Sequence-Based Mixed Nucleic Acid Analysis for Transplant Monitoring
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Solution Overview
Problem
Monitoring the health status of transplanted organs, tissues, and cells in transplant recipients is complex when they carry additional genomes from genetically distinct contributors, especially in cases of multiple transplants or pregnancies, due to the lack of prior genotype knowledge.
Innovation Solution
A computer-implemented method and system for determining the amount of contributor-derived cell-free nucleic acids in a mixed sample from a transplant recipient, using single nucleotide polymorphism (SNP) data and minor allele frequency (MAF) information to group and quantify nucleic acids from multiple genetically distinct contributors without prior genotype knowledge.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional monitoring methods are used in transplant recipients with multiple genomes from genetically distinct contributors, then the analysis becomes particularly complex and difficult, but the ability to accurately monitor transplant health status and detect rejection is compromised
Solution Approach 1:
The patent segments the complex mixed nucleic acid sample into distinguishable contributions from different genomic contributors by analyzing SNP allele frequencies. The computational method divides the analysis into steps: identifying contributors, determining their relationships, analyzing MAF patterns, and quantifying nucleic acid amounts from each contributor separately, thereby resolving the complexity while maintaining accuracy.
2Measurement precision
If prior genotype knowledge is required for accurate analysis, then the measurement precision improves, but the method loses applicability to recipients without prior genotyping data
Solution Approach 1:
The patent performs preliminary computational analysis by first identifying the genomic contributors and determining their relationships to the recipient before quantifying the nucleic acids. The method establishes the genetic framework and MAF patterns in advance, enabling accurate quantification without requiring pre-existing genotype data from the recipients or contributors.
3Measurement precision
If comprehensive genotyping of all contributors is performed, then the measurement precision improves, but the cost and time required for analysis increases
Solution Approach 1:
The patent extracts and analyzes only the necessary information from the mixed nucleic acid samples - specifically SNP allele frequency patterns - rather than performing comprehensive genotyping of all contributors. By focusing on the MAF patterns and contributor relationships, the method achieves accurate quantification with significantly reduced time and resource requirements compared to full genotyping approaches.
Data Source
AI summary
Disclosed herein are computer-implemented systems, kits, and methods for outputting an amount of contributor-derived nucleic acids in a biological sample, from a pregnant transplant recipient, that comprises nucleic acids from at least three genetically distinct contributors. The amount of contributor-derived nucleic acids may be useful in monitoring the status of a transplant for, e.g., assessing a risk of transplant rejection. In some examples, the at least three genetically distinct contributors may comprise a maternal genomic contributor, a fetal genomic contributor, and a transplant donor genomic contributor. For example, the systems and methods determine an estimated percentage of the contributor-derived nucleic acids and/or estimated percentage of the fetal-derived nucleic acids.