US 12,321,837 B2
Systems and methods for improved nanopore-based analysis of nucleic acids
Jens H. Gundlach, Seattle, WA (US); Matthew Noakes, Seattle, WA (US); and Henry D. Brinkerhoff, Seattle, WA (US)
Assigned to UNIVERSITY OF WASHINGTON, Seattle, WA (US)
Appl. No. 17/430,695
Filed by University of Washington, Seattle, WA (US)
PCT Filed Feb. 14, 2020, PCT No. PCT/US2020/018426
§ 371(c)(1), (2) Date Aug. 12, 2021,
PCT Pub. No. WO2020/168286, PCT Pub. Date Aug. 20, 2020.
Claims priority of provisional application 62/805,870, filed on Feb. 14, 2019.
Prior Publication US 2022/0366313 A1, Nov. 17, 2022
Int. Cl. G06N 20/10 (2019.01); C12Q 1/6869 (2018.01); G01N 33/487 (2006.01); G06N 20/20 (2019.01)
CPC G06N 20/10 (2019.01) [C12Q 1/6869 (2013.01); G01N 33/48721 (2013.01); G06N 20/20 (2019.01)] 20 Claims
OG exemplary drawing
 
1. A computer-implemented method of determining an identity of one or more monomer subunit residues of a polymer analyte, the method comprising:
transmitting, by a computing system, an instruction to a nanopore system that causes a voltage source of the nanopore system to generate a variable voltage between a first conductive liquid medium and a second conductive liquid medium;
receiving, by the computing system, a raw current signal generated as a polymer analyte translocates through a nanopore of the nanopore system in response to the variable voltage;
detecting, by the computing system, change points in the raw current signal to determine a series of states, wherein detecting change points in the raw current signal includes determining basis functions derived from a dimensionality-reduced version of the raw current signal;
performing, by the computing system, capacitance compensation on the raw current signal for each state to create an ionic current-vs-voltage curve for each state;
converting, by the computing system, the ionic current-vs-voltage curves to conductance-vs-voltage curves;
performing, by the computing system, filtering for the series of states to create a series of filtered states; and
determining, by the computing system, the identity of one or more monomer subunit residues of the polymer analyte based on the series of filtered states.