Center for Epigenomics
Fee-for-service Assays

To initiate a new project, please contact the Center for Epigenomics at epigenome@health.ucsd.edu. Samples can include cryopreserved cells, frozen tissue, frozen cross-linked cells or nuclei pellets. For details on sample preparation please contact us. The service includes nuclei and library preparation, including all reagents and labor costs associated with library preparation as well as shallow quality check sequencing and deep sequencing basic data processing and quality analysis are also included in this portion of the cost.

SINGLE-CELL ASSAYS:

Single-cell multiomics: Multiome, Chromium Single-Cell Multiome ATAC + Gene Expression (10x Genomics) simultaneously profiles chromatin accessibility and the transcriptome in the same cell.

Single-cell ATAC-seq and single-cell RNA-seq (10x Genomics) can be used to define and characterize cellular lineages and diversity in mixed populations with unprecedented resolution. The former aids the molecular interpretation of disease and phenotype traits associated with genetic variants. The latter identifies the cell types that change during development, disease, and drug treatment.

Single-cell Paired-Tag: is an innovative assay that allows correlating core histone modifications with its transcriptional output at a single-cell resolution. It yields a comprehensive profiling of chromatin states and gene expression allowing for an unprecedented depth of the regulation of the cell states during development and disease as well as upon a stimulation with drugs and compounds.

Single-nucleus Methyl-3C sequencing (snm3C-seq) delineates the heterogeneous relationship between chromatin architecture and DNA methylation status in mixed cellular populations. This is achieved by profiling both DNA methylation and 3D chromatin contacts from the same cell, giving cell type/state resolved epigenome and genome organization information from complex tissues. DNA methylation profiles are highly cell type and context specific and effective in resolving cell types by Single-Cell clustering methods. DNA methylation is a dynamic epigenetic modification that plays roles in development and disease. Regulatory regions, such as promoters and enhancers, are generally hypomethylated when active and mark the binding of regulatory proteins that influence gene expression. In the same cell, this assay additionally provides chromatin contact information to reconstruct the 3D genome organization. The organization of the genome informs gene regulatory programs such as close proximity of distal regulatory elements to their target genes, even when far away in the linear genome. Coupling both modalities in the same cell allows for higher resolution Single-Cell clustering and more accurate cell type identification.

NUCLEI PREPARATION:

The success of single nucleus assay is highly dependent on optimized nuclei preparation conditions, therefore we select from a panel of sample/tissue dissociation, and primary and secondary sample purification and nuclei enrichment methods to isolate the highest quality material and maximize data quality and minimize the data noise i.e. minimizing the ambient RNA signal.

SPATIAL GENOMICS AND EPIGENOMICS:

Visium HD: is a probe-based high-resolution spatial biology technique that enables single-cell scale gene expression analysis of whole transcriptomes from FFPE samples.The Visium HD assay allow to identify rare cellular phenotypes, elucidate cell-cell interactions, and build resources like tissue atlases at an unprecedented resolution.

MERFISH: The Center provides unparalleled access to transformative spatial genomics techniques for deep insights into gene expression and cellular function. Using custom-built MERFISH imaging systems, researchers can image transcripts of 300, 500, and up to 3,000 genes with remarkable precision, quantifying their copy numbers and mapping their 3D localization. The Center's cutting-edge technology is complemented by hands-on support and guidance, ensuring seamless integration into research workflows.

MERSCOPE: The Center's MERSCOPE instruments enable high-resolution spatial mapping of up to 960 RNA targets with subcellular precision (≤100nm). Built-in machine learning algorithms enhance on-instrument cell segmentation by integrating nuclei staining, mRNA abundance, and cell boundary staining. The Center offers both custom and predesigned panels compatible with frozen and FFPE samples. This flexibility makes it ideal for a wide range of research applications.

Xenium: The Center’s Xenium Analyzer from 10X Genomics enables high-throughput RNA FISH for precise spatial mapping of up to 480 custom or 5,000 predesigned RNA targets at subcellular resolution (~0.2 microns/pixel). Each instrument runs two slides, covering a total area of 5.76 cm², ideal for large-scale studies. Advanced machine learning combines nuclei staining, RNA/protein abundance, and cell boundary staining for accurate cell segmentation. Additionally, H&E or IF staining can be performed on the same slide post-run, enabling the overlay of pathological analysis with gene expression data.

Super-resolution chromatin tracing: The Center offers researchers access to custom-built MERFISH imaging systems, providing cutting-edge technology to visualize chromatin architecture using massively-multiplexed and multi-modal technology. This advanced multiplexed FISH technique reveals higher-order chromatin structures with remarkable consistency compared to Hi-C data. With multiple imaging systems, the Center enables the visualization of individual chromatin 3D architecture at resolutions ranging from 2kb ultra-high resolution to genome-scale. This is achieved through sequential, multiplexed, high-throughput hybridization and imaging of oligopaint probes, delivering unprecedented insights into chromatin organization in cultured cells and human complex tissues.

BULK ASSAYS:

ATAC-seq (assay for transposase-accessible chromatin using sequencing) identifies genomic regulatory elements with an engineered transposase that inserts sequencing adapters into accessible genomic sites. It allows the quantification of chromatin rearrangements during healthy and pathological biological processes, or upon exposure to stimulants like drugs and compounds. When combined with genotyping data it allows to identify and annotate functional variants driving the chromatin accessibility changes.

CUT&TAG (cleavage under targets & tagmentation) quantifies the proteins binding to the genome. CUT&RUN and CUT&TAG improve on ChIP-seq by eliminating steps that may alter the DNA-binding behavior of proteins. These emerging methods offer streamlined workflows, require fewer cells, and often yield data with higher signal-to-noise ratios.

Hi-C captures the 3D interactions between pairs of functionally linked genomic loci. Unlike previous chromatin conformation capture methods, this technique can assay the 3D structure of chromatin across an entire genome.