The 4D Nucleome Data Portal: a resource for searching and visualizing curated nucleomics data

Reiff, Sarah B.; Schroeder, Andrew J.; Kırlı, Koray; Cosolo, Andrea; Bakker, Clara; Mercado, Luisa; Lee, Soohyun; Veit, Alexander D.; Balashov, Alexander; Vitzthum, Carl; Ronchetti, William; Pitman, Kent M.; Johnson, Jeremy; Ehmsen, Shannon; Kerpedjiev, Peter; Abdennur, Nezar; Imakaev, Maxim; Öztürk, Serkan Utku; Çamoğlu, Uğur; Mirny, Leonid A.; Gehlenborg, Nils; Alver, B.; Park, Peter J.

doi:10.1101/2021.10.14.464435

Cited by 19 publications

(28 citation statements)

References 60 publications

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“…The first step in the optimization procedure is running Stripenn v1.1.65.5 [60] on the H1-hESC Micro-C (4DNFI9GMP2J8 [62], [63]) dataset to identify architectural stripes, which resulted in the identification of 4930 stripes. A small subset of these stripes were visually validated by comparing the annotated stripes with stripes that are visible from Micro-C data.…”

Section: Methodsmentioning

confidence: 99%

“…H1-hESC Micro-C data in multi-resolution cooler format (4DNFI9GMP2J8 [62]) were downloaded from the 4DNucleome Data Portal [63].…”

Section: Availability Of Data and Materialsmentioning

confidence: 99%

“…The genome-wide optimization of parameters affecting extrusion barrier occupancies was carried out using the optimize_MoDLE_sim_params Nextflow workflow available on GitHub and archived on Zenodo [45,46]. The first step in the optimization procedure is running Stripenn v1.1.65.5 [60] on the H1-hESC Micro-C (4DNFI9GMP2J8 [62], [63]) dataset to identify architectural stripes, which resulted in the identification of 4930 stripes. A small subset of these stripes were visually validated by comparing the annotated stripes with stripes that are visible from Micro-C data.…”

Section: Genome-wide Extrusion Barrier Parameter Optimizationmentioning

confidence: 99%

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MoDLE: High-performance stochastic modeling of DNA loop extrusion interactions

Rossini

Kumar

Mathelier

et al. 2022

Preprint

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DNA loop extrusion emerges as a key process establishing genome structure and function. We introduce MoDLE, a computational tool for fast, stochastic modeling of molecular contacts from DNA loop extrusion capable of simulating realistic contact patterns genome wide in a few minutes. MoDLE accurately simulates contact maps in concordance with existing molecular dynamics approaches and with Micro-C data, and does so orders of magnitude faster than existing approaches. MoDLE runs efficiently on machines ranging from laptops to high performance computing clusters, and opens up for exploratory and predictive modeling of 3D genome structure in a wide range of settings.

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Section: Methodsmentioning

confidence: 99%

“…H1-hESC Micro-C data in multi-resolution cooler format (4DNFI9GMP2J8 [62]) were downloaded from the 4DNucleome Data Portal [63].…”

Section: Availability Of Data and Materialsmentioning

confidence: 99%

Section: Genome-wide Extrusion Barrier Parameter Optimizationmentioning

confidence: 99%

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MoDLE: High-performance stochastic modeling of DNA loop extrusion interactions

Rossini

Kumar

Mathelier

et al. 2022

Preprint

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“…(i) Visualizing imaging data from 4DN. We developed a special web component to display imaging data hosted on the 4DN data portal (https://data.4dnucleome.org) [23]. We first compiled meta-information associated with imaging data on the 4DN data portal, extracted imaging datasets containing genomic coordinates information, and saved meta-information into a local database using the binning index algorithm for fast query of images for queries.…”

Section: Visualizing Imaging Data In Nucleome Browsermentioning

confidence: 99%

Nucleome Browser: An integrative and multimodal data navigation platform for 4D Nucleome

Zhu

Zhang

Wang

et al. 2022

Preprint

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We introduce Nucleome Browser (http://www.nucleome.org), an interactive, multimodal data visualization and exploration platform for 4D Nucleome research. Our tool effectively integrates heterogeneous datasets (e.g., genomics, imaging, 3D genome structure models, and single-cell data) and external data portals by a new adaptive communication mechanism. Nucleome Browser provides a scalable solution for integrating massive amounts of 4D Nucleome data to navigate multiscale nuclear structure and function in a wide range of biological contexts, enabling hypothesis generation and data sharing with the broad community.

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“…To do this, we wrote two python codes, one for generating the coordinates according to the "same subcompartment ChIP-Seq peaks' crossings" in the trans region and the other for doing the pileup, including calculating the averaged trans-pileup-matrix (hereafter referred to as trans-pileup-matrix). With these two python codes we pulled the available ChIP-Seq data of the GM12878 cells from the Encode data portal (49,50) and in-situ Hi-C (MboI) for GM12878 (Lieberman Aiden Lab) mcool file from 4DN data portal (51,52) to do the pileup. From the all the plotted pileup matrices (Supplementary Figure 9d, Supplementary Material), we did not see the classical loop pattern seen in the diagonal of the Hi-C matrix, which were known to be mediated by CTCF and cohesin (6,(53)(54)(55)(56) and the fine loop pattern seen in ultra-resolution micro-C matrix, which was prove to be mediated by transcriptional activity (7).…”

Section: Relationship Between Nucleoprotein Binding Sites and Trans C...mentioning

confidence: 99%

Cryomilling Tethered Chromatin Conformation Capture reveal new insights into inter-chromosomal interactions

Kumar

Nan

et al. 2022

Preprint

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Traditional methods used to map the three-dimensional organization of chromatin in-situ generally involve chromatin conformation capture by formaldehyde crosslinking, followed by detergent solubilization and enzymatic digestion of DNA. Ligation of proximal DNA fragments followed by next generation sequencing (NGS) generates contact information that enables a global view of the chromatin conformation. Here, we explore the use of cryomilling to physically fragmentize the cells under cryogenic conditions to probe chromatin interactions in the cryomilled cell fragments by the tethered chromatin conformation capture (TCC). Our results show that cryomilling TCC (CTCC) can generate a global contact map similar to that obtained with in-situ Hi-C. This result suggests that summation of chromatin interactions mapped in individual subcellular fragments can reconstitute the global contact map of intact cells in an ensemble manner, paving the way for chromatin conformation analyses of solid tissue by CTCC. Compared with the conventional in-situ methods such as Hi-C, CTCC shows more uniform access to different subcompartments of the folded genome. On the other hand, most inter-chromosomal (trans) contacts are diminished or lost in CTCC except for a group of unique trans contacts that remain intact throughout the cryomilling and in-vitro crosslinking steps. These apparently ultra-stable trans interactions have much enhanced signal in CTCC due to the elimination of signals of most, presumably weak and transient trans interactions. Systematic and comparative analyses between CTCC and in-situ Hi-C provide further insights into the chromatin structure organization and reveal a generally unentangled chromosome interface and the existence of stable inter-chromosomal contacts that may represent intermingled inter-chromosomal interfaces.

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The 4D Nucleome Data Portal: a resource for searching and visualizing curated nucleomics data

Cited by 19 publications

References 60 publications

MoDLE: High-performance stochastic modeling of DNA loop extrusion interactions

MoDLE: High-performance stochastic modeling of DNA loop extrusion interactions

Nucleome Browser: An integrative and multimodal data navigation platform for 4D Nucleome

Cryomilling Tethered Chromatin Conformation Capture reveal new insights into inter-chromosomal interactions

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