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SCA-seq Multi-Omics Service: Accessibility, Methylation & 3D Genome

Achieve the ultimate resolution in epigenomic profiling with our SCA-seq Multi-Omics Service. By integrating NOMe-seq chemistry with Hi-C, we simultaneously map chromatin accessibility, DNA methylation, and 3D genome architecture on single DNA molecules. Ideal for dissecting complex regulatory mechanisms and heterogeneity in cancer and development. RUO.

  • Triple-Omics: Simultaneous Accessibility (GpC), Methylation (CpG), and Hi-C.
  • Single-Molecule Logic: Correlate epigenetic states directly with chromatin loops.
  • NOMe Principle: Uses GpC methyltransferase to "footprint" open chromatin.
  • Global Architecture: Retains compartment and TAD information unlike capture methods.
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3D illustration of SCA-seq mechanism showing GpC and CpG methylation on a DNA loop.

Overview: Resolving High-Order Epigenomic Interactions

In the rapidly evolving field of epigenetics, understanding how the genome folds is only half the story. To truly decode gene regulation, researchers need to know which regulatory elements are "open" (accessible), what their DNA methylation status is, and which distant genes they physically touch. Traditionally, this required three separate experiments—Hi-C, ATAC-seq, and Bisulfite Sequencing—forcing scientists to stitch together data from different cells and hope the correlations held true.

Our SCA-seq Multi-Omics Service (Spatial Chromatin Accessibility sequencing) shatters this limitation. By leveraging a unique "triple-omics" chemistry, SCA-seq captures 3D chromatin interactions, Chromatin Accessibility, and DNA Methylation simultaneously on the exact same DNA molecules.

Using a specialized GpC methyltransferase (M.CviPI) to "paint" open chromatin regions before capturing their 3D contacts, SCA-seq allows you to trace high-order regulatory hubs with unprecedented clarity. Whether you are studying complex diseases, developmental lineages, or cancer heterogeneity, this service delivers the ultimate multi-modal view of the genome from a single biological sample.

Service Snapshot

  • Triple-Omics: Structure, Accessibility, Methylation.
  • Resolution: Single-Molecule & Multi-way.
  • Method: GpC labeling + Proximity Ligation.
  • Sample Input: Low input compatible.

Why Choose SCA-seq for Multi-Omics?

True Multi-Omics on Single Molecules

The "averaging problem" plagues bulk genomics. SCA-seq solves this. Because the accessibility marker (GpC methylation) and the chromatin loop are recorded on the same sequenced DNA fragment (concatemer), you can definitively state: "This specific open enhancer is physically bound to this specific promoter."

Unbiased Genome Coverage

Unlike methods that rely solely on Tn5 transposase (which only captures open chromatin), SCA-seq utilizes restriction enzymes and GpC labeling. This means it captures the 3D structure of the entire genome—both the active, open compartments and the silent, heterochromatic regions.

Deciphering "Hybrid" Regulatory States

SCA-seq excels at identifying "hybrid concatemers"—single DNA molecules that contain both accessible (active) and inaccessible (silent) segments linked together. This capability allows for the dissection of complex regulatory logic, such as how a poised promoter might interact with a distal silencer.

Technical Comparison: SCA-seq vs. HiCAR vs. Methyl-Hi-C

Feature SCA-seq (Our Service) HiCAR Methyl-Hi-C
Data Layers 3 (Structure + Access + Meth) 2 (Structure + Access) 2 (Structure + Meth)
Accessibility Source GpC Methyltransferase Tn5 Transposase None
Methylation Source Endogenous CpG None (unless added) Endogenous CpG
3D Capture Proximity Ligation (Concatemers) Proximity Ligation Proximity Ligation
Resolution Single-Molecule / Multi-way Enhancer-Promoter Loop / TAD
Best For Maximum Data Density Low Input / V2G Imprinting / Methylome

SCA-seq Workflow: From Single Molecule to Triple Omics

Our SCA-seq workflow combines enzymatic labeling with high-throughput sequencing to encode three layers of information into one library.

  1. Nuclei Preparation: High-quality nuclei are isolated from fresh or frozen samples to ensure chromatin integrity.
  2. GpC Methylation Labeling: We treat the nuclei with the M.CviPI enzyme. This enzyme enters the nucleus and methylates cytosines in "GpC" contexts, but only where the chromatin is open and accessible.
  3. Chromatin Digestion & Ligation: The chromatin is digested with a restriction enzyme and re-ligated under dilute conditions to form "concatemers."
  4. Bisulfite Conversion: The DNA is treated with bisulfite, preserving both the Endogenous Methylation (CpG) and our Accessibility Footprint (GpC).
  5. Sequencing & Analysis: The library is sequenced. Bioinformatics pipelines separate GpC (accessibility) and CpG (methylation) signals while mapping 3D loops.

Step-by-step workflow diagram of the SCA-seq multi-omics service.

Sample Requirements (SCA-seq)

Sample Type Recommended Input Minimum Input Storage/Transport
Cultured Cells 1 Million cells 200,000 cells Fresh (On Ice) or Frozen Pellet (Dry Ice)
Tissue 50-100 mg 20 mg Fresh (On Ice) or Flash Frozen (Dry Ice)
Isolated Nuclei 1 Million nuclei 200,000 nuclei Frozen in Storage Buffer (Dry Ice)

*Note: FFPE samples are generally not recommended for SCA-seq due to DNA fragmentation. Please consult our team for challenging sample types.

Demo Results: Visualizing Triple-Omics Synergy

We provide advanced data visualization that bridges the gap between macro-scale genome architecture and micro-scale single-molecule interactions.

Composite genomic data view showing Hi-C heatmap and single-molecule concatemer tracks with accessibility and methylation dots.Integrated Triple-Omics View

Macro View (Left)

A standard 2D Contact Heatmap (Hi-C style) showing the overall domain structure (TADs) and loops at a specific locus. This highlights the general regulatory landscape.

Micro View (Right)

A "Single-Molecule Concatemer" track displaying individual DNA molecules. Connectivity, Accessibility (Purple Dots), and Methylation (Green Dots) are mapped on each line to identify "Hybrid Concatemers".

Case Study: Spatial Chromatin Accessibility and Epigenomic Markers

Deciphering how multiple epigenetic layers coordinate to regulate gene expression is a central challenge in biology. In a 2024 study published in eLife, researchers utilized SCA-seq to resolve these high-order interactions in human cells.

The study applied SCA-seq to capture multi-way chromatin interactions. By analyzing the resulting "concatemers" (long DNA molecules containing multiple ligated fragments), they could simultaneously read out the 3D connectivity, chromatin accessibility, and DNA methylation status of specific genomic loci.

The power of SCA-seq was demonstrated in the analysis of the chr7 promoter-enhancer region (Figure 4a). The data revealed individual DNA molecules that physically linked the gene promoter to distal enhancers. Crucially, the "footprint" data on these same molecules showed that the enhancer regions were highly accessible (rich in GpC methylation) and hypomethylated.

eLife Figure 4a visualization showing single-molecule concatemers with multi-omics markers.

SCA-seq successfully resolved the high-order spatial organization of the genome, providing a unified view of how accessibility and methylation patterns are spatially coordinated within the nucleus. (Source: Spatial chromatin accessibility sequencing resolves high-order spatial interactions of epigenomic markers, eLife, 2024.)

Frequently Asked Questions

References

  1. Spatial chromatin accessibility sequencing resolves high-order spatial interactions of epigenomic markers. eLife. 2024.
  2. HiCAR is a robust and sensitive method to analyze open-chromatin-anchored interactions with low-input cells. Molecular Cell. 2022.
  3. Identifying synergistic high-order 3D chromatin conformations using Pore-C. Nature Biotechnology. 2022.
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High-confidence 3D genomics services for chromatin interaction analysis and regulatory insight.

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