NIPT Chromosome Aneuploidy Detection via CNV-Corrected Coverage
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Solution Overview
Problem
Current non-invasive prenatal testing (NIPT) methods for detecting chromosome aneuploidy face challenges with high false positive and false negative rates due to factors like confined placental mosaicism and copy number variations in the mother, which affect the accuracy of fetal DNA analysis.
Innovation Solution
A method involving high-throughput sequencing of peripheral blood cell-free DNA from pregnant women, where chromosomes are segmented into windows to calculate coverage statistics, identify chromosomal fragments with copy number variations, and correct coverage values using parameters to determine chromosome aneuploidy, thereby reducing false positives and negatives.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional NIPT methods are used for chromosome aneuploidy detection, then the detection can be performed non-invasively, but the false positive rate and false negative rate are high due to maternal copy number variations and confined placental mosaicism
Solution Approach 1:
The patent segments chromosomes into multiple windows and calculates coverage statistics for each window separately. This allows identification of localized copy number variations by comparing coverage across adjacent windows, thereby distinguishing true aneuploidy signals from maternal CNV background noise and improving detection accuracy
Solution Approach 2:
The patent introduces a correction model that uses maternal copy number variation data as an intermediary to adjust and correct chromosomal coverage statistics. This correction step removes the confounding effect of maternal CNVs before final aneuploidy determination, significantly reducing false positives and false negatives
2Measurement precision
If comprehensive sequencing of all chromosomes is performed, then complete chromosomal coverage is achieved, but the complexity of data analysis and calculation increases
Solution Approach 1:
By dividing the genome into chromosomal windows and processing coverage data segment by segment, the patent reduces the computational burden of analyzing entire chromosomes at once. This segmented approach maintains complete chromosomal coverage while making data processing more manageable and efficient
Solution Approach 2:
The patent performs preliminary correction of coverage statistics by identifying and accounting for maternal copy number variations before conducting the final aneuploidy detection. This preliminary action simplifies subsequent analysis by removing known sources of variation, reducing overall data processing complexity
Data Source
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Figure 3A~3B
AI summary
A kit, an apparatus, and a method for detecting chromosome aneuploidy. The method comprises: sequencing the peripheral blood cell-free DNA of a pregnant woman to be tested to produce sequencing data comprising all chromosomes; calculating a coverage for all of the chromosomes in the sequencing data by segmenting the chromosomes into windows so as to produce a pre-correction coverage for the each chromosome; calculating a ZCNV value using the number of unique sequences in each window and producing fragments with copy number variation of the pregnant woman on the basis of the magnitude of the ZCNV value; by utilizing the impact that the fragments with copy number variation have on the pre-correction coverage, correcting the pre-correction coverage to produce a corrected coverage; calculating a Zaneu value for the each chromosome by utilizing the corrected coverage of the each chromosome; and, if the absolute value of the Zaneu value is greater than or equal to 3, then it is determined that the chromosome has an aneuploidy.