Linear genome assembly from three dimensional genome structure

A method for genome assembly comprising:

• a) performing a DNA proximity ligation assay;
• b) generating a draft assembly of contigs and scaffolds from input sequencing reads obtained, at least in part, the DNA proximity ligation assay conducted on one or more samples;
• c) assembling larger sequences corresponding to one or more DNA molecules in the one or more samples by iteratively overlapping, ordering, orienting, and merging the contigs and scaffolds in the draft assembly, wherein a proper orientation of contigs and/or scaffolds is determined, at least in part, by 3D contact features, wherein the features in question are centromere-to-centromere interactions, telomere-to-telomere interactions and centromere-to-telomere interactions or a combination thereof;
• d) performing misjoin correction on the scaffolds, wherein the misjoin correction uses contact frequency between sequences in the scaffolds generated from a contact matrix to determine one or more misjoin;
• and
• e) generating one or more megascaffolds from the corrected scaffolds, wherein generating one or more megascaffolds comprises using a density graph to construct hemi-scaffolds from the corrected scaffolds and transforming the density graph into a confidence graph, the confidence graph constructs one or more megascaffolds from the hemi-scaffolds,
• the contact features are determined, at least in part, by data from the DNA proximity ligation assay.