System and method to correct out of phase errors in DNA sequencing data by use of a recursive algorithm

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:

• (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.

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:

• (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.