Immune Cell DNA Methylation Profiling for Precise Cell-Type Quantification
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods for analyzing liquid biopsies, such as detecting circulating tumor DNA from early-stage cancer, are challenging due to low abundance and variability in nucleic acid release, and current immune cell type differentiation methods fail to distinguish between types like naïve and activated lymphocytes, limiting accurate disease detection and treatment.
Innovation Solution
A method involving DNA methylation analysis of immune cells, using differentially methylated regions and next-generation sequencing to quantify specific immune cell types, including partitioning and capturing DNA with target-specific probes to enhance differentiation and detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If DNA methylation analysis is used to distinguish immune cell types, then measurement precision is improved, but device complexity increases due to the need for partitioning, capturing, and next-generation sequencing
Solution Approach 1:
The DNA analysis process is segmented into distinct functional stages: partitioning DNA by methylation status, capturing target regions with probes, and sequencing. This segmentation allows complex differentiation of immune cell types to be achieved through manageable, sequential steps rather than a single complex procedure
Solution Approach 2:
Target-specific probes serve as intermediaries between the DNA sample and the sequencing process. These probes capture and enrich for differentially methylated regions, acting as a mediator that simplifies the overall process by focusing the analysis on informative genomic regions rather than processing entire genomes
2Productivity
If complete blood counts and microarray-based profiling are used, then productivity is improved for detecting cell types, but measurement precision deteriorates because these methods cannot distinguish between certain types of immune cells
Solution Approach 1:
Instead of treating all immune cell DNA uniformly, the method applies local quality analysis by targeting specific genomic regions with different methylation patterns. Each immune cell type has a distinct methylation signature at specific loci, allowing precise differentiation while maintaining efficiency through targeted rather than comprehensive analysis
3Ease of operation
If liquid biopsy analysis is performed to detect circulating tumor DNA, then ease of operation is improved through noninvasive sampling, but measurement precision deteriorates due to low abundance and variable recovery of nucleic acids
Solution Approach 1:
The method performs preliminary action by partitioning and capturing DNA based on methylation status before sequencing. This pre-processing step enriches for informative regions and compensates for the low abundance and variability of nucleic acids in liquid biopsies, improving detection precision while maintaining the noninvasive sampling advantage
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
Improves the accuracy of disease detection by distinguishing between immune cell types, providing more precise diagnostic information for conditions like cancer and enabling better treatment strategies.
Implementation Method 1
genomic regions that are differentially methylated between specific immune cell types and other blood cells and methyl binding assays to profile the methylation status of DNA fragments from these regions
Data Source
AI summary
Provided herein is a DNA analysis method for detecting and quantifying immune cell types from which the DNA originated. Provided herein are also methods for determining the likelihood that a subject has a disease or condition, such as cancer.