Non-invasive Fetal Ploidy Detection via Cell-free Nucleic Acid Analysis
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Solution Overview
Problem
Current invasive prenatal testing methods, such as chorionic villus sampling and amniocentesis, pose risks to both mother and fetus, and there is a need for non-invasive techniques to detect fetal genetic variations and abnormalities early in pregnancy.
Innovation Solution
A method involving the analysis of circulating cell-free fetal nucleic acid in maternal plasma, which includes determining the fraction of fetal nucleic acid, calculating genomic section levels, and determining fetal ploidy using sequence reads mapped to a reference genome, allowing for non-invasive prenatal diagnosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If invasive prenatal testing methods (chorionic villus sampling, amniocentesis) are used to detect fetal genetic variations, then measurement precision is improved, but object-affected harmful factors increase due to risks to mother and fetus
Solution Approach 1:
The patent extracts fetal nucleic acid from maternal plasma, separating the diagnostic target (fetal genetic material) from the source of risk (invasive procedures). By analyzing cell-free fetal nucleic acid that naturally circulates in maternal blood, the method eliminates the need for invasive sampling while maintaining diagnostic capability for fetal genetic variations
Solution Approach 2:
The patent uses maternal plasma as an intermediary medium to access fetal genetic information. Instead of directly sampling fetal tissue through invasive procedures, the method analyzes fetal nucleic acid that has been released into the maternal circulation, using the maternal bloodstream as a safe intermediary for non-invasive diagnosis
2Object-affected harmful factors
If non-invasive methods analyzing cell-free fetal nucleic acid are used, then object-affected harmful factors are reduced, but measurement precision deteriorates due to low fetal nucleic acid fraction in maternal plasma
Solution Approach 1:
The patent analyzes copies of fetal genetic information present in the form of cell-free fetal nucleic acid fragments circulating in maternal plasma. Instead of requiring intact fetal cells or tissue, the method uses these molecular copies to infer fetal genetic status, enabling non-invasive diagnosis with sufficient precision
Solution Approach 2:
The patent transforms the diagnostic approach by changing from analyzing fetal cells directly to analyzing cell-free fetal nucleic acid in maternal plasma. This parameter change in the sample type and analysis target enables non-invasive testing while maintaining diagnostic accuracy through sophisticated molecular analysis methods
3Measurement precision
If genomic sequencing is performed on circulating cell-free nucleic acid to determine fetal ploidy, then measurement precision is improved, but device complexity and loss of time increase due to multiple processing steps
Solution Approach 1:
The patent segments the complex genomic analysis into manageable components: sequencing circulating cell-free nucleic acid, mapping reads to reference genome portions, calculating genomic section levels, and determining fetal ploidy from these levels. This segmentation allows systematic processing of complex data while maintaining precision
Solution Approach 2:
The patent performs preliminary mapping of sequence reads to reference genome portions and calculation of genomic section levels before final ploidy determination. These preliminary computational steps organize and prepare the data in advance, streamlining the overall analysis process and reducing complexity of the final interpretation
Data Source
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AI summary
The present invention relates to a system comprising one or more microprocessors and memory, which memory comprises instructions executable by the one or more microprocessors, and which instructions executable by the one or more processors are configured to: (a) determine a fraction of fetal nucleic acid in a sample, which sample comprises circulating cell-free nucleic acid from the blood of a pregnant female bearing a fetus; (b) obtain counts of sequence reads mapped to portions of a reference genome, which sequence reads are from the nucleic acid in the sample; (c) calculate a genomic section level for each of the portions of the reference genome, thereby providing calculated genomic section levels; and (d) determine fetal ploidy according to (i) the calculated genomic section levels for a subset of portions of the reference genome and (ii) the fraction of fetal nucleic acid determined in (a).