Contact genomics: scaffolding and phasing (meta)genomes using chromosome 3D physical signatures.
High-throughput DNA sequencing technologies are fuelling an accelerating trend to assemble de novo or resequence the genomes of numerous species as well as to complete unfinished assemblies. While current DNA sequencing technologies remain limited to reading stretches of a few hundreds or thousands of base pairs, experimental and computational methods are continuously improving with the goal of assembling entire genomes from large numbers of short DNA sequences. However, the algorithms that piece together DNA strands face important limitations due, notably, to the presence of repeated sequences or of multiple haplotypes within one genome, thus leaving many assemblies incomplete. Recently, the realization that the physical contacts experienced by a portion of a DNA molecule could be used as a robust and quantitative assay to determine its genomic position has led to the emerging field of contact genomics, which promises to revolutionize current genome assembly approaches by exploiting the flexible polymer properties of chromosomes. Here we review the current applications of contact genomics to genome scaffolding, haplotyping and metagenomic assembly, then outline the future developments we envision.
Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK. Electronic address: j.flot@ucl.ac.uk.
Jean-François
JF
Flot
Institut Pasteur, Department of Genomes and Genetics, Groupe Régulation Spatiale des Génomes, 75015 Paris, France; CNRS, UMR 3525, 75015 Paris, France. Electronic address: herve.marienelly@gmail.com.
Hervé
H
Marie-Nelly
Institut Pasteur, Department of Genomes and Genetics, Groupe Régulation Spatiale des Génomes, 75015 Paris, France; CNRS, UMR 3525, 75015 Paris, France. Electronic address: romain.koszul@pasteur.fr.
Romain
R
Koszul
D000818:Animals; D002875:Chromosomes / Q000502:physiology / Q000648:ultrastructure*; D016000:Cluster Analysis; D004843:Epistasis, Genetic; D053263:Gene Regulatory Networks; D023281:Genomics; D006239:Haplotypes; D006801:Humans; D054892:Metagenome; D017422:Sequence Analysis, DNA
3C; Contact genomics; Genome assembly; Haplotype phasing; Hi-C; Metagenomics; Scaffolding