Targeted Methylation Probe Panels for Cancer-Specific CpG Detection
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Solution Overview
Problem
Current DNA methylation profiling methods, such as whole genome bisulfate sequencing (WGBS), are not cost-effective for cancer diagnosis due to low differentially methylated regions and high sequencing costs, and face challenges in identifying differentially methylated regions accurately, especially with small control groups and varying methylation statuses.
Innovation Solution
A targeted methylation probe panel is developed for hybridization capture, comprising oligonucleotide-containing probes complementary to cancer-specific genomic regions with differentially methylated CpG sites, allowing for enriched sequencing of these regions using cell-free DNA (cfDNA) to detect cancer-specific methylation patterns.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If whole genome bisulfate sequencing (WGBS) is used for DNA methylation profiling, then comprehensive methylation coverage is achieved, but sequencing costs increase and sequencing depth in specific regions is insufficient
Solution Approach 1:
The patent extracts and focuses sequencing resources on only the most differentially methylated regions (DMRs) that are highly specific to cancer types, rather than sequencing the entire genome. By identifying and targeting approximately 100-1000 key DMRs per cancer type, the method achieves accurate cancer detection while dramatically reducing sequencing costs and increasing depth of coverage in relevant regions.
Solution Approach 2:
The patent applies local quality by concentrating sequencing depth and resources on specific genomic regions with high cancer-specific methylation signals rather than distributing resources uniformly across the genome. This targeted approach ensures high measurement precision in critical regions while minimizing overall sequencing costs.
2Measurement precision
If whole genome bisulfate sequencing (WGBS) is used for DNA methylation profiling, then comprehensive methylation coverage is achieved, but sequencing depth in specific regions is insufficient
Solution Approach 1:
The patent extracts and focuses sequencing resources on only the most differentially methylated regions (DMRs) that are highly specific to cancer types, rather than sequencing the entire genome. By identifying and targeting approximately 100-1000 key DMRs per cancer type, the method achieves accurate cancer detection while dramatically reducing sequencing costs and increasing depth of coverage in relevant regions.
3Productivity
If a small control group is used for identifying differentially methylated regions, then study cost and time are reduced, but identification accuracy of differentially methylated regions decreases
Solution Approach 1:
The patent performs preliminary action by pre-identifying and curating panels of cancer-specific differentially methylated regions using large reference datasets before actual diagnosis. This pre-characterization of DMRs with known cancer specificity allows small diagnostic cohorts to achieve high accuracy without requiring large control groups during the actual testing phase.
Solution Approach 2:
The patent uses large reference datasets to create a template or copy of known cancer-specific methylation patterns, which can then be applied to diagnose cancer in small patient cohorts. The pre-established DMR panels serve as a reference framework that enables accurate cancer detection even when the diagnostic control group is small.
4Productivity
If targeted genomic region panel is used instead of whole genome sequencing, then sequencing depth of target regions is increased, but genome coverage is reduced
Solution Approach 1:
The patent extracts and focuses sequencing resources on only the most differentially methylated regions (DMRs) that are highly specific to cancer types, rather than sequencing the entire genome. By identifying and targeting approximately 100-1000 key DMRs per cancer type, the method achieves accurate cancer detection while dramatically reducing sequencing costs and increasing depth of coverage in relevant regions.
Solution Approach 2:
The patent applies local quality by concentrating sequencing depth and resources on specific genomic regions with high cancer-specific methylation signals rather than distributing resources uniformly across the genome. This targeted approach ensures high measurement precision in critical regions while minimizing overall sequencing costs.
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 probe panel enhances cancer detection by increasing sequencing depth in relevant genomic regions, providing a cost-effective and non-invasive method for early cancer detection with high sensitivity and specificity across various cancer types.
Implementation Method 1
A targeted methylation probe panel is developed for hybridization capture, comprising oligonucleotide-containing probes complementary to cancer-specific genomic regions
Data Source
AI summary
The present description provides a cancer assay panel for targeted detection of cancer-specific methylation patterns. Further provided herein are methods of designing, making, and using the cancer assay panel for the diagnosis of cancer.