A computer-implemented method of generating an estimate of a target sequence of nucleotides from one or more series of measurements taken by a measurement system comprising one or more nanopores, the or each series of measurements having been taken from a respective sequence of nucleotides of a polynucleotide during translocation of the polynucleotide through a nanopore, the respective sequence of nucleotides including the target sequence or a sequence having a predetermined relationship with the target sequence, each measurement being dependent on a k-mer, being k nucleotides of the respective sequence of nucleotides, where k is a positive integer, the method comprising storing a global model of the measurement system comprising: transition weightings representing the chances of transitions from origin k-mers to destination k-mers, and in respect of each identity of k-mer, emission weightings representing the chances of observing given values of measurements for that k-mer, characterised in that the method further comprises: adjusting the global model to derive one or more adjusted models by performing a parameterised transformation of the emission weightings and/or the transition weightings defined by at least one parameter that affects plural identities of k-mer, the at least one parameter being varied in a manner making reference to reference measurements taken using the measurement system such that the fit of the reference measurements to the adjusted model is improved over the fit of the reference measurements to the global model; from the one or more series of measurements, generating an estimate of the series of k-mers, corresponding to the target sequence of nucleotides, on which the measurements are dependent using the one or more adjusted models, based on the likelihood predicted by the adjusted model of the series of measurements being produced by sequences of k-mers; and from the estimate of the series of k-mers, generating the estimate of a target sequence of polymer units. the method comprising storing a global model of the measurement system comprising: transition weightings representing the chances of transitions from origin k-mers to destination k-mers, and in respect of each identity of k-mer, emission weightings representing the chances of observing given values of measurements for that k-mer, characterised in that the method further comprises: adjusting the global model to derive one or more adjusted models by performing a parameterised transformation of the emission weightings and/or the transition weightings defined by at least one parameter that affects plural identities of k-mer, the at least one parameter being varied in a manner making reference to reference measurements taken using the measurement system such that the fit of the reference measurements to the adjusted model is improved over the fit of the reference measurements to the global model; from the one or more series of measurements, generating an estimate of the series of k-mers, corresponding to the target sequence of nucleotides, on which the measurements are dependent using the one or more adjusted models, based on the likelihood predicted by the adjusted model of the series of measurements being produced by sequences of k-mers; and from the estimate of the series of k-mers, generating the estimate of a target sequence of polymer units. transition weightings representing the chances of transitions from origin k-mers to destination k-mers, and in respect of each identity of k-mer, emission weightings representing the chances of observing given values of measurements for that k-mer, characterised in that the method further comprises: adjusting the global model to derive one or more adjusted models by performing a parameterised transformation of the emission weightings and/or the transition weightings defined by at least one parameter that affects plural identities of k-mer, the at least one parameter being varied in a manner making reference to reference measurements taken using the measurement system such that the fit of the reference measurements to the adjusted model is improved over the fit of the reference measurements to the global model; from the one or more series of measurements, generating an estimate of the series of k-mers, corresponding to the target sequence of nucleotides, on which the measurements are dependent using the one or more adjusted models, based on the likelihood predicted by the adjusted model of the series of measurements being produced by sequences of k-mers; and from the estimate of the series of k-mers, generating the estimate of a target sequence of polymer units. adjusting the global model to derive one or more adjusted models by performing a parameterised transformation of the emission weightings and/or the transition weightings defined by at least one parameter that affects plural identities of k-mer, the at least one parameter being varied in a manner making reference to reference measurements taken using the measurement system such that the fit of the reference measurements to the adjusted model is improved over the fit of the reference measurements to the global model; from the one or more series of measurements, generating an estimate of the series of k-mers, corresponding to the target sequence of nucleotides, on which the measurements are dependent using the one or more adjusted models, based on the likelihood predicted by the adjusted model of the series of measurements being produced by sequences of k-mers; and from the estimate of the series of k-mers, generating the estimate of a target sequence of polymer units.