System and method to correct out of phase errors in DNA sequencing data by use of a recursive algorithm
First Claim
1. A method for recursively correcting an error associated with phasic synchrony of nucleic acid sequence data generated from a population of substantially identical copies of a template molecule, comprising:
- (a) detecting a plurality of signals generated in response to a plurality of nucleotide species introduced during a sequencing reaction;
(b) generating an observed value for the signal detected from each of the nucleotide species;
(c) defining a plurality of positive incorporation values and a plurality of negative incorporation values from the observed values using a carry forward value and an incomplete extension value;
(d) simultaneously calculating a carry forward perturbation increment and an incomplete extension perturbation increment;
(e) revising the carry forward value and the incomplete extension value using the carry forward perturbation increment and the incomplete extension perturbation increment;
(f) re-defining the plurality of positive incorporation values and the plurality of negative incorporation values using the revised carry forward value and the revised incomplete extension value; and
(g) repeating steps (d)-(f) until convergence of the plurality of positive incorporation values and the plurality of negative incorporation values, thereby generating a corrected nucleic acid sequence read.
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Abstract
Provided herein are methods for correcting an error associated with phasic synchrony of sequence data generated from a population of template molecules by detecting signals generated in response to nucleotide species introduced during a sequencing reaction; generating an observed value for the signal detected from each of the nucleotide species; defining positive incorporation values and negative incorporation values from the observed values using a carry forward value and an incomplete extension value; revising the carry forward value and the incomplete extension value using a noise value derived from observed values associated with the negative incorporation values; re-defining the positive incorporation values and the negative incorporation values using the revised carry forward value and the revised incomplete extension value; and repeating the steps of revising and re-defining until convergence of the positive incorporation values and the negative incorporation values.
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Citations
17 Claims
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1. A method for recursively correcting an error associated with phasic synchrony of nucleic acid sequence data generated from a population of substantially identical copies of a template molecule, comprising:
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(a) detecting a plurality of signals generated in response to a plurality of nucleotide species introduced during a sequencing reaction; (b) generating an observed value for the signal detected from each of the nucleotide species; (c) defining a plurality of positive incorporation values and a plurality of negative incorporation values from the observed values using a carry forward value and an incomplete extension value; (d) simultaneously calculating a carry forward perturbation increment and an incomplete extension perturbation increment; (e) revising the carry forward value and the incomplete extension value using the carry forward perturbation increment and the incomplete extension perturbation increment; (f) re-defining the plurality of positive incorporation values and the plurality of negative incorporation values using the revised carry forward value and the revised incomplete extension value; and (g) repeating steps (d)-(f) until convergence of the plurality of positive incorporation values and the plurality of negative incorporation values, thereby generating a corrected nucleic acid sequence read. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
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9. A method for recursively correcting an error associated with phasic synchrony of nucleic acid sequence data generated from a population of substantially identical copies of a template molecule, comprising the steps of:
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(a) detecting a plurality of signals generated in response to a plurality of nucleotide species introduced during a sequencing reaction; (b) generating an observed value for the signal detected from each of the nucleotide species; (c) defining a plurality of positive incorporation values and a plurality of negative incorporation values from the observed values using a carry forward value and an incomplete extension value; (d) simultaneously calculating a carry forward perturbation increment and an incomplete extension perturbation increment; (e) revising the carry forward value and the incomplete extension value using the carry forward perturbation increment and the incomplete extension perturbation increment; (f) re-defining the plurality of positive incorporation values and the plurality of negative incorporation values using the revised carry forward value and the revised incomplete extension value; and (g) repeating steps (d)-(f) until convergence of the carry forward value and the incomplete extension value, thereby generating a corrected nucleic acid sequence read.
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10. A system for recursively correcting an error associated with phasic synchrony of nucleic acid sequence data generated from a population of substantially identical copies of a template molecule, comprising:
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(a) a sequencing instrument that detects a plurality of signals generated in response to a plurality of nucleotide species introduced during a sequencing reaction; (b) a computer comprising executable code stored thereon which performs a method comprising the steps of; i. generating an observed value for the signal detected from each of the nucleotide species; ii. defining a plurality of positive incorporation values and a plurality of negative incorporation values from the observed values using a carry forward value and an incomplete extension value; iii. simultaneously calculating a carry forward perturbation increment and an incomplete extension perturbation increment; iv. revising the carry forward value and the incomplete extension value using the carry forward perturbation increment and the incomplete extension perturbation increment; v. re-defining the plurality of positive incorporation values and the plurality of negative incorporation values using the revised carry forward value and the revised incomplete extension value; and vi. repeating steps iii-v until convergence of the carry forward value and the incomplete extension value, thereby generating a corrected nucleic acid sequence read. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17)
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Specification