METHODS AND SYSTEMS FOR MODELING PHASING EFFECTS IN SEQUENCING USING TERMINATION CHEMISTRY

摘要

A method for nucleic acid sequencing includes receiving observed or measured nucleic acid sequencing data from a sequencing instrument that receives and processes a sample nucleic acid in a termination sequencing-by-synthesis process. The method also includes generating a set of candidate sequences of bases for the observed or measured nucleic acid sequencing data by determining a predicted signal for candidate sequences using a simulation framework. The simulation framework incorporates an estimated carry forward rate (CFR), an estimated incomplete extension rate (IER), an estimated droop rate (DR), an estimated reactivated molecules rate (RMR), and an estimated termination failure rate (TFR), the RMR being greater than or equal to zero and the TFR being lesser than one. The method also includes identifying, from the set of candidate sequences of bases, one candidate sequence leading to optimization of a solver function as corresponding to the sequence for the sample nucleic acid.

主权项

1. A method for nucleic acid sequencing, comprising:
receiving observed or measured nucleic acid sequencing data from a sequencing instrument configured to receive a sample nucleic acid and to process the sample nucleic acid in a termination sequencing-by-synthesis process; generating a set of candidate sequences of bases for the observed or measured nucleic acid sequencing data by determining a predicted signal for candidate sequences using a simulation framework for simulating possible state transitions for active and inactive molecules present at a K-th base during an N-th nucleotide flow, where K and N denote indices associated with bases and nucleotide flows, respectively, wherein the simulation framework for simulating the possible state transitions incorporates an estimated carry forward rate (CFR), an estimated incomplete extension rate (IER), an estimated droop rate (DR), an estimated reactivated molecules rate (RMR), and an estimated termination failure rate (TFR), the RMR being greater than or equal to zero and the TFR being lesser than one; and identifying, from the set of candidate sequences of bases, one candidate sequence leading to optimization of a solver function as corresponding to the sequence for the sample nucleic acid.