Chromosomal Aneuploidy Detection Using Reference Genome Bins
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Solution Overview
Problem
Existing methods for detecting chromosomal aneuploidy are prone to false positives and negatives due to environmental parameter inconsistencies, leading to high detection and maintenance costs.
Innovation Solution
A method using chromosome bin sequences and sequencing depth sequences, determined from reference genome data and whole genome sequencing data, to perform a non-parametric test for aneuploidy detection, independent of environmental parameter consistency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional detection methods (z-score, NCVs, GWNS) are used to determine chromosomal aneuploidy by comparing sample indicators to normal sample distributions, then detection can be performed with existing algorithms, but environmental parameter inconsistencies cause false positives and negatives, requiring large amounts of time and resources for parameter matching
Solution Approach 1:
The patent extracts the core detection logic from environmental parameter dependencies by using a fixed reference genome-based chromosome bin sequence. Instead of comparing sample indicators to normal sample distributions that require parameter matching, the method extracts chromosomal DNA sequences, divides them into bins, and compares bin number ratios directly against a predetermined reference, eliminating the need for environmental parameter consistency and reducing time/resource consumption for parameter matching
Solution Approach 2:
The patent performs preliminary action by pre-establishing the chromosome bin sequence based on the human reference genome before actual detection. The reference sequence is constructed in advance with predetermined bin divisions and number ratios, so that during detection, only the sample's chromosomal DNA needs to be sequenced and compared, without requiring real-time parameter adjustment or matching to normal sample distributions
2Measurement precision
If environmental parameter consistency is required between sample and normal samples, then indicator distribution matching can be achieved, but hardware limitations and operator variations make consistency difficult, leading to false results
Solution Approach 1:
The patent applies segmentation by dividing chromosomal DNA sequences into discrete bins along the chromosome. Instead of treating the entire chromosome as a single indicator that requires distribution matching, the chromosome is segmented into multiple bins, and the number ratio of bins is calculated. This segmentation transforms the measurement into a discrete, countable metric that is independent of environmental parameters and can be directly compared to the reference genome
Solution Approach 2:
The patent changes the detection parameter from continuous indicator values (sequencing depth, coverage) that require distribution matching to a discrete parameter (bin number ratio) that is inherently normalized. By changing from comparing continuous measurements to comparing discrete counts against a fixed reference, the method achieves adaptability to different hardware and operator conditions while maintaining measurement precision
Data Source
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AI summary
Provided are a method and apparatus for detecting chromosomal aneuploidy, a device and a storage medium. The method includes: determining a chromosome bin sequence of a chromosome under test according to reference genome nucleic acid data of a human reference genome; determining a sequencing depth sequence of the chromosome under test according to whole genome sequencing data of a nucleic acid sample under test, performing a non-parametric test to determine an aneuploidy detection result of the chromosome under test in the nucleic acid sample under test. Relatively high detection accuracy is achieved, the problem is solved of dependence of a method for detecting chromosomal aneuploidy on indicator distribution in a normal sample, and detection and maintenance costs of chromosomal aneuploidy are reduced.