Cell-Free DNA Methylation Profiling for Noninvasive Tumor Detection
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Solution Overview
Problem
There is no practical means to study the fetal or tumor methylome noninvasively, making it difficult to monitor dynamic changes throughout pregnancy or during disease processes such as malignancies.
Innovation Solution
Noninvasive determination of methylation profiles using genome-wide bisulfite sequencing of cell-free DNA in maternal plasma to deduce fetal or tumor methylomes, utilizing fetal-specific alleles and size distribution of DNA fragments to identify methylation levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If invasive procedures are used to obtain fetal or tumor tissues for methylation analysis, then measurement precision is improved, but ease of operation deteriorates
Solution Approach 1:
The patent uses cell-free DNA in plasma as an intermediary substance that carries methylation information from fetal or tumor tissues without requiring direct tissue sampling. This intermediary approach allows indirect analysis of the target tissue's methylome through easily obtainable plasma samples, resolving the contradiction between accurate measurement and ease of operation
Solution Approach 2:
The invention creates a copy of the methylation information from fetal or tumor tissues by analyzing cell-free DNA fragments circulating in plasma. Instead of directly analyzing the original tissue, the method captures and analyzes methylation patterns in the plasma DNA copy, enabling noninvasive assessment while preserving measurement precision
2Ease of operation
If plasma DNA analysis is used to determine fetal or tumor methylome, then ease of operation is improved, but measurement precision deteriorates due to mixed DNA sources
Solution Approach 1:
The patent extracts and isolates fetal or tumor-specific DNA signals from the mixed plasma DNA population by identifying differentially methylated regions unique to the target tissue. This extraction process separates the signal of interest from background noise, enabling precise methylome determination despite the mixed DNA sources in plasma
Solution Approach 2:
The method focuses analysis on specific local regions (differentially methylated regions) that are characteristic of fetal or tumor tissues rather than analyzing the entire genome uniformly. By concentrating on these localized methylation patterns, the patent achieves high measurement precision for the target tissue's methylome while working with mixed plasma DNA
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
Enables comprehensive, noninvasive monitoring of fetal and tumor methylation patterns for screening, monitoring disease progression, and prognostication, applicable to various cancers and pregnancy-related pathologies.
Implementation Method 1
genome-wide bisulfite sequencing of cell-free DNA
Data Source
AI summary
Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.