FAN-C: A Feature-rich Framework for the Analysis and Visualisation of C data

Kruse, Kai; Hug, Clemens; Vaquerizas, Juan M.

doi:10.1101/2020.02.03.932517

Cited by 14 publications

(24 citation statements)

References 68 publications

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“…Hi-C data was analysed using (Kruse et al, 2020). Paired-end reads were scanned to identify ligation junctions, split at ligation junctions if any were present, and then aligned independently to the dm6 genome using BWA-MEM (version 0.7.17-r1188) (Li and Durbin, 2009).…”

Section: Competing Interestsmentioning

confidence: 99%

“…Aggregate compartment, domain, and loop plots were created using FAN-C. Compartments were identified using the first eigenvector of the correlation matrix of the normalised Hi-C data, using GC content to orient the eigenvector. The compartment eigenvector for the 3-4 hpf Hi-C data from Hug et al 2017 was used as the reference for the aggregate compartment plots ("saddle plots") (Flyamer et al, 2017;Gassler et al, 2017;Imakaev et al, 2012;Kruse et al, 2020). Domain aggregates were also created using the domains identified in the hpf Hi-C data.…”

Section: Competing Interestsmentioning

confidence: 99%

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Independence of 3D chromatin conformation and gene regulation during Drosophila dorsoventral patterning

Ing-Simmons

Vaid

Mannervik

et al. 2020

Preprint

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ABSTRACTThe relationship between the 3D organisation of chromatin inside the nucleus and the regulation of gene expression remains unclear. While disruption of domains and domain boundaries can lead to mis-expression of developmental genes, acute depletion of key regulators of genome organisation, such as CTCF and cohesin, and major reorganisation of genomic regions have relatively small effects on gene expression. Therefore, it is unclear whether changes in gene expression and chromatin state drive chromatin reorganisation, or whether changes in chromatin organisation facilitate cell type-specific activation of genes and their regulatory elements. Here, using the Drosophila melanogaster dorsoventral patterning system as a model, we demonstrate the independence of 3D chromatin organisation and developmental gene regulation. We define tissue-specific enhancers and link them to expression patterns at the single-cell level using single cell RNA-seq. Surprisingly, despite tissue-specific differences in chromatin state and gene expression, 3D chromatin organisation is maintained across tissues. Our results provide strong evidence that tissue-specific chromatin conformation is not required for tissue-specific gene expression, but rather acts as an architectural framework to facilitate proper gene regulation during development.

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Section: Competing Interestsmentioning

confidence: 99%

Section: Competing Interestsmentioning

confidence: 99%

Independence of 3D chromatin conformation and gene regulation during Drosophila dorsoventral patterning

Ing-Simmons

Vaid

Mannervik

et al. 2020

Preprint

Self Cite

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“…Consistent with these results, we find that regions of the genome which consistently form more contacts in normalized Hi-C are enriched for heterochromatin marks. We have found the bias in raw GAM datasets to be uniformly lower than that found in raw Hi-C, yet both methods have their own specific biases and improved normalisation algorithms have the potential to bridge the divergences between the two methods Chandradoss et al, 2020;Kruse et al, 2020;Liu and Wang, 2019).…”

Section: Discussionmentioning

confidence: 89%

Multiplex-GAM: genome-wide identification of chromatin contacts yields insights not captured by Hi-C

Beagrie

Thieme

Annunziatella

et al. 2020

Preprint

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Summary (Abstract)Technologies for measuring 3D genome topology are increasingly important for studying mechanisms of gene regulation, for genome assembly and for mapping of genome rearrangements. Hi-C and other ligation-based methods have become routine but have specific biases. Here, we develop multiplex-GAM, a faster and more affordable version of Genome Architecture Mapping (GAM), a ligation-free technique to map chromatin contacts genomewide. We perform a detailed comparison of contacts obtained by multiplex-GAM and Hi-C using mouse embryonic stem (mES) cells. We find that both methods detect similar topologically associating domains (TADs). However, when examining the strongest contacts detected by either method, we find that only one third of these are shared. The strongest contacts specifically found in GAM often involve “active” regions, including many transcribed genes and super-enhancers, whereas in Hi-C they more often contain “inactive” regions. Our work shows that active genomic regions are involved in extensive complex contacts that currently go under-estimated in genome-wide ligation-based approaches, and highlights the need for orthogonal advances in genome-wide contact mapping technologies.

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“…The resulting filtered pairs file was converted to a tsv file that was used as input for Juicer Tools Pre 69 , which generated multiresolution hic files. HiC matrices at 10 and 500 Kb resolution, normalized with the Knight-Ruiz (KR) method 70 , were extracted for downstream analysis using the FAN-C toolkit 71 . Visualization of normalized HiC matrices and other values described below, such as insulation scores, TAD boundaries, aggregate TAD and loop analysis, Pearson’s correlation matrices and eigenvectors, were calculated and visualized using FAN-C.…”

Section: Methodsmentioning

confidence: 99%

CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression

Franke

Calle‐Mustienes

Neto

et al. 2020

Preprint

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CTCF is an 11-zinc-finger DNA-binding protein that acts as a transcriptional repressor and insulator as well as an architectural protein required for 3D genome folding1–5. CTCF mediates long-range chromatin looping and is enriched at the boundaries of topologically associating domains, which are sub-megabase chromatin structures that are believed to facilitate enhancer-promoter interactions within regulatory landscapes 6–12. Although CTCF is essential for cycling cells and developing embryos13,14, its in vitro removal has only modest effects over gene expression5,15, challenging the concept that CTCF-mediated chromatin interactions and topologically associated domains are a fundamental requirement for gene regulation16–18. Here we link the loss of chromatin structure and gene regulation in an in vivo model and during animal development. We generated a ctcf knockout mutant in zebrafish that allows us to monitor the effect of CTCF loss of function during embryo patterning and organogenesis. CTCF absence leads to loss of chromatin structure in zebrafish embryos and affects the expression of thousands of genes, including many developmental genes. In addition, chromatin accessibility, both at CTCF binding sites and cis-regulatory elements, is severely compromised in ctcf mutants. Probing chromatin interactions from developmental genes at high resolution, we further demonstrate that promoters fail to fully establish long-range contacts with their associated regulatory landscapes, leading to altered gene expression patterns and disruption of developmental programs. Our results demonstrate that CTCF and topologically associating domains are essential to regulate gene expression during embryonic development, providing the structural basis for the establishment of developmental gene regulatory landscapes.

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FAN-C: A Feature-rich Framework for the Analysis and Visualisation of C data

Cited by 14 publications

References 68 publications

Independence of 3D chromatin conformation and gene regulation during Drosophila dorsoventral patterning

Independence of 3D chromatin conformation and gene regulation during Drosophila dorsoventral patterning

Multiplex-GAM: genome-wide identification of chromatin contacts yields insights not captured by Hi-C

CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression

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