Low-Pass Genomic Sequencing for Rapid Parentage Analysis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for paternity/maternity testing, such as high read-depth genome sequencing and PCR-based methods, are costly and labor-intensive, and low-pass genome sequencing faces challenges in accurately detecting single-nucleotide variants due to insufficient coverage and error-prone genotyping.
Innovation Solution
An analytical pipeline using low-pass genome sequencing with 1-fold to 15-fold read-depth, aligning sequence reads to a human genome reference, identifying single-nucleotide variants, and calculating an inconsistent rate of base-type inheritance to determine paternity/maternity through duo-based and trio-based analysis models.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If high read-depth genome sequencing is used for paternity testing, then measurement precision is improved, but device complexity and cost increase
Solution Approach 1:
The patent extracts only the necessary genetic information for paternity testing by using a targeted panel of 100-1000 SNPs instead of sequencing the entire genome at high depth. This selective extraction maintains measurement precision for the specific application while dramatically reducing device complexity and cost.
Solution Approach 2:
The patent employs low-pass genome sequencing with read depths of 0.1-4 folds, which is insufficient for de novo variant discovery but adequate for genotyping known SNPs. This disposable-level sequencing depth reduces cost and complexity while maintaining sufficient precision for paternity testing when applied to predetermined SNP panels.
2Productivity
If low-pass genome sequencing is used for paternity testing, then cost and time are reduced, but measurement precision deteriorates due to insufficient coverage
Solution Approach 1:
The patent performs preliminary selection of 100-1000 SNPs that are predetermined and known before sequencing. By pre-selecting the exact genomic positions to analyze, the method ensures that even with low read depth (0.1-4 folds), there is sufficient coverage at these specific sites to achieve accurate genotyping for paternity testing.
Solution Approach 2:
The patent changes the sequencing depth parameter from high (required for de novo variant discovery) to low (0.1-4 folds), which is sufficient when combined with targeted SNP panel analysis. This parameter change, coupled with increasing the number of SNPs analyzed from hundreds to thousands, maintains measurement precision while improving productivity.
3Measurement precision
If PCR-based methods with short tandem repeats are used for paternity testing, then measurement precision is improved, but loss of time increases due to labor-intensive procedures
Solution Approach 1:
The patent replaces the mechanical PCR amplification and gel electrophoresis procedures with automated next-generation sequencing technology. This substitution eliminates manual laboratory operations, automates the genotyping process, and enables high-throughput analysis, thereby maintaining measurement precision while dramatically reducing loss of time and labor intensity.
Data Source
AI summary
The subject invention pertains to the field of healthcare informalities and provides information and communication (ICT) technology useful for methods and tools for paternity and/or maternity testing. An analytical pipeline based on low-pass GS (e.g., 1-fold read depth), referred to herein as LpPat, is provided for paternity and/or maternity testing (e.g., with trio-based and duo-based analytical modes). By down-sampling the read-depth from 10 trios with confirmed paternity and maternity, an optimal read depth of 1-fold is demonstrated across other sequencing parameters with a turnaround time for the analysis of less than one hour. The robust performance has been validated by another 170 trios sequenced from different library construction methods and platforms. The algorithmic analysis provides a rapid, cost effective, and sequencing-platform-neutral paternity and/or maternity test, based on low-pass genetic sequencing.