Nanopore Fractional Abundance Estimation Error Correction
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Solution Overview
Problem
Current methods for determining the fractional abundance of specific polynucleotide sequences in samples, such as those using nanopore devices, are prone to errors due to false positive and false negative detection errors and capture rate constant differentials, limiting their accuracy and reliability.
Innovation Solution
A method involving the use of control samples to correct for errors in nanopore data by generating and adjusting event signatures from target and reference analytes, employing mathematical methods like the Q-test, Support Vector Machine, and Expectation Maximization Algorithm to improve the estimation of true relative abundance in mixed unknown samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nanopore devices are used to determine fractional abundance of polynucleotide sequences, then sensitivity and single-molecule identification capability are improved, but measurement accuracy deteriorates due to false positive and false negative detection errors
Solution Approach 1:
The patent applies feedback by using control samples with known fractional abundances to generate correction factors that are fed back into the measurement process. The system measures control samples, compares detected abundances to true abundances, calculates correction factors, and applies these factors to correct measurements of unknown samples, thereby eliminating detection errors systematically
Solution Approach 2:
The patent implements preliminary action by performing measurements and error characterization on control samples before measuring unknown samples. The system pre-determines correction factors from control samples that account for false positives and false negatives, which are then applied to subsequent measurements of unknown samples to improve accuracy
2Measurement precision
If control samples and mathematical correction methods are implemented, then measurement accuracy is improved, but device complexity increases
Solution Approach 1:
The patent uses copying by creating control samples that replicate the measurement conditions for unknown samples. These control samples contain known quantities of target and reference analytes and are processed through the same nanopore device and analysis pipeline, allowing the system to copy the measurement process and characterize errors under identical conditions
Solution Approach 2:
The patent applies parameter changes by systematically varying the composition of control samples (different ratios of target to reference analytes) to characterize detection errors across different abundance levels. This allows the system to determine correction factors that are valid across a range of measurement conditions
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 of estimating the fractional abundance of target analytes in samples by accounting for errors, providing a more reliable and precise determination of relative abundance compared to existing methods.
Implementation Method 1
applying a voltage across a nanopore in a nanopore device to generate a detectable electronic signature and to induce translocation of charged analytes through said nanopore
Data Source
AI summary
Disclosed herein are methods and compositions for determining an improved estimate of the true fractional abundance of target analytes (e.g., specific polynucleotide sequences) in a sample using a nanopore sensor, e.g., by correcting errors inherent to identifying and correlating electrical signals to amounts of a target analyte or reference analyte in a sample.