This study demonstrates the use of genome-wide chromatin interaction datasets, such as those generated by Hi-C, to improve the contiguity of de novo genome assemblies. The authors developed an algorithm called LACHESIS (ligating adjacent chromatin enables scaffolding in situ) to exploit long-range information from Hi-C data for assigning, ordering, and orienting genomic sequences to chromosomes. The method was tested on human, mouse, and Drosophila genomes, achieving high accuracy in clustering scaffolds into chromosome groups (98% accuracy for human) and ordering and orienting scaffolds within these groups (99% accuracy for human). The approach also showed promise in validating chromosomal translocations in cancer genomes. The study highlights the potential of Hi-C data to enhance the quality of de novo genome assemblies, bringing them closer to the standards set by the Human Genome Project.This study demonstrates the use of genome-wide chromatin interaction datasets, such as those generated by Hi-C, to improve the contiguity of de novo genome assemblies. The authors developed an algorithm called LACHESIS (ligating adjacent chromatin enables scaffolding in situ) to exploit long-range information from Hi-C data for assigning, ordering, and orienting genomic sequences to chromosomes. The method was tested on human, mouse, and Drosophila genomes, achieving high accuracy in clustering scaffolds into chromosome groups (98% accuracy for human) and ordering and orienting scaffolds within these groups (99% accuracy for human). The approach also showed promise in validating chromosomal translocations in cancer genomes. The study highlights the potential of Hi-C data to enhance the quality of de novo genome assemblies, bringing them closer to the standards set by the Human Genome Project.