Non-invasive fetal DNA methylation profiling via plasma analysis
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Solution Overview
Problem
Current methods lack a practical, non-invasive means to study and monitor the dynamic changes in fetal or tumor DNA methylation profiles throughout pregnancy or during disease processes, such as malignancies, due to the inaccessibility of human embryonic and fetal tissues and the invasive nature of existing diagnostic procedures.
Innovation Solution
The development of systems and methods to determine methylation profiles in plasma samples by comparing cell-free DNA from a fetus or tumor to a maternal or patient methylation profile, using techniques like genome-wide bisulfite sequencing and single nucleotide polymorphism analysis to identify fetal or tumor-specific alleles, allowing for non-invasive assessment of methylation levels and copy number variations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If invasive procedures are used to obtain fetal or tumor tissue samples, then direct access to the target tissue is achieved, but patient safety and comfort deteriorate due to procedural risks
Solution Approach 1:
The patent uses cell-free DNA in plasma as an intermediary substance that carries genetic information from the fetus or tumor without requiring direct tissue sampling. This intermediary allows indirect access to the target tissue's genetic material, eliminating the need for invasive procedures while still enabling methylation analysis
Solution Approach 2:
The invention analyzes a copy of the fetal or tumor genome that is present in the form of cell-free DNA fragments circulating in maternal plasma. Instead of sampling the original tissue directly, the method works with circulating DNA copies that contain the same genetic and epigenetic information
2Ease of operation
If plasma samples containing mixed DNA are analyzed, then non-invasive monitoring is enabled, but measurement precision deteriorates due to inability to distinguish fetal/tumor DNA from maternal DNA
Solution Approach 1:
The patent exploits local quality differences in methylation patterns at specific genomic loci to distinguish fetal/tumor DNA from maternal DNA. By focusing analysis on specific differentially methylated regions rather than the entire genome, the method can identify and quantify the minority genome component within the mixed plasma DNA sample
Solution Approach 2:
The invention measures changes in methylation parameters at specific genomic loci to differentiate between maternal and fetal/tumor DNA. By monitoring dynamic changes in methylation levels over time or in response to treatment, the method can track the fetal or tumor genome component despite the mixed DNA background
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.