Parental Genotype Reconstruction for Noisy Embryo Copy-Number Analysis
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Solution Overview
Problem
Current genetic data measurement techniques for pre-implantation and prenatal diagnosis are unreliable, costly, and prone to errors such as allele drop-out, especially when analyzing single cells or small DNA samples, which can lead to incorrect genetic screening results and ethical dilemmas.
Innovation Solution
A system that uses secondary genetic data from related individuals, such as parents and siblings, to reconstruct and clean noisy genetic data from embryos or fetuses, improving the accuracy of chromosome copy number determination and aneuploidy detection by creating hypotheses based on probabilistic analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If genetic data is measured from single cells or small DNA samples, then the cost is reduced and the technique becomes more practical, but the reliability and measurement precision deteriorate due to allele drop-out and measurement errors
Solution Approach 1:
The patent introduces parental genetic data as an intermediary to mediate the interpretation of noisy embryo genetic data. By using parental genotypes as a reference framework, the system can distinguish true allele drop-outs from actual genetic abnormalities, thereby maintaining reliability while analyzing single cells
Solution Approach 2:
The system implements feedback by using parental genetic information to validate and correct embryo genetic measurements. The parental data serves as a feedback mechanism that allows the system to identify and correct measurement errors, improving reliability without requiring more complex sampling
2Measurement precision
If traditional genetic screening methods are used on single cells, then the measurement precision is limited by allele drop-out, but the device complexity and cost remain high
Solution Approach 1:
The patent merges parental genetic data with embryo genetic data into a unified analysis framework. This combination allows the system to leverage the redundancy of parental information to compensate for measurement errors in the embryo sample, improving precision without requiring more complex measurement devices
Solution Approach 2:
The system performs preliminary analysis by first establishing parental genotype profiles before interpreting embryo genetic data. This preliminary action creates a reference framework that simplifies the subsequent analysis of embryo samples, reducing the need for complex real-time decision-making during measurement
3Measurement precision
If comprehensive genetic screening is performed on multiple parameters, then the measurement precision and diagnostic capability improve, but the cost and time required for analysis increase
Solution Approach 1:
The patent applies partial action by focusing genetic screening on specific chromosomes or genetic regions of clinical interest rather than performing exhaustive whole-genome analysis. The parental data framework enables targeted analysis that achieves sufficient diagnostic accuracy while reducing time and cost
Solution Approach 2:
The parental genetic data framework serves multiple functions simultaneously: it provides a reference for allele identification, enables detection of various chromosomal abnormalities, and allows for both aneuploidy and monosomy detection. This multi-functionality achieves comprehensive diagnostic capability without proportionally increasing analysis time
Data Source
AI summary
Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.