Normalized DNA Methylation Quantification via Transposon Markers
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for determining aberrant DNA methylation in tumor cells are limited by their inability to quantify and standardize this epigenetic change effectively, especially when comparing samples with different genomic settings, due to chromosomal anomalies and instability.
Innovation Solution
A process is developed to determine normalized DNA methylation levels by quantitatively assessing the presence of transposons and differentially methylated CpG dinucleotides, using bisulfite conversion and specific primers to normalize methylation levels across the genome.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If quantitative determination of DNA methylation is performed in tumor cells, then diagnostic accuracy is improved, but measurement precision deteriorates due to chromosomal anomalies and genomic instability
Solution Approach 1:
The patent introduces transposons as intermediary elements to bridge the gap between genomic instability and methylation measurement. Transposons serve as stable reference markers that can be reliably quantified even in the presence of chromosomal anomalies, enabling accurate normalization of methylation levels across heterogeneous tumor samples.
Solution Approach 2:
The patent changes the measurement approach by shifting from direct quantification of target gene methylation to indirect measurement through transposon-based normalization. This parameter transformation allows the system to overcome the precision limitations imposed by genomic instability while maintaining diagnostic reliability.
2Manufacturing precision
If standardized methylation determination is implemented, then comparability between samples is improved, but device complexity increases due to multi-step quantification process
Solution Approach 1:
The patent makes transposons universal reference markers that can be applied across different tissue types and tumor stages. The same transposon-based approach serves multiple functions: normalization, quantification, and comparison, thereby achieving standardization without proportionally increasing complexity.
Solution Approach 2:
The patent creates a simplified copy of the complex methylation landscape by using transposon sequences as proxy markers. Instead of measuring every CpG site in the genome, the system copies the essential information through transposon-based surrogate measurements, reducing complexity while maintaining standardization.
3Reliability
If direct comparison of methylation levels is performed, then diagnostic utility is improved, but loss of information increases due to chromosomal anomalies
Solution Approach 1:
The patent extracts the essential methylation information from the complex genomic background by isolating transposon sequences as reference markers. This extraction allows the system to compare methylation levels across samples while filtering out the noise introduced by chromosomal anomalies and genomic instability.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach allows for a standardized and quantitative assessment of DNA methylation, enabling direct comparison between samples and providing a representative methylation level that reflects the entire genome, even in the presence of chromosomal anomalies.
Implementation Method 1
using bisulfite conversion and specific primers to normalize methylation levels across the genome
Data Source
AI summary
The present invention provides oligonucleotides and processes for determining the normalized methylation level of DNA, and for determining the relative methylation level of DNA between at least two samples. The invention makes use of the random distribution of transposons in the genome. The disclosed oligonucleotides and processes are of importance, in particular, for clinical diagnostics.