Integrating Hi-C and FISH data for modeling of the 3D organization of chromosomes

Abbas, Ahmed; He, Xuan; Niu, Jing; Zhou, Bin; Zhu, Guangxiang; Ma, Tszshan; Song, Jiangpeikun; Gao, Juntao; Zhang, Michael Q.; Zeng, Jianyang

doi:10.1038/s41467-019-10005-6

Cited by 54 publications

(39 citation statements)

References 60 publications

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“…The approach does not rely on the multidimensional scaling approximation (MDS), which infers 3D distances based on measured contact frequency. 47 We adapted the polymer bead-spring model from Kremer and Grest – a widely used polymer physics model that describes a polymer as beads connected by springs 48,49 . Our Hi-C datasets for X inactivation have a resolution of 200 kb.…”

Section: Resultsmentioning

confidence: 99%

4D chromosome reconstruction elucidates the spatial reorganization of the mammalian X-chromosome

Lappala

Wang

Kriz

et al. 2021

Preprint

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Chromosomes are segmented into domains and compartments; yet, how these structures are spatially related in 3D is unclear. Here, by directly integrating Hi-C capture experiments and 3D modeling, we use X-inactivation as a model to examine the time evolution of 3D chromosome architecture during substantial changes in gene expression. First, we show that gene expression A/B compartments are consistent with phase separation in 3D space. Second, we show that residuals of smaller scale structures persist through transitions, despite further large-scale reorganization into the final inactive configuration, comprising two “megadomains”. Interestingly, these previously hidden residual structures were not detectable in 2D Hi-C maps or principal component analyses. Third, time-dependent reaction-diffusion simulations reveal how Xist RNA particles diffuse across the 3D X-superstructure as it reorganizes. Our 4DHiC pipeline helps satisfy the growing demand for methodologies that produce 3D chromosome reconstructions directly from 2D datasets, which are consistent with the empirical data.

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Section: Resultsmentioning

confidence: 99%

4D chromosome reconstruction elucidates the spatial reorganization of the mammalian X-chromosome

Lappala

Wang

Kriz

et al. 2021

Preprint

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“… 42 Integration of Hi-C data with conventional microscopy led to more accurate prediction of genome organization. 50 More recently, Hi-C data and super-resolution imaging were brought together through integrative modeling of genomic regions (IMGR), thus achieving high spatial and genomic resolution, while maintaining the single-cell identity. 51 – 53 IMGR can be broadly divided into three steps.…”

Section: Genes Of Targeted Pathways Should Be Accessiblementioning

confidence: 99%

A new precision medicine initiative at the dawn of exascale computing

Nussinov

Jang

Nir

et al. 2021

Sig Transduct Target Ther

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Which signaling pathway and protein to select to mitigate the patient’s expected drug resistance? The number of possibilities facing the physician is massive, and the drug combination should fit the patient status. Here, we briefly review current approaches and data and map an innovative patient-specific strategy to forecast drug resistance targets that centers on parallel (or redundant) proliferation pathways in specialized cells. It considers the availability of each protein in each pathway in the specific cell, its activating mutations, and the chromatin accessibility of its encoding gene. The construction of the resulting Proliferation Pathway Network Atlas will harness the emerging exascale computing and advanced artificial intelligence (AI) methods for therapeutic development. Merging the resulting set of targets, pathways, and proteins, with current strategies will augment the choice for the attending physicians to thwart resistance.

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“…Purported to be robust against noise [8], it should be noted that noise and experimentally induced biases are highly nontrivial to handle. To mitigate this, contact based approaches have incorporated other sources of data such as fluorescence in situ hybridization (FISH) [22] as well as Lamina-associated Domains (LADs) [23].…”

Section: The Genome Reconstruction Problemmentioning

confidence: 99%

ChromeBat: A Bio-Inspired Approach to 3D Genome Reconstruction

Collins

Brown

Oluwadare

2021

Preprint

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Background: With the advent of Next Generation Sequencing and the Hi-C experiment, high quality genome-wide contact data is becoming increasingly available. This data represents an empirical measure of how a genome interacts inside the nucleus. Genome conformation is of particular interest as it has been experimentally shown to be a driving force for many genomic functions from regulation to transcription. Thus, the Three-Dimensional Genome Reconstruction Problem seeks to take Hi-C data and produce the complete physical genome structure as it appears in the nucleus for genomic analysis. Results: We propose and develop a novel method to solve the Chromosome and Genome Reconstruction problem based on the Bat Algorithm which we called ChromeBat.We demonstrate on real Hi-C data that ChromeBat is capable of state of the art performance. Additionally, the domain of Genome Reconstruction has been criticized for lacking algorithmic diversity, and the bio-inspired nature of ChromeBat contributes algorithmic diversity to the problem domain. Conclusions: ChromeBat is an effective approach at solving the Genome Reconstruction Problem. The source code and usage guide can be found here: https://github.com/OluwadareLab/ChromeBat.

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Integrating Hi-C and FISH data for modeling of the 3D organization of chromosomes

Cited by 54 publications

References 60 publications

4D chromosome reconstruction elucidates the spatial reorganization of the mammalian X-chromosome

4D chromosome reconstruction elucidates the spatial reorganization of the mammalian X-chromosome

A new precision medicine initiative at the dawn of exascale computing

ChromeBat: A Bio-Inspired Approach to 3D Genome Reconstruction

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