HiGlass: Web-based Visual Exploration and Analysis of Genome Interaction Maps

Kerpedjiev, Peter; Abdennur, Nezar; Lekschas, Fritz; McCallum, Chuck; Dinkla, Kasper; Strobelt, Hendrik; Luber, Jacob M.; Ouellette, Scott; Azhir, Alaleh; Kumar, Nikhil; Hwang, Jeewon; Lee, Mi Kyung; Alver, B.; Pfister, Hanspeter; Mirny, Leonid A.; Park, Peter J.; Gehlenborg, Nils

doi:10.1101/121889

Cited by 159 publications

(199 citation statements)

References 55 publications

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“…Rao et al also identified intriguing emergent “loop” cliques enriched in super-enhancers upon cohesin depletion 37 . We also observed such features in our primary hepatocytes using a new Hi-C browser 38 , though we note that in both cases these patterns do not resemble the sharp cis -only focal patterns of CTCF-associated Hi-C peaks commonly referred to as loops 12 . Rather, these larger patches appear to be enhanced compartmental interactions between very active regions that line up well with actively transcribed genes 38 .…”

Section: Cohesin Is Central To Chromosome Foldingmentioning

confidence: 72%

Two independent modes of chromatin organization revealed by cohesin removal

Schwarzer

Abdennur

Goloborodko

et al. 2017

Nature

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1,052

114

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Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-large active and inactive compartments, and partitioning into sub-megabase domains (TADs). Yet, it remains unclear how these layers of organization form, interact with one another and impact genome functions. Here, we show that deletion of the cohesin-loading factor Nipbl, in mouse liver, leads to a dramatic reorganization of chromosomal folding. TADs and associated peaks vanish globally, even in the absence of transcriptional changes. In contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the 3D organization of the genome results from the interplay of two independent mechanisms: 1) cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; 2) cohesin-dependent formation of TADs, possibly by loop extrusion, which contributes to guide distant enhancers to their target genes.

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Section: Cohesin Is Central To Chromosome Foldingmentioning

confidence: 72%

Two independent modes of chromatin organization revealed by cohesin removal

Schwarzer

Abdennur

Goloborodko

et al. 2017

Nature

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1,052

114

1,115

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“…We compared Tiled-C data in mouse ES cells to the deepest currently available Hi-C data in mouse ES cells 5 . We explored the data using HiGlass 44 and downloaded and re-analyzed the Hi-C data using the HiC-Pro pipeline 41 with default options and ICE normalization 42 .…”

Section: Hi-cmentioning

confidence: 99%

Dynamics of the 4D genome during lineage specification, differentiation and maturation in vivo

Oudelaar

Beagrie

Gosden

et al. 2019

Preprint

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Mammalian gene expression patterns are controlled by regulatory elements, which interact within Topologically Associating Domains (TADs). The relationship between activation of regulatory elements, formation of structural chromatin interactions and gene expression during development is unclear. We developed Tiled-C, a low-input Chromosome Conformation Capture (3C) approach, to study chromatin architecture at high spatial and temporal resolution through in vivo mouse erythroid differentiation. Integrated analysis of matched chromatin accessibility and single-cell expression data shows that regulatory elements gradually become accessible within pre-existing TADs during early differentiation. This is followed by structural re-organization within the TAD and formation of specific contacts between enhancers and promoters. In contrast to previous reports, our high-resolution data show that these enhancer-promoter interactions are not established prior to gene expression, but formed gradually during differentiation, concomitant with progressive upregulation of gene activity. Together, these results provide new insight into the close, interdependent relationship between chromatin architecture and gene regulation during development.

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“…Most applications work offline and integrate 1D tracks, which show various genomic measures in the forms of line graphs or bar charts. HiGlass [26] is a web-based interaction matrix and 1D track viewer that additionally provides seamless view manipulation and view sharing. We integrated HiGlass into HiPiler to provide an overview of the snippet locations, to display 1D tracks, and to select and highlight snippets from the interaction matrix.…”

Section: Related Workmentioning

confidence: 99%

“…It is possible to fade out snippets that are not visible in the viewport of the detail matrix to provide more focus. Also, HiGlass [26] supports 1D genomic tracks, which enables experts to correlate patterns to many other genomic measures (T5). Finally, the matrix view can host more than one matrix to support comparison across datasets (T6).…”

Section: Design Of Hipilermentioning

confidence: 99%

“…Interactive visualization tools have been developed [45] but are focused on supporting visualization of a single or a small number of views of the matrix and navigation through pan and zoom [14, 26]. However, detailed exploration and comparison of thousands of small ROIs is unsupported by current tools yet needed, due to the size and multi-scale nature of the folded genome.…”

Section: Introductionmentioning

confidence: 99%

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HiPiler: Visual Exploration of Large Genome Interaction Matrices with Interactive Small Multiples

Lekschas

Bach

Kerpedjiev

et al. 2018

IEEE Trans. Visual. Comput. Graphics

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This paper presents an interactive visualization interface—HiPiler—for the exploration and visualization of regions-of-interest in large genome interaction matrices. Genome interaction matrices approximate the physical distance of pairs of regions on the genome to each other and can contain up to 3 million rows and columns with many sparse regions. Regions of interest (ROIs) can be defined, e.g., by sets of adjacent rows and columns, or by specific visual patterns in the matrix. However, traditional matrix aggregation or pan-and-zoom interfaces fail in supporting search, inspection, and comparison of ROIs in such large matrices. In HiPiler, ROIs are first-class objects, represented as thumbnail-like “snippets”. Snippets can be interactively explored and grouped or laid out automatically in scatterplots, or through dimension reduction methods. Snippets are linked to the entire navigable genome interaction matrix through brushing and linking. The design of HiPiler is based on a series of semi-structured interviews with 10 domain experts involved in the analysis and interpretation of genome interaction matrices. We describe six exploration tasks that are crucial for analysis of interaction matrices and demonstrate how HiPiler supports these tasks. We report on a user study with a series of data exploration sessions with domain experts to assess the usability of HiPiler as well as to demonstrate respective findings in the data.

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HiGlass: Web-based Visual Exploration and Analysis of Genome Interaction Maps

Cited by 159 publications

References 55 publications

Two independent modes of chromatin organization revealed by cohesin removal

Two independent modes of chromatin organization revealed by cohesin removal

Dynamics of the 4D genome during lineage specification, differentiation and maturation in vivo

HiPiler: Visual Exploration of Large Genome Interaction Matrices with Interactive Small Multiples

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