Chicdiff: a computational pipeline for detecting differential chromosomal interactions in Capture Hi-C data

Cairns, Jonathan; Orchard, William R.; Malysheva, Valeriya; Spivakov, Mikhail

doi:10.1101/526269

Cited by 3 publications

(3 citation statements)

References 13 publications

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“…Chicdiff (Cairns et al, 2019) was used to detect differential promoter interactions between SCC1-AID control (Aux-) and depleted (Aux+) samples, and between CTCF-AID control (Aux-) and depleted (Aux+) samples. Chicdiff uses DESeq2 (Love et al, 2014) differential interaction calling with custom feature selection, normalisation and multiple testing correction procedures.…”

Section: Differential Pchi-c Interaction Callingmentioning

confidence: 99%

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Cohesin-dependent and independent mechanisms support chromosomal contacts between promoters and enhancers

Thiecke

Wutz

Muhar

et al. 2020

Preprint

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It is currently assumed that 3D chromosomal organisation plays a central role in transcriptional control. However, recent evidence shows that steady-state transcription of only a minority of genes is affected by depletion of architectural proteins such as cohesin and CTCF. Here, we have used Capture Hi-C to interrogate the dynamics of chromosomal contacts of all human gene promoters upon rapid architectural protein degradation. We show that promoter contacts lost in these conditions tend to be long-range, with at least one interaction partner localising in the vicinity of topologically associated domain (TAD) boundaries. In contrast, many shorter-range chromosomal contacts, particularly those that connect active promoters with each other and with active enhancers remain unaffected by cohesin and CTCF depletion. We demonstrate that the effects of cohesin depletion on nascent transcription can be explained by changes in the connectivity of their enhancers. Jointly, these results provide a mechanistic explanation to the limited, but consistent effects of cohesin and CTCF on steady-state transcription and point towards the existence of alternative enhancer-promoter pairing mechanisms that are independent of these proteins.

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Section: Differential Pchi-c Interaction Callingmentioning

confidence: 99%

“…of our recently developed differential calling pipeline for PCHi-C data, Chicdiff (Cairns et al, 2019). Integrating Chicdiff and clustering results, we defined 36,174 lost; 12,978 maintained; and 2,484 gained interactions upon cohesin depletion (Figs 2A-C and S1C).…”

Section: Introductionmentioning

confidence: 99%

Cohesin-dependent and independent mechanisms support chromosomal contacts between promoters and enhancers

Thiecke

Wutz

Muhar

et al. 2020

Preprint

Self Cite

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“…All baitto-bait interactions were discarded. Chicdiff package 42 (v.0.6) was used to compare PCHi-C data from Vehicle and Decitabine tumours and the difference in the mean asinh-transformed CHiCAGO scores between conditions above 1 was used to prioritise the potential differential promoter-anchored interactions. Only interactions that have CHiCAGO score of more than 5 in at least 2 replicates were included for downstream analysis.…”

Section: Pchi-c Analysesmentioning

confidence: 99%

Epigenetic therapy targets the 3D epigenome in endocrine-resistant breast cancer

Achinger-Kawecka

Stirzaker

Chia

et al. 2021

Preprint

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Three-dimensional (3D) epigenome remodelling is emerging as an important mechanism of gene deregulation in cancer. However, its potential as a target to overcome cancer therapy resistance remains largely unaddressed. Here we show that treatment of endocrine-resistant estrogen receptor positive (ER+) breast cancer with an FDA-approved epigenetic therapy Decitabine (5-Aza-mC), results in genome-wide DNA hypomethylation and suppression of tumour growth in preclinical metastatic ER+ breast tumour xenograft models. Systematic integration of matched chromatin conformation capture (Hi-C), Promoter Capture Hi-C, RNA-seq and ER ChIP-seq data revealed widespread effects on epigenome deregulation, including de-compaction of higher order chromatin structure and loss of topologically associating domains (TAD) boundary insulation. Key enhancer ER binding sites were demethylated and re-activated after Decitabine treatment, resulting in new ER mediated enhancer-promoter interactions and concordant activation of tumour suppressive gene pathways. Importantly, we show that the activated ER target genes were also predictive of good outcome in multiple ER+ breast cancer clinical cohorts. Together our study reveals a previously undescribed mechanism of Decitabine in re-wiring DNA methylation-dependent 3D genome architecture resulting in suppression of tumour growth, and highlights the potential of epigenetic therapy in targeting ER+ endocrine-resistant breast cancer.

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Computational Processing and Quality Control of Hi-C, Capture Hi-C and Capture-C Data

Hansen

Gargano

Hecht

et al. 2019

Genes

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Hi-C, capture Hi-C (CHC) and Capture-C have contributed greatly to our present understanding of the three-dimensional organization of genomes in the context of transcriptional regulation by characterizing the roles of topological associated domains, enhancer promoter loops and other three-dimensional genomic interactions. The analysis is based on counts of chimeric read pairs that map to interacting regions of the genome. However, the processing and quality control presents a number of unique challenges. We review here the experimental and computational foundations and explain how the characteristics of restriction digests, sonication fragments and read pairs can be exploited to distinguish technical artefacts from valid read pairs originating from true chromatin interactions.

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Chicdiff: a computational pipeline for detecting differential chromosomal interactions in Capture Hi-C data

Cited by 3 publications

References 13 publications

Cohesin-dependent and independent mechanisms support chromosomal contacts between promoters and enhancers

Cohesin-dependent and independent mechanisms support chromosomal contacts between promoters and enhancers

Epigenetic therapy targets the 3D epigenome in endocrine-resistant breast cancer

Computational Processing and Quality Control of Hi-C, Capture Hi-C and Capture-C Data

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