Simultaneous Analysis of Large Genomic Structural Variations and Their Epigenetic Profile
This innovative technology enables simultaneous quantification of DNA repeat sequences, large deletions, insertion, inversion and translocations, together with CpG methylation and hydromethylation patterns in individual molecules. By leveraging state-of-the-art optical mapping and fluorescence-based methylation detection, this method provides unprecedented precision in diagnosing diseases like facioscapulohumeral muscular dystrophy (FSHD) and cancers.
Unmet Need
Current technologies for analyzing DNA repeat regions and their methylation status suffer from limitations in resolution, sensitivity, and scalability. Next-generation sequencing and PCR-based methods often fail to address the complexity of repetitive regions and epigenetic modifications, leaving critical gaps in diagnostic capabilities for diseases influenced by genetic and epigenetic interactions.
Our Solution
This patented method combines optical genome mapping with advanced enzymatic labeling to deliver high-resolution, single-molecule analysis of DNA repeats and methylation status. The technology provides quantitative and qualitative data in a high-throughput, automated format, enabling comprehensive diagnostics for complex diseases.
Unique Advantages
• Simultaneous Analysis: Measures both DNA repeat number and methylation status in one assay.
• High Resolution: Offers single-molecule and single-repeat resolution.
• Versatility: Applicable to a wide range of repeat-related diseases and methylation-sensitive disorders.
• High Throughput: Integrates seamlessly with automated platforms like nanochannel-based optical mapping.
• Broad Applicability: Capable of mapping large genomic regions inaccessible to conventional methods.
Potential Applications
• Clinical Diagnostics: Precise detection and differentiation of genetic disorders (e.g., FSHD1, FSHD2, Huntington’s disease).
• Cancer Epigenetics: Profiling methylation variations in cancer diagnostics and progression monitoring.
• Genomic Research: High-resolution studies of repetitive DNA regions and epigenetic landscapes.
• Pharmacogenomics: Developing personalized treatment strategies based on epigenetic profiles.
• Biotechnology: Integration into advanced genomic analysis tools for research and development.
• Agtech: Plant genomes are prone to repetitive elements that are difficult to characterize
Status
• Genetic/epigenetic profiling of tumor matched pairs for clinical patient management-Kidney Cancer
• FSHD Diagnosis
References:
1. NAR Genomics and Bioinformatics 7 (1), lqae190
2. Genome research 29 (4), 646-656
Overall Summary
This technology stands out due to its ability to simultaneously analyze repeat DNA sequences and methylation patterns with high sensitivity, specificity, and throughput. It addresses significant gaps in current genomic and epigenetic tools, offering a powerful solution for diagnostics and research in challenging areas of the genome.
Copy Number Analysis (A) Model: FSHD BAC system with D4Z4 repeats, upstream DNA, and cloning vector. (B) Coverage: Box plots show normalized read coverage for repeat and nonrepetitive regions. (C) Labeling: Labeled DNA aligns with reference map. (D) Assembly: 627 molecules form a consensus map; nonrepetitive regions highlighted. (E) ROM Profiles: Repeat units detected in nonmethylated (green) and partially methylated (blue) samples.