Long Read Sequencing for Chromatin Conformation

The structure of eukaryotic chromosome folding has been continuously analyzed in depth by the chromosome conformation capture (3C) family of techniques. However, traditionally used short-read 3C methods limit the number of contacts that can be analyzed per read. Combining 3C with long-read sequencing can provide long-distance contact information and reveal higher-order structures. CD Genomics is a leading global life sciences company, and we continue to expand our solutions and improve our available resources to help scientists accelerate their basic research. Based on our advanced PacBio SMRT sequencing and ONT Nanopore sequencing, and years of sequencing experience, we are committed to providing the best solutions to analyze the three-dimensional conformation of eukaryotic chromatin to meet the project needs of our customers worldwide.

Introduction to Chromatin Conformation

Linear chromatin undergoes multiple folding and condensation into the nucleus of eukaryotic cells, and chromatin structural domains and loops are important elements of chromatin structure and dynamics. The three-dimensional conformation of chromatin affects gene expression during development, evolution, and disease. So that chromatin can interact locally or remotely in space to regulate gene transcription. Chromatin folded into a circular conformation can be studied with the help of the chromosome conformation capture (3C) technique. Chromosome interaction mapping (Hi-C) is a modification of the 3C method that identifies long-range chromosomal interactions in an unbiased manner without a priori target site selection. However, this method has limited ability to construct small overlapping clusters in fragmented short-read long assemblies. Long-read sequencing technology can produce tens of kilobase-sized reads that can theoretically assemble complete mammalian chromosomes. Scientists have successfully combined long-read single-molecule sequencing, high-fidelity short-read long sequencing, optical mapping, and Hi-C-based chromatin interaction mapping to visualize the reference genome of the domesticated goat (C. hircus).

Fig. 1. The 3D organization of chromatin. (Boltsis et al., 2021)

Solutions Offering at CD Genomics

CD Genomics offers complete long-read sequencing solutions for studying chromatin conformation, including genome-wide assessment of combinatorial chromatin interactions, disease rearrangement reconstruction, and de novo genomics, etc. We ensure that you get a panoramic view of chromatin interactions, which can provide critical information on the impact of chromatin structure on transcriptional regulation. Our end-to-end workflow also ensures a smooth transition from sample preparation to comprehensive analysis for a range of sample types including whole blood, animal tissues, plant tissues, and microbes.

In addition to studying chromatin structure, long-read data from the 3C analysis workflow enables the construction of genome assemblies and correction of genomes. These data can be used to target overlapping clusters to produce highly contiguous scaffold assemblies. We can combine long-read sequencing technology with Hi-C to differentiate and assemble the genomes of fungal, bacterial, and archaeal species, and are able to efficiently and qualitatively characterize and assemble the genomes of multiple single species from microbial communities. In addition, these data allow for the resolution of structural variants (SVs) across megabase sizes and understanding their association with chromatin conformation.

Our long-read sequencing solution for chromatin conformation helps you obtain the following information:

• Enhanced, multiplexed chromatin interaction data
• Epigenetic modifications
• Whole genome sequence data for downstream assembly
• SV detection and resolution, including highly complex, million-base spanning variants

Advantages of Long Read Sequencing for Chromatin Conformation

• In-depth multiplexed chromatin interaction data
  While short-read sequencing limits contact analysis to pairwise interactions, long-read sequencing reveals multidirectional chromatin interactions. This comprehensive interaction data paints a detailed picture of the chromatin landscape, providing insights that can revolutionize our understanding of gene regulation and genome structure.
• Amplification bypassing real data
  Typical chromatin conformation methods (e.g. Hi-C) rely on amplification steps that can introduce bias. Our solution does not require amplification and ensures a direct, true representation of chromatin structure and its modifications.
• Enhancing genome assembly with remote data
  In addition to chromatin conformation, long read sequencing obtained through our approach can significantly enhance genome assembly. Whether constructing genomes or resolving structural variation across megabase sizes, the depth and breadth of data obtained through long-read sequencing are unparalleled.
• A holistic view of gene regulation
  Long read sequencing of chromatin conformation provides not only structural data but also insights into the regulation of gene expression. By capturing both structural and epigenetic data, CD Genomics' advanced technology provides a unified view of the multiple layers of control that determine gene expression.

With its unparalleled expertise and cutting-edge technology, CD Genomics is a trusted partner in the genomics community, constantly pushing the boundaries of what is possible with 3C technologies. Our goal is to unravel the myriad mysteries of chromatin 3D structure and its impact on health and disease. If you have any questions, please feel free to contact us. We look forward to working with you on projects of interest.

Related Services

PacBio SMRT Sequencing
Oxford Nanopore Sequencing
Human Genome Structural Variation Detection
Animal/Plant Whole Genome De Novo Sequencing