Hi-C as a tool for precise detection and characterisation of chromosomal rearrangements and copy number variation in human tumours

Abstract

Chromosomal rearrangements occur constitutionally in the general population and somatically in the majority of cancers. Detection of balanced rearrangements, such as reciprocal translocations and inversions, is troublesome, which is particularly detrimental in oncology where rearrangements play diagnostic and prognostic roles. Here we describe the use of Hi-C as a tool for detection of both balanced and unbalanced chromosomal rearrangements in primary human tumour samples, with the potential to define chromosome breakpoints to bp resolution. In addition, we show copy number profiles can also be obtained from the same data, all at a significantly lower cost than standard sequencing approaches.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1253-8) contains supplementary material, which is available to authorized users.

Genetic diversity and relationship between domesticated rye and its wild relatives as revealed through genotyping‐by‐sequencing

“…If incomplete lineage sorting also extends to structural variants such as chromosomal inversions, we can expect to find chromosomal rearrangements to underlie both apparently interspecies fertility barriers and occasional intraspecific hybrid sterility as has been observed in rye (Stutz, ). The construction of interspecific linkage maps and the application of novel methods for physical genome mapping such as chromosome conformation capture sequencing (Harewood et al., ) or optical mapping (Lam et al., ) are promising avenues for unraveling the causes for partial reproductive isolation between rye taxa, which may also shed light on the genetic basis of differences in the key characters self‐compatibility and annual life cycle.…”

The Juicebox Assembly Tools module facilitatesde novoassembly of mammalian genomes with chromosome-length scaffolds for under $1000

“…When a chromosome is correctly assembled, sequences that are adjacent in the assembly are also in close physical proximity, leading to the appearance of a bright band of elevated contact frequency along the diagonal of the Hi-C heatmap. Conversely, when there are errors in a reference assembly, they are often visually obvious as anomalous patterns in the heatmap (Rao, Huntley et al 2014;Harewood et al 2017;Dudchenko et al 2017;Lapp et al 2017). Thus, in addition to its use as an input to automated assemblers, Hi-C can also facilitate the visual identification of errors in a genome assembly.…”

“…Examples of such errors can be found in the best available reference genomes for many species (Robert B. Norgren 2013;Shearer et al 2014;Tang et al 2014;Chen et al 2015;Davey et al 2016;Utsunomiya et al 2016;Schneider et al 2017;Korlach et al 2017). Consequently, inexpensive methods for identifying and correcting assembly errors are crucial for the generation of accurate assemblies (Salzberg and Yorke 2005;Phillippy, Schatz, and Pop 2008;Gnerre et al 2009;Tsai, Otto, and Berriman 2010;Salzberg et al 2012;Hunt et al 2013;Gurevich et al 2013;Bradnam et al 2013;Simão et al 2015;Fierst 2015;Muggli et al 2015;Yuan et al 2017;Harewood et al 2017). Of course, improved error correction procedures can also reduce the amount of input data required, and thereby the cost of genome assembly.…”

“…For instance, a translocation typically manifests as an extremely bright bowtie motif pointing horizontally or vertically, whose midpoint corresponds to two loci that are proximate in the genome but lie far apart in the assembly (Rao, Huntley et al 2014;Dudchenko et al 2017;Harewood et al 2017). By clicking-and-dragging, a user can highlight the desired genomic interval, and -with a single click -move the interval to the desired position in the assembly (see Fig.…”

Iteratively improving Hi-C experiments one step at a time

“…This is the case with approaches such as Capture-C [18], Hi-ChIP [19], and others. Further, it has recently become clear that Hi-C is a very useful tool not only for measuring 3D genome folding, but also for de novo whole genome sequence assembly [20][21][22] and translocation detection [23]. As basic researchers from many fields, commercial ventures (such as Phase Genomics and Dovetail Genomics), and clinical researchers adopt Hi-C based techniques, it is more important than ever to optimize the methodological details of the Hi-C protocol and understand how they affect the resulting data and interpretation.…”