A system or instrument comprising: a sequencing cell that includes a nanopore (216, 316), the nanopore (216, 316) configured to receive a tag that is connected to a nucleotide, thereby creating a threading event; a signal generator configured to apply an alternating signal across the nanopore (216, 316) of the sequencing cell, each cycle of the alternating signal comprising a first portion and a second portion, wherein voltage levels of the second portion are opposite of a reference voltage than voltage levels of the first portion; an analog-to-digital converter configured to acquire a first set of voltage data during the first portion (520 of a plurality of cycles of the alternating signal, wherein each data point of the first set of voltage data corresponds to a value of a resistance of the nanopore (216, 316) at a different time, where the resistance of the nanopore (216, 316) changes when the tag is received within the nanopore (216, 316); and characterized in that the system or instrument further comprises a digital processor configured to: determine a time-shifted set of voltage data (710, 720) from the first set of voltage data, wherein each cycle of data points of the first set of voltage data and the time-shifted set of voltage data. 720) includes a specified number of data points; compute difference data values by computing differences between data points of the first set of voltage data and corresponding data points of the time-shifted set of voltage data (710, 720); identify a plurality of noise data points as data points having difference data values that are larger than a first threshold value (1113, 1117); and determining a denoised first set of voltage data by removing the plurality of noise data points from the first set of voltage data. a sequencing cell that includes a nanopore (216, 316), the nanopore (216, 316) configured to receive a tag that is connected to a nucleotide, thereby creating a threading event; a signal generator configured to apply an alternating signal across the nanopore (216, 316) of the sequencing cell, each cycle of the alternating signal comprising a first portion and a second portion, wherein voltage levels of the second portion are opposite of a reference voltage than voltage levels of the first portion; an analog-to-digital converter configured to acquire a first set of voltage data during the first portion (520 of a plurality of cycles of the alternating signal, wherein each data point of the first set of voltage data corresponds to a value of a resistance of the nanopore (216, 316) at a different time, where the resistance of the nanopore (216, 316) changes when the tag is received within the nanopore (216, 316); and characterized in that the system or instrument further comprises a digital processor configured to: determine a time-shifted set of voltage data (710, 720) from the first set of voltage data, wherein each cycle of data points of the first set of voltage data and the time-shifted set of voltage data. 720) includes a specified number of data points; compute difference data values by computing differences between data points of the first set of voltage data and corresponding data points of the time-shifted set of voltage data (710, 720); identify a plurality of noise data points as data points having difference data values that are larger than a first threshold value (1113, 1117); and determining a denoised first set of voltage data by removing the plurality of noise data points from the first set of voltage data. determine a time-shifted set of voltage data (710, 720) from the first set of voltage data, wherein each cycle of data points of the first set of voltage data and the time-shifted set of voltage data. 720) includes a specified number of data points; compute difference data values by computing differences between data points of the first set of voltage data and corresponding data points of the time-shifted set of voltage data (710, 720); identify a plurality of noise data points as data points having difference data values that are larger than a first threshold value (1113, 1117); and determining a denoised first set of voltage data by removing the plurality of noise data points from the first set of voltage data.