Chromosome-Scale Scaffolding of de novo Genome Assemblies Using Hi-C

Genome sequencing is cheaper than ever before.  This makes it relatively easy to sequence genomic DNA from any plant or animal species and create a de novo genome assembly.  However, assemblies made from next-generation sequencing reads are highly fragmented, making post-genomic analysis very difficult.  To tackle this problem, we have developed Lachesis, a method that uses the long-range genomic information provided by a molecular technique called Hi-C.  Originally designed to study the 3D structure of genomes, Hi-C connects DNA fragments with their spacially adjacent partners within a cell.  The strong enrichment in Hi-C signal between genetically neighboring loci allows the scaffolding of entire chromosomes from fragmented draft assemblies.  Lachesis is the first tool that uses only short reads to create de novo assemblies of large genomes with chromosome-scale scaffolding.

We have also developed MetaPhase, a method that uses Hi-C to deconvolute individual genomes from within mixed metagenomic samples.  Since any locus pairs that interact by Hi-C must have originated within the same cell prior to lysis, this signal can be used to cluster sequence contigs based on species of origin.  MetaPhase can simultaneously deconvolute individual genomes from a microbiome sample and create high-quality genome assemblies of these species.  The creation of high-quality genomes from both eukaryotic and prokaryotic members of mixed microbial populations allows the discovery of novel unculturable species, relieving a major bottleneck in metagenomics.