Method and system of estimating a sequence of polymer units

At least one non-transitory computer-readable storage medium having instructions encoded thereon that, when executed by at least one processor, cause the at least one processor to perform a method of estimating a sequence of polymer units in a polymer, the method comprising:

• controlling translocation of the polymer through a nanopore using an enzyme;
• detecting, using a measurement circuit coupled to electrodes arranged on each side of the nanopore, a sequence of measurements of the polymer, each measurement being indicative of an ion current flowing through the nanopore during said translocation of the polymer through the nanopore;
• using at least one processor, coupled to a memory, to perform:
• accessing, in the memory, a probabilistic model comprising, for a set of possible k-mers, wherein a k-mer is a group of k polymer units where k is a positive integer:
• transition weightings each representing a probability of transition from an origin k-mer to a destination k-mer immediately subsequent in a sequence representing the sequence of polymer units, and wherein, when k is greater than one, transitions to destination k-mers that have a sequence in which the first k-1 polymer units are the same as the last k-1 polymer units of associated origin k-mers have greater probabilities than other transitions;
• and
• emission weightings each representing a probability of obtaining given values of ion current measurements for a respective k-mer of the set of possible k-mers;
• determining likelihoods, for each ion current measurement in the detected sequence of measurements of the polymer, that the ion current measurement was produced by respective k-mers of the set of possible k-mers, by optimizing a sequence of states of the probabilistic model based on the detected sequence of ion current measurements, the transition weightings, and the emission weightings;
• and
• determining an estimated sequence of polymer units in the polymer based on the likelihoods determined for each ion current measurement.

A system comprising:

• at least one processor;
• and
• at least one non-transitory computer-readable storage medium having instructions encoded thereon that, when executed by the at least one processor, cause the at least one processor to perform a method of estimating a sequence of polymer units in a polymer, the method comprising:
• controlling translocation of the polymer through a nanopore using an enzyme;
• detecting, using a measurement circuit coupled to electrodes arranged on each side of the nanopore, a sequence of measurements of the polymer, each measurement being indicative of an ion current flowing through the nanopore during said translocation of the polymer through the nanopore;
• using at least one processor, coupled to a memory, to perform:
• accessing, in the memory, a probabilistic model comprising, for a set of possible k-mers, wherein a k-mer is a group of k polymer units where k is a positive integer:
• transition weightings each representing a probability of transition from an origin k-mer to a destination k-mer immediately subsequent in a sequence representing the sequence of polymer units, and wherein, when k is greater than one, transitions to destination k-mers that have a sequence in which the first k-1 polymer units are the same as the last k-1 polymer units of associated origin k-mers have greater probabilities than other transitions;
• and
• emission weightings each representing a probability of obtaining given values of ion current measurements for a respective k-mer of the set of possible k-mers;
• determining likelihoods, for each ion current measurement in the detected sequence of measurements of the polymer, that the ion current measurement was produced by respective k-mers of the set of possible k-mers, by optimizing a sequence of states of the probabilistic model based on the detected sequence of ion current measurements, the transition weightings, and the emission weightings;
• and
• determining an estimated sequence of polymer units in the polymer based on the likelihoods determined for each ion current measurement.