HiNT: a computational method for detecting copy number variations and translocations from Hi-C data

Wang, Su; Lee, Soohyun; Chu, Chong; Jain, Dhawal; Nelson, Geoff; Walsh, Jennifer; Alver, B.; Park, Peter J.

doi:10.1101/657080

Cited by 3 publications

(1 citation statement)

References 38 publications

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“…Copy number variations (CNVs) at a 50-kb resolution were calculated using HiNT software. 22 The sequencing coverage and quality statistics of each sample were summarized in Table S1.…”

Section: In Situ Hi-c and Hi-c Analysismentioning

confidence: 99%

Tumorigenic activation around HPV integrated sites in head and neck squamous cell carcinoma

Mima

Okabe

Hoshii

et al. 2023

Intl Journal of Cancer

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Human papillomavirus (HPV) is causally involved in the development of head and neck squamous cell carcinoma (HNSCC). The integration of HPV drives tumorigenesis through expression of oncogenic viral genes as well as genomic alterations in surrounding regions. To elucidate involvement of epigenetic dysregulation in tumorigenesis, we here performed integrated analyses of the epigenome, transcriptome and interactome using ChIP‐seq, RNA‐seq and Hi‐C and 4C‐seq for HPV(+) HNSCCs. We analyzed clinical HNSCC using The Cancer Genome Atlas data and found that genes neighboring HPV integration sites were significantly upregulated and were correlated with oncogenic phenotypes in HPV(+) HNSCCs. While we found four HPV integration sites in HPV(+) HNSCC cell line UPCI‐SCC‐090 through target enrichment sequencing, 4C‐seq revealed 0.5 to 40 Mb of HPV‐interacting regions (HPVIRs) where host genomic regions interacted with integrated HPV genomes. While 9% of the HPVIRs were amplified and activated epigenetically forming super‐enhancers, the remaining non‐amplified regions were found to show a significant increase in H3K27ac levels and an upregulation of genes associated with GO terms, for example, Signaling by WNT and Cell Cycle. Among those genes, ITPR3 was significantly upregulated, involving UPCI‐SCC‐090‐specific super‐enhancer formation around the ITPR3 promoter and in the 80‐kb‐downstream region. The knockdown of ITPR3 by siRNA or CRISPR deletions of the distant enhancer region led to a significant suppression of cell proliferation. The epigenetic activation of HPVIRs was also confirmed in other cell lines, UM‐SCC‐47 and UM‐SCC‐104. These data indicate that epigenetic activation in HPVIRs contributes, at least partially, to genesis of HPV(+) HNSCC.

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“…Copy number variations (CNVs) at a 50-kb resolution were calculated using HiNT software. 22 The sequencing coverage and quality statistics of each sample were summarized in Table S1.…”

Section: In Situ Hi-c and Hi-c Analysismentioning

confidence: 99%

Tumorigenic activation around HPV integrated sites in head and neck squamous cell carcinoma

Mima

Okabe

Hoshii

et al. 2023

Intl Journal of Cancer

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Genome reconstruction and haplotype phasing using chromosome conformation capture methodologies

Xu¹,

Dixon²

2019

Briefings in Functional Genomics

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Abstract Genomic analysis of individuals or organisms is predicated on the availability of high-quality reference and genotype information. With the rapidly dropping costs of high-throughput DNA sequencing, this is becoming readily available for diverse organisms and for increasingly large populations of individuals. Despite these advances, there are still aspects of genome sequencing that remain challenging for existing sequencing methods. This includes the generation of long-range contiguity during genome assembly, identification of structural variants in both germline and somatic tissues, the phasing of haplotypes in diploid organisms and the resolution of genome sequence for organisms derived from complex samples. These types of information are valuable for understanding the role of genome sequence and genetic variation on genome function, and numerous approaches have been developed to address them. Recently, chromosome conformation capture (3C) experiments, such as the Hi-C assay, have emerged as powerful tools to aid in these challenges for genome reconstruction. We will review the current use of Hi-C as a tool for aiding in genome sequencing, addressing the applications, strengths, limitations and potential future directions for the use of 3C data in genome analysis. We argue that unique features of Hi-C experiments make this data type a powerful tool to address challenges in genome sequencing, and that future integration of Hi-C data with alternative sequencing assays will facilitate the continuing revolution in genomic analysis and genome sequencing.

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HiNT: a computational method for detecting copy number variations and translocations from Hi-C data

Lee

Chu

et al. 2020

Genome Biol

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The three-dimensional conformation of a genome can be profiled using Hi-C, a technique that combines chromatin conformation capture with high-throughput sequencing. However, structural variations often yield features that can be mistaken for chromosomal interactions. Here, we describe a computational method HiNT (Hi-C for copy Number variation and Translocation detection), which detects copy number variations and interchromosomal translocations within Hi-C data with breakpoints at single base-pair resolution. We demonstrate that HiNT outperforms existing methods on both simulated and real data. We also show that Hi-C can supplement whole-genome sequencing in structure variant detection by locating breakpoints in repetitive regions.

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HiNT: a computational method for detecting copy number variations and translocations from Hi-C data

Cited by 3 publications

References 38 publications

Tumorigenic activation around HPV integrated sites in head and neck squamous cell carcinoma

Tumorigenic activation around HPV integrated sites in head and neck squamous cell carcinoma

Genome reconstruction and haplotype phasing using chromosome conformation capture methodologies

HiNT: a computational method for detecting copy number variations and translocations from Hi-C data

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