Phase Genomics´ proximity ligation (Hi-C) chemistry and computational tools enable you to generate direct, quantitative evidence of the spatial relationships between DNA sequences in vivo. This “ultra long-range” information adds another dimension to shotgun sequence data. It enables deeper insights into the architecture, variation, function and complexity of genomes, epigenomes, microbiomes and metagenomes.
How Proximity Ligation (Hi-C) works: Chimeric junctions between adjacent sequences encode quantitative, long-range information
DNA is crosslinked in vivo to fix all of the DNA contained in the cell. Crosslinking “traps” sequences that are in close proximity to one another, across the entire genome and between different chromosomes. In microbes, interactions between genomic DNA and mobile genetic elements (e.g. plasmids and transposons) are also captured. Crosslinked DNA is subsequently fragmented with endonucleases. Fragmented loci are biotinylated and proximity ligated, creating chimeric junctions between adjacent sequences. Biotinylated junctions are purified and subjected to deep, paired-end sequencing.
The information contained in the chimeric junctions is not limited to sequence (position in the linear genome), but can be decoded to reveal the physical origin of each junction partner in the three-dimensional structure of the DNA. Proximity ligation reads are mapped against a draft assembly or shotgun data to improve the quality and reliability of complex genomes and metagenomes. This in turn, enables improved insights in many areas of biology and medicine:
Human Genomics and Epigenomics: Assemble fully phased de novo genomes, detect genetic and epigenetic variation, characterize translocations, copy number variation and TADs, analyze genome and chromatin architecture, study cancer, advance precision genomics.
Animal, Plant, and Fungal Genomics: Construct high-quality, chromosome-scale reference genomes, resolve haplotypes and polyploidy, compare and study gene structure, function and interactions, understand biology and evolution to conserve and protect biodiversity.
Metagenomics and Microbiology: Deconvolute complex metagenomic samples, discover new species, strains and genes, attribute mobile genetic elements to their hosts, study the human microbiome, infectious disease, antibiotic resistance and gene function.