Bead Position Detection in Next-Generation Sequencing Images

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Solution Overview

Problem

In next-generation sequencing (NGS) technologies, accurately distinguishing true positive bead positions from false positive positions in digital images is challenging due to noise and artifacts, which affects the precision and reliability of genetic information detection.

Innovation Solution

A method and system that determine pixel positions with local maximum intensity values, calculate variance, weight intensity values, create a histogram, select a threshold from local minima relative to the global maximum, and use it to discriminate true positive from false positive positions, with optional sub-pixel positioning and uneven illumination correction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional bead detection methods are used in NGS, then the detection process is simple, but the accuracy of distinguishing true positive from false positive bead positions deteriorates due to noise and artifacts

Engineering Contradiction:
Improveaccuracy of bead position detectionVSAvoidcomplexity of detection method
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The detection method is segmented into multiple distinct steps: identifying local maxima, calculating variance for each maximum, weighting intensity values by variance, creating histograms, and selecting thresholds from local minima. This segmentation allows each step to address specific aspects of the detection problem, improving overall accuracy while maintaining systematic complexity management.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The method applies partial action by focusing computational resources only on pixels identified as local maxima rather than processing the entire image. This selective approach reduces unnecessary computations while maintaining detection accuracy, effectively balancing precision with computational efficiency.

Inventive Principle:
Principle #16Partial or excessive action

2Reliability

If strict thresholding is applied to filter noise, then false positive positions are reduced, but true positive positions may be lost due to overly aggressive filtering

Engineering Contradiction:
Improvereliability of positive position identificationVSAvoidloss of true positive positions
Core Design Contradiction:
ReliabilityVSLoss of information

Solution Approach 1:

The method dynamically adjusts the threshold parameter based on the histogram distribution of variance-weighted intensity values. By selecting thresholds from local minima in the histogram rather than using fixed thresholds, the method adapts to the specific characteristics of each image, maintaining high reliability while preserving true positive positions that would otherwise be lost.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The histogram analysis provides feedback about the distribution of intensity values, which is then used to inform threshold selection. This feedback mechanism allows the system to automatically adjust its discrimination criteria based on the actual data characteristics, ensuring that true positive positions are not lost while still filtering false positives effectively.

Inventive Principle:
Principle #23Feedback

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 enhances the accuracy and reliability of bead detection by effectively filtering out noise and artifacts, ensuring robust and precise identification of true positive bead positions, thereby improving the overall sequencing process.

Implementation Method 1

Frequently, such electronic devices detect fluorescent signals emitted from the sample probes. This is possible when molecules, such as nucleic acids or proteins, have been labelled with fluorescent compounds such as dyes.

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS10733707B2Method for determining the positions of a plurality of objects in a digital image
Publication Date: 2020.08.04 QIAGEN GMBH
  • US10733707B2 patent drawing
  • US10733707B2 patent drawing
  • US10733707B2 patent drawing

AI summary

The present invention relates to a method and a system for determining the positions of a plurality of objects in a digital image by discriminating true positive positions of the plurality of objects from false positive candidate positions of the plurality of objects. In particular, the invention relates to a method for determining the positions of a plurality of objects in a digital image by discriminating true positive positions of the plurality of objects from false positive candidate positions of the plurality of objects, the plurality of objects being configured to receive molecules comprising genetic information.