Fetal Chromosome Copy Number Detection via GC-Corrected DNA Sequencing
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Solution Overview
Problem
Current methods for detecting copy number abnormalities of fetal or tumor chromosomes are invasive, costly, or have low accuracy due to the low concentration of fetal DNA in maternal plasma, making it difficult to non-invasively and accurately determine chromosomal copy numbers, especially during early fetal development or in tumor diagnosis.
Innovation Solution
A method and kit utilizing the linear relationship between GC content and DNA segment ratios in maternal plasma to correct and determine chromosomal copy numbers, involving DNA sequencing and library preparation, which includes separating and sequencing DNA segments within specific length ranges to differentiate between fetal and maternal DNA, thereby improving detection accuracy and reducing false negatives.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If high-throughput sequencing techniques are used to detect fetal DNA in maternal plasma, then the detection coverage and ability to detect partial copy number changes improve, but the sequencing cost increases significantly
Solution Approach 1:
The patent extracts and analyzes only the size distribution characteristics of fetal DNA fragments (100-250bp range) from the complex maternal plasma DNA sample, rather than sequencing all DNA. This selective extraction of size information allows cost-effective detection of fetal DNA without requiring expensive whole-genome sequencing, while still achieving accurate copy number detection
Solution Approach 2:
The patent changes the detection parameter from sequence content analysis (requiring high-cost sequencing) to fragment size distribution analysis (achievable with lower-cost methods). By measuring the length distribution of DNA fragments and comparing fetal-specific size ranges against maternal DNA, the patent achieves accurate detection at reduced cost
2Ease of operation
If the content of fetal DNA in maternal plasma is low (only 5% during early development), then the non-invasive detection capability is maintained, but the detection accuracy decreases due to background maternal DNA
Solution Approach 1:
The patent applies local quality by focusing analysis on the specific size range (100-250bp) where fetal DNA fragments are concentrated, rather than analyzing all DNA fragments uniformly. This size-specific analysis enhances the signal from fetal DNA while filtering out the overwhelming maternal DNA background, achieving accurate detection despite low fetal DNA content
Solution Approach 2:
The patent uses partial action by analyzing only the relevant size fraction of DNA fragments (100-250bp) that contain fetal DNA signals, rather than processing the entire DNA population. This selective partial analysis improves detection accuracy by concentrating computational and analytical resources on the informative subset of data
3Measurement precision
If DNA segments of specific length ranges are separated and sequenced to differentiate fetal and maternal DNA, then the detection accuracy improves, but the device complexity increases
Solution Approach 1:
The patent introduces size distribution analysis as an intermediary step between sample collection and copy number determination. By first characterizing the size distribution of DNA fragments and identifying the fetal-specific size range, the method creates an intermediate layer of information that simplifies subsequent analysis and reduces the complexity of direct sequencing and interpretation
Data Source
AI summary
The invention relates to a kit, a device and a method for detecting the copy number of fetal chromosomes and tumor cell chromosomes. The method for detecting the copy number of fetal chromosomes or tumor cell chromosomes of the invention includes the following steps: collecting maternal plasma or plasma of tumor patient; separating the plasma from blood cells in blood; preparing Deoxyribonucleic Acids (DNA) in the plasma into a sequencing library; sequencing the DNA sequencing library; comparing a sequencing result with a genomic sequence map to determine which chromosome the DNA sequence comes from and the length of each DNA sequence; and calculating the ratio of the DNA segments from the chromosomes to be detected to all DNA segments in the same sample by a sequencing and comparison result of DNA, correcting the ratio according to a GC content of the DNA segments from the chromosomes to be detected, and calculating the variation of the corrected ratio of the DNA segments from the chromosomes to be detected in a sample to be detected, and determining the copy number of the chromosomes to be detected according to degree of variation.