Nucleic Acid Sequence Data Scaling for Mutation Detection
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Solution Overview
Problem
Current DNA sequencing methods face challenges in accurately discriminating between homozygous and heterozygous sequences and in detecting low-level mutations, which limits their clinical applications and accuracy.
Innovation Solution
A method involving the creation of a relative height map from electropherogram signal data to normalize and scale nucleic acid sequence data, allowing for the identification of heterozygous mixtures and improved base calling accuracy by comparing signal strengths to expected heights, thereby enhancing the detection of mutations and sequence variations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional DNA sequencing methods are used, then the sequencing process is simple and widely applicable, but the accuracy in discriminating between homozygous and heterozygous sequences is insufficient
Solution Approach 1:
The patent creates a relative height map in advance by analyzing a panel of homozygous sequences to establish expected peak heights for each base position. This preliminary reference framework enables subsequent accurate detection of heterozygous sequences and low-level mutations without requiring complex real-time analysis during sequencing.
Solution Approach 2:
The relative height map serves as an intermediary reference standard that mediates between the raw sequencing data and the final interpretation. By comparing observed peak heights against this intermediate reference, the system can accurately identify heterozygous positions and mutations without direct complex comparison between multiple sequences.
2Measurement precision
If traditional sequencing analysis is used, then the base calling process is straightforward, but the ability to detect low-level mutations is limited
Solution Approach 1:
The patent transforms raw peak height measurements into normalized values by dividing by the expected height from the relative height map. This parameter transformation enables detection of low-level mutations as deviations from expected values, allowing sensitive detection without processing excessive data quantities.
3Measurement precision
If manual editing is used to improve sequence accuracy, then the precision of base calling can be improved, but the time consumption and labor requirements increase
Solution Approach 1:
The relative height map enables the sequencing system to self-correct and self-validate by automatically comparing observed peak heights against expected values. This self-service capability identifies heterozygous positions and mutations without requiring manual review, achieving high precision base calling while eliminating time-consuming manual editing.
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 increases the accuracy of base calling, particularly at heterozygous positions, and improves the ability to detect low-level mutations, reducing the need for manual editing and enhancing the quantitation of mutations in DNA sequencing data.
Implementation Method 1
separating the fragments by size to determine what order they are in can be performed by a number of well known techniques
Data Source
AI summary
A method of analyzing nucleic acid sequence data produced by automated sequencer comprises scaling the data according to a map of relative heights of homozygous base data. An apparatus for conducting the method comprises means for scaling the data according to a map of relative heights of homozygous base data.