Nanopore Polymer Analysis via Feature Vector Extraction

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Solution Overview

Problem

Current nanopore measurement systems face challenges in reliably determining the sequence of polymers due to overlapping signals from different k-mers, especially with high numbers of k-mers, leading to difficulties in resolving measurements and deriving accurate sequence information.

Innovation Solution

A method is developed to analyze time-ordered series of measurements by deriving a feature vector of time-ordered features representing characteristics of the measurements, determining similarity between this feature vector and others, which allows for polymer analysis without the need to resolve every single polymer unit sequence, thereby reducing system complexity and increasing measurement system flexibility.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If measurements are made to determine complete polymer sequence information, then measurement precision is improved, but device complexity increases due to the need to resolve overlapping signals from many k-mers

Engineering Contradiction:
Improvesequence determination accuracyVSAvoidsignal resolution complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts only the essential features needed for polymer analysis from the complete measurement signal. Instead of attempting to resolve all k-mer signals to determine complete sequence information, the system identifies and extracts key temporal features (such as translocation duration, current blockage characteristics, and signal patterns) that are sufficient for diagnostic and classification purposes. This extraction approach maintains measurement precision for the required applications while dramatically reducing device complexity by avoiding the need to resolve all overlapping k-mer signals.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies partial action by obtaining sufficient measurement information without achieving complete sequence determination. The system performs partial analysis of the polymer signal, focusing on extracting features that provide adequate information for the intended applications (diagnostic, classification, identification) rather than attempting the excessive task of fully resolving every k-mer contribution to the signal. This partial approach reduces complexity while maintaining sufficient precision for practical use.

Inventive Principle:
Principle #16Partial or excessive action

2Measurement precision

If complete sequence information is obtained by resolving all polymer units, then measurement precision is improved, but loss of time increases due to the complexity of analyzing overlapping signals

Engineering Contradiction:
Improvesequence information accuracyVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts key temporal and signal features from the nanopore measurement data without attempting to fully resolve all overlapping k-mer signals. By identifying and extracting essential features such as translocation duration, current blockage depth, and characteristic signal patterns, the system achieves sufficient measurement precision for polymer analysis while dramatically reducing the time required for data processing and analysis compared to complete sequence determination methods.

Inventive Principle:
Principle #2Taking out (Extraction)

3Device complexity

If the measurement system is simplified to avoid resolving all k-mers, then device complexity is reduced, but measurement precision deteriorates due to overlapping signals

Engineering Contradiction:
Improvesystem complexityVSAvoidpolymer analysis accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent implements partial action by obtaining sufficient measurement information without achieving complete sequence determination. The system performs partial analysis focused on extracting features that provide adequate information for diagnostic and classification applications. This approach maintains measurement precision sufficient for practical use while avoiding the excessive complexity of fully resolving all k-mer signals, effectively finding the optimal balance between precision and simplicity for the intended applications.

Inventive Principle:
Principle #16Partial or excessive action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach enables effective analysis of polymers by converting raw signal measurements into feature vectors, providing useful information for diagnostic and scientific applications without requiring complete sequence information, thus simplifying the measurement system and enhancing its operational efficiency.

Implementation Method 1

An applied potential is used to drive the DNA molecule from one side of the membrane to the other

Methodology Applied
Scientific EffectElectrophoresis: Electrophoresis

Implementation Method 2

The applied potential across the electrodes also drives the electrolyte through the pore and generates a current

Methodology Applied
Scientific EffectIon transport: Electro-Osmotic Flow

Implementation Method 3

When material passes through the pore it modifies the flow of ions which is directly observed in the current measurement. The degree of current block and the duration the material spends in the nanopore are indicative of its identity

Methodology Applied
Scientific EffectCurrent blockage:

Data Source

PatentUS20240264143A1Analysis of measurements of a polymer
Publication Date: 2024.08.08 OXFORD NANOPORE TECH LTD
  • US20240264143A1 patent drawing
  • US20240264143A1 patent drawing
  • US20240264143A1 patent drawing

AI summary

A time-ordered series of measurements of a polymer made during translocation of the polymer through a Nanopore are analysed. The measurements are dependent on the identity of k-mers in the Nanopore, a k-mer bring k polymer units of the polymer, where k is a positive integer. The method involves deriving, from the series of measurements, a feature vector of time-ordered features representing characteristics of the measurements; and determining similarity between the derived feature vector and at least one other feature vector.