Cell-Free RNA Biomarker Panel for Accurate Trisomy 21 Screening
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Solution Overview
Problem
Current non-invasive prenatal screening methods for trisomy 21, such as NIPS, have inaccuracies due to undetected multiple fetuses, incorrect pregnancy dating, normal variation in ultrasound measurements, and maternal protein levels, leading to a significant chance of false positives and the need for invasive procedures like amniocentesis to confirm results.
Innovation Solution
The use of a combination of nucleic acid biomarkers, including ATP50, ICOSLG, DOP1B, PKNOX1, COL6A1, and GART, detected through hybridization with complementary primers or probes in cell-free nucleic acids from maternal plasma, to accurately identify trisomy 21 in a fetus.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If current non-invasive prenatal screening methods (NIPS) are used to detect trisomy 21, then the detection can be performed without invasive procedures, but the accuracy is reduced due to false positives from undetected multiple fetuses, incorrect pregnancy dating, and normal variation in measurements
Solution Approach 1:
The invention segments the detection approach by using multiple independent biomarkers (nucleic acid biomarkers, protein biomarkers, and ultrasound measurements) rather than relying on a single screening method. This segmentation allows each marker to contribute independently to the overall detection accuracy, reducing the impact of false positives from any single source and resolving the contradiction between non-invasive ease and detection precision.
2Measurement precision
If invasive procedures like amniocentesis are used to confirm screening results, then the detection accuracy is improved, but the risk of fetal injury or pregnancy loss increases
Solution Approach 1:
The invention introduces cell-free nucleic acids from maternal plasma as an intermediary substance that carries fetal genetic information without requiring direct access to the fetus. This intermediary enables accurate chromosomal analysis through non-invasive blood sampling, eliminating the need for invasive procedures like amniocentesis while maintaining high detection accuracy and avoiding fetal injury risks.
3Device complexity
If a single biomarker is used for screening, then the test simplicity is maintained, but the false positive rate increases due to normal variation and measurement errors
Solution Approach 1:
The invention merges multiple types of biomarkers (nucleic acid markers such as PAPP-A, hCG, and protein markers) into a single integrated screening test. This combination allows the system to cross-validate results across different marker types, reducing false positives caused by normal variation in any single marker while maintaining test simplicity through a unified reporting system.
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 significantly reduces false positives and eliminates the need for invasive procedures by providing a high detection rate and low false positive rate for trisomy 21, ensuring accurate identification of fetal chromosomal abnormalities.
Implementation Method 1
detecting in the cell free nucleic acids the presence of a combination of nucleic acid biomarkers comprising: ATP50, ICOSLG, DOP1B, PKNOX1, COL6A1, and GART, wherein the detecting comprises: contacting the cell free nucleic acids with primers or probes that are complementary to the nucleic acid biomarkers in the combination of nucleic acid biomarkers, and detecting hybridization between the primers or probes and the combination of nucleic acid biomarkers
Data Source
AI summary
Methods for detecting a Group of Biomarkers is provided herein. The translation profile of the Group of Biomarkers can be used for determining whether a subject, such as a fetus, has Down syndrome The methods include detecting one or more specific groups of biomarkers in a biological sample, and determining whether the expression of the biomarkers is altered when compared to expression of the biomarkers in one or more subjects that do not have trisomy 21 (e.g., a transcriptional standard). The biological sample can be a blood sample, and the biomarkers are cell free plasma RNAs.