Differentially Methylated Regions for Embryo–Adult State Detection
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Solution Overview
Problem
Current methods lack sensitivity for quantifying the extent of reprogramming of somatic cells to pluripotency and partial in vivo reprogramming to reverse aging and induce tissue regeneration, and there is a need for improved markers to determine the epigenetic state of cells during in vitro and in vivo transitions, particularly in the context of cancer diagnosis and treatment.
Innovation Solution
The use of differentially methylated regions (DMRs) of DNA associated with the embryonic-fetal transition (EFT) as markers to assess the developmental status of cells, which are hypermethylated in pre-fetal cells, providing insights into the regenerative potential and sensitivity to apoptosis, and can be used to diagnose and treat various cancer types by targeting cells to a more mature fetal or adult phenotype.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods are used to assess reprogramming extent, then the basic capability is maintained, but sensitivity and measurement precision are insufficient
Solution Approach 1:
The patent changes the measurement parameter from generic reprogramming markers to specific differentially methylated regions (DMRs) associated with embryonic-fetal transition. By focusing on methylation status at specific genomic loci that are hypermethylated in pre-fetal cells, the method achieves higher sensitivity and precision in quantifying reprogramming extent and determining epigenetic state.
Solution Approach 2:
The patent replaces general reprogramming assessment methods with an epigenetic-based measurement system using DNA methylation analysis. This substitution enables more precise detection of cellular developmental state and reprogramming status through molecular markers rather than conventional methods.
2Measurement precision
If DMR markers are used to identify embryonic phenotype cells, then diagnosis accuracy improves, but the complexity of the assay increases
Solution Approach 1:
The patent segments the complex epigenetic profile into specific differentially methylated regions (DMRs) that are characteristic of embryonic-fetal transition. By identifying and analyzing these discrete genomic regions rather than the entire genome, the method achieves high diagnosis accuracy while managing assay complexity through targeted analysis of specific markers.
Solution Approach 2:
The patent identifies DMRs that serve as pan-cancer markers, making them universally applicable across different cancer types. This multi-functionality allows the same set of DMR markers to be used for diagnosing various cancer types, reducing the need for multiple specialized assays and thereby managing overall system complexity.
3Adaptability or versatility
If in vitro reprogramming is performed to generate iPS cells, then cellular pluripotency is achieved, but epigenetic abnormalities and incomplete reprogramming occur
Solution Approach 1:
The patent employs DMR analysis as a feedback mechanism to assess the completeness of reprogramming and identify epigenetic abnormalities in iPS cells. By measuring methylation status at specific DMRs, the method provides quantitative feedback on reprogramming quality, enabling monitoring and potential optimization of the reprogramming process to achieve more complete epigenetic reprogramming.
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
The DMR markers provide pan-cancer markers for diagnosis, prognosis, and therapeutic decision-making by identifying cells with an embryonic or fetal phenotype, allowing for targeted treatment strategies to induce apoptosis or mature cells to arrest growth and metastasis, and can detect cancer stem cells resistant to chemotherapy.
Implementation Method 1
detection of differentially methylated regions (DMRs) of DNA associated with the EFT... determining the percent methylation of the CpG residues within the DMRs
Data Source
AI summary
The present invention relates to compositions and methods for the assay, diagnosis, prognosis or monitoring of the embryonic, fetal, and adult epigenetic states of a human genome. The disclosed methods are useful in monitoring the progress of in vitro and in vivo cellular reprogramming and the diagnosis, prognosis or monitoring of cancer in an individual. Specifically, the invention provides methods for the detection and interpretation of observed differential DNA methylation patterns and associated epigenetic modifications to core histones in determining the developmental status of human cells for the detection and characterization of cancer cells and determining optimum therapeutic modalities.


