Biological Sample Contamination Screening Using Homozygous Loci
Solution Overview
Problem
Existing methods for detecting cross-contamination in biological samples, particularly those involving cells from the same species, are costly, time-consuming, and resource-intensive due to the need for high-depth DNA sequencing to differentiate similar contaminating DNA from the source individual.
Innovation Solution
A method involving sequencing a biological sample at a first depth to identify homozygous loci, then sequencing a second sample at a lower depth and comparing nucleotides at these loci to detect mismatches, allowing for the detection of contamination using SNP analysis or omics data, and optionally processing the sample based on match or mismatch findings.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If high-depth DNA sequencing is used to detect low-level contamination, then measurement precision is improved, but cost and time consumption increase significantly
Solution Approach 1:
The method extracts and focuses analysis only on homozygous loci from the sequencing data, rather than analyzing the entire genome. This extraction of specific informative markers enables contamination detection at lower sequencing depths, reducing both time and cost while maintaining precision.
Solution Approach 2:
The invention applies different analysis strategies to different parts of the genomic data. By identifying and focusing on homozygous loci (where the individual has identical alleles), the method creates a localized high-quality detection region that is particularly sensitive to contamination, allowing reduced overall sequencing depth without sacrificing detection precision.
2Measurement precision
If high-depth DNA sequencing is used to detect low-level contamination, then measurement precision is improved, but cost increases significantly
Solution Approach 1:
The method extracts and focuses analysis only on homozygous loci from the sequencing data, rather than analyzing the entire genome. This extraction of specific informative markers enables contamination detection at lower sequencing depths, reducing both time and cost while maintaining precision.
Solution Approach 2:
The method uses partial sequencing coverage (lower depth) combined with focused analysis on specific homozygous loci. This partial action approach achieves sufficient detection precision without the excessive cost of high-depth whole-genome sequencing.
3Reliability
If conventional high-depth sequencing strategies are used, then contamination detection reliability is improved, but device complexity and resource requirements increase
Solution Approach 1:
The method extracts and focuses analysis only on homozygous loci from the sequencing data, rather than analyzing the entire genome. This extraction of specific informative markers enables contamination detection at lower sequencing depths, reducing both time and cost while maintaining precision.
Solution Approach 2:
The genomic data is segmented into homozygous and heterozygous loci, with the analysis specifically targeting the homozygous segment. This segmentation allows the method to achieve reliable contamination detection using simplified procedures focused on the most informative portion of the data.
Data Source
AI summary
The invention includes a method of screening a biological sample for contamination by sequencing a first biological sample at a first depth to generate a first nucleotide sequence; determining map coordinates for one or more homozygous loci in the first nucleotide sequence; sequencing a second biological sample at a second depth to generate a second nucleotide sequence, wherein the second depth is lower than the first depth; determining loci in the second nucleotide sequence at the determined map coordinates; and comparing the one or more homozygous loci in the first nucleotide sequence with the determined loci in the second nucleotide sequence.