Macromolecule Sequencing Noise Reduction via Cross-Correlation

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Solution Overview

Problem

Existing serial physical property sequencing methods for DNA and macromolecules are susceptible to significant noise sources, making them costly and inefficient, particularly in nanopore and scanning tunneling microscopy techniques, which hinder accurate and affordable genome sequencing.

Innovation Solution

The implementation of oversampling and cross-correlation techniques to reduce noise in sequencing data by determining signal values for macromolecules, specifically by cross-correlating multiple measured signals with associated time data to eliminate noise not in the same frequency and phase as the systematic signal, thereby increasing the signal-to-noise ratio.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If serial physical property sequencing methods are used for DNA and macromolecule sequencing, then sequencing capability is achieved, but noise significantly degrades measurement precision

Engineering Contradiction:
Improvesequencing accuracyVSAvoidnoise
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent applies periodic action by performing multiple sequential measurements of the same physical property at different time points. The method collects a series of measurements over time and uses cross-correlation analysis to identify periodic signal patterns while filtering out random noise, thereby improving sequencing accuracy without requiring additional hardware modifications.

Inventive Principle:
Principle #19Periodic action

2Reliability

If multiple measured signals are collected to improve signal-to-noise ratio, then sequencing reliability is enhanced, but data processing complexity increases

Engineering Contradiction:
Improvesequencing reliabilityVSAvoiddata processing complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces complex hardware systems with computational methods. Instead of using multiple complex measurement devices or sophisticated hardware filtering systems, the invention collects multiple signals from simpler measurements and uses cross-correlation algorithms to extract the true signal from noise, reducing hardware complexity while maintaining reliability.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If cross-correlation techniques are applied to reduce noise, then signal-to-noise ratio is improved, but computational time increases

Engineering Contradiction:
Improvesignal-to-noise ratioVSAvoidcomputational time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies preliminary action by performing optimizations and preprocessing steps before the main cross-correlation computation. The method includes pre-processing the measurement data to identify and exclude obviously erroneous readings, and optimizing the correlation calculation algorithm to reduce computational overhead, thereby minimizing time loss while maintaining precision improvement.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS9965586B2Noise reduction methods for nucleic acid and macromolecule sequencing
Publication Date: 2018.05.08 RGT UNIV OF CALIFORNIA
  • US9965586B2 patent drawing
  • US9965586B2 patent drawing
  • US9965586B2 patent drawing

AI summary

Methods, systems, and devices are disclosed for processing macromolecule sequencing data with substantial noise reduction. In one aspect, a method for reducing noise in a sequential measurement of a macromolecule comprising serial subunits includes cross-correlating multiple measured signals of a physical property of subunits of interest of the macromolecule, the multiple measured signals including the time data associated with the measurement of the signal, to remove or at least reduce signal noise that is not in the same frequency and in phase with the systematic signal contribution of the measured signals.