Nucleic Acid Genotyping Mixed Samples Segmentation
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Solution Overview
Problem
Existing methods struggle to accurately genotype an unknown subject from mixed nucleic acid samples, as existing high-throughput nucleic acid sequencing and genotype arrays find it difficult to separate and analyze nucleic acid from multiple sources, especially when an additional sample from one subject cannot be obtained.
Innovation Solution
The methods involve obtaining sequence reads aligned to a reference genome, quantifying linked reference and alternative alleles, estimating the fraction of nucleic acid from the unknown subject, and generating genotype likelihoods to determine the genotype at a target genomic locus, even in mixed samples containing nucleic acid from multiple subjects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If high throughput nucleic acid sequencing and genotype arrays are used to generate genotype data, then large numbers of markers can be analyzed, but accurate genotyping of unknown subjects from mixed samples becomes difficult
Solution Approach 1:
The method segments the mixed sample analysis by first identifying known subjects, then separating their nucleic acid contributions from the total mixture to isolate and analyze the unknown subject's genotype independently
Solution Approach 2:
The method uses an intermediary computational approach that models the mixed sample as a combination of known and unknown subject genotypes, using statistical methods to deconvolute the contributing alleles
2Productivity
If nucleic acid from multiple subjects is analyzed together in a mixed sample, then sample processing efficiency is improved, but the ability to accurately genotype individual unknown subjects deteriorates
Solution Approach 1:
The method segments the analysis into distinct computational steps: identifying known subjects, quantifying their allele contributions, and then determining the unknown subject's genotype by subtraction and statistical modeling
Solution Approach 2:
The method changes the analytical parameters by using allele frequency distributions and genotype likelihood calculations instead of direct genotype calling, enabling accurate separation of mixed signals
Data Source
AI summary
The technology relates in part to methods and compositions for analyzing nucleic acid. In some aspects, the technology relates to methods and compositions for generating one or more genotypes for a sample. In some aspects, the technology relates to methods and compositions for generating one or more genotypes for a mixed sample.