristic equation that comprises a term related to a difference between a proton concentration in the loaded reaction confinement region and a proton concentration in the headspace; and
fitting an output signal model based on at least the estimated background signal component to the signal data, wherein the fitting is used to generate sequence data representative of nucleotide incorporations into the copies of the polynucleotide strands resulting from the series of nucleotide flows.
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Abstract
A method of modeling a background signal when sequencing a polynucleotide strand using sequencing-by-synthesis includes: flowing a series of nucleotide flows onto a reactor array having multiple reaction confinement regions, one or more copies of the polynucleotide strand being located in a loaded reaction confinement region of the reactor array, the loaded reaction confinement region being located in a vicinity of one or more neighboring reaction confinement regions that may or may not be loaded; receiving output signals from the reactor array; and modeling a background signal for the loaded reaction confinement region using the received output signals and a model adapted to account at least for an exchange of ions between the one or more neighboring reaction confinement regions and a headspace adjacent the loaded reaction confinement region and the one or more neighboring reaction confinement regions.
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Citations
19 Claims
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1. A method of modeling a background signal when sequencing a polynucleotide strand using sequencing-by-synthesis, comprising:
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flowing a series of nucleotide flows onto a reactor array having multiple reaction confinement regions, one or more copies of the polynucleotide strand being located in a loaded reaction confinement region of the reactor array, the loaded reaction confinement region being located in a vicinity of one or more neighboring reaction confinement regions; receiving output signals from the reactor array, the output signals being generated by the reactor array during the flowing of the series of nucleotide flows in response to chemical changes occurring in at least some of the reaction confinement regions; estimating a background signal component of the received output signals for the loaded reaction confinement region using at least the received output signals and a background model representing at least an exchange of ions between the one or more neighboring reaction confinement regions and a headspace, the headspace being located adjacent to and above the loaded reaction confinement region and the one or more neighboring reaction confinement regions such that a bulk fluid, the loaded confinement region, and the one or more neighboring reaction confinement regions are modeled to exchange ions with each other through the headspace, wherein the background model is derived using a first characteristic equation that comprises a term related to a difference between a proton concentration in the loaded reaction confinement region and a proton concentration in the headspace; and fitting an output signal model based on at least the estimated background signal component to the signal data, wherein the fitting is used to generate sequence data representative of nucleotide incorporations into the copies of the polynucleotide strands resulting from the series of nucleotide flows. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
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17. A non-transitory machine-readable storage medium comprising instructions which, when executed by a processor, cause the processor to:
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receive output signals generated in response to a flow of a series of nucleotides onto a reactor array having multiple reaction confinement regions, one or more copies of the polynucleotide strand being located in a loaded reaction confinement region of the reactor array, the loaded reaction confinement region being located in a vicinity of one or more neighboring reaction confinement regions, wherein the output signals are generated by the reactor array during the flowing of the series of nucleotide flows in response to chemical changes occurring in at least some of the reaction confinement regions; estimate a background signal component of the received output signals for the loaded reaction confinement region using at least the received output signals and a background model representing at least an exchange of ions between the one or more neighboring reaction confinement regions and a headspace, the headspace being located adjacent to and above the loaded reaction confinement region and the one or more neighboring reaction confinement regions such that a bulk fluid, the loaded confinement region, and the one or more neighboring reaction confinement regions are modeled to exchange ions with each other through the headspace, wherein the background model is derived using a first characteristic equation that comprises a term related to a difference between a proton concentration in each of the neighboring reaction confinement regions and a proton concentration in the headspace; and fit an output signal model to the based on at least the modeled background signal to the signal data, wherein the fitting is used to generate sequence data representative of nucleotide incorporations into the copies of the polynucleotide strands resulting from the series of nucleotide flows. - View Dependent Claims (18)
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19. A method of modeling a background signal when sequencing a polynucleotide strand using sequencing-by-synthesis, comprising:
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flowing a series of nucleotide flows onto a reactor array having multiple reaction confinement regions, one or more copies of the polynucleotide strand being located in a loaded reaction confinement region of the reactor array, the loaded reaction confinement region being located in a vicinity of one or more neighboring reaction confinement regions; receiving output signals from the reactor array, the output signals being generated by the reactor array during the flowing of the series of nucleotide flows in response to chemical changes occurring in at least some of the reaction confinement regions; estimating a background signal component of the received output signals for the loaded reaction confinement region using at least the received output signals and a background model representing at least an exchange of ions between the one or more neighboring reaction confinement regions and a headspace, the headspace being located adjacent to and above the loaded reaction confinement region and the one or more neighboring reaction confinement regions such that a bulk fluid, the loaded confinement region, and the one or more neighboring reaction confinement regions are modeled to exchange ions with each other through the headspace, wherein the background model is derived using a first characteristic equation that comprises a term related to a difference between a proton concentration in the loaded reaction confinement region and a proton concentration in the headspace; and fitting an output signal model based on at least the estimated background signal component to the signal data, wherein the fitting is used to generate sequence data representative of nucleotide incorporations into the copies of the polynucleotide strands resulting from the series of nucleotide flows.
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Specification