HiCArch: A Deep Learning-based Hi-C Data Predictor

Hi-C sequencing analysis is one of the most popular methods to study three-dimensional (3D) genome structures, which affect the gene expression and other cellular activities by allowing distal regulations in spatial proximity. Hi-C sequencing analysis enhances understanding of chromatin functionality. However, due to the high cost of Hi-C sequencing, the publicly available Hi-C data of high resolutions (such as 10kb) are limited in only a few cell types. In this paper we present HiCArch, a light-weight deep neural network that predicts Hi-C contact matrices from 11 common 1D epigenomic features. HiCArch identifies topological associated domains (TADs) of 10kb resolution within the distance of 10Mb. HiCArch obtains train Pearson correlation score at 0.9123 and test Pearson correlation score at 0.9195 when trained on K562 cell line. which are significantly higher than previous approaches, such as HiC-Reg, Akita, DeepC, and Epiphany.

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Adenine DNA methylation, 3D genome organization, and gene expression in the parasiteTrichomonas vaginalis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1917286117 ◽

2020 ◽

Vol 117 (23) ◽

pp. 13033-13043

Author(s):

Ayelen Lizarraga ◽

Zach Klapholz O’Brown ◽

Konstantinos Boulias ◽

Lara Roach ◽

Eric Lieberman Greer ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Trichomonas Vaginalis ◽

Three Dimensional ◽

Wide Distribution ◽

Spatial Proximity ◽

Regulation Of Transcription ◽

3D Genome ◽

Intergenic Regions ◽

Close Spatial Proximity

Trichomonas vaginalisis a common sexually transmitted parasite that colonizes the human urogenital tract causing infections that range from asymptomatic to highly inflammatory. Recent works have highlighted the importance of histone modifications in the regulation of transcription and parasite pathogenesis. However, the nature of DNA methylation in the parasite remains unexplored. Using a combination of immunological techniques and ultrahigh-performance liquid chromatography (UHPLC), we analyzed the abundance of DNA methylation in strains with differential pathogenicity demonstrating that N6-methyladenine (6mA), and not 5‐methylcytosine (5mC), is the main DNA methylation mark inT. vaginalis. Genome-wide distribution of 6mA reveals that this mark is enriched at intergenic regions, with a preference for certain superfamilies of DNA transposable elements. We show that 6mA inT. vaginalisis associated with silencing when present on genes. Interestingly, bioinformatics analysis revealed the presence of transcriptionally active or repressive intervals flanked by 6mA-enriched regions, and results from chromatin conformation capture (3C) experiments suggest these 6mA flanked regions are in close spatial proximity. These associations were disrupted when parasites were treated with the demethylation activator ascorbic acid. This finding revealed a role for 6mA in modulating three-dimensional (3D) chromatin structure and gene expression in this divergent member of the Excavata.

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MyoD is a structure organizer of 3D genome architecture in muscle cells

10.1101/2020.08.29.273375 ◽

2020 ◽

Author(s):

Qian Chen ◽

Fengling Chen ◽

Ruiting Wang ◽

Minglei Shi ◽

Antony K. Chen ◽

...

Keyword(s):

Genome Organization ◽

Three Dimensional ◽

Muscle Cells ◽

Cell Types ◽

Linear Molecule ◽

Basic Question ◽

Genome Architecture ◽

Cell Type ◽

3D Genome ◽

A Genome

AbstractThe genome is not a linear molecule of DNA randomly folded in the nucleus, but exists as an organized, three-dimensional (3D) dynamic architecture. Intriguingly, it is now clear that each cell type has a unique and characteristic 3D genome organization that functions in determining cell identity during development. A currently challenging basic question is how cell-type specific 3D genome structures are established during development. Herein, we analyzed 3D genome structures in primary myoblasts and myocytes from MyoD knockout (MKO) and wild type (WT) mice and discovered that MyoD, a pioneer transcription factor (TF), can function as a “genome organizer” that specifies the proper 3D genome architecture unique to muscle cell development. Importantly, we genetically demonstrate that H3K27ac is insufficient for establishing MyoD-induced chromatin loops in muscle cells. The establishment of MyoD’s “architectural role” should have profound impacts on advancing understanding of other pioneer transcription factors in orchestrating lineage specific 3D genome organization during development in a potentially very large number of cell types in diverse organisms.

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A CRISPR Screen Identifies Myc-associated Zinc Finger Protein (MAZ) as an Insulator Functioning at CTCF boundaries in Hox Clusters

10.1101/2020.08.25.267237 ◽

2020 ◽

Author(s):

Havva Ortabozkoyun-Kara ◽

Pin-Yao Huang ◽

Hyunwoo Cho ◽

Varun Narendra ◽

Gary Leroy ◽

...

Keyword(s):

Zinc Finger ◽

Zinc Finger Protein ◽

Three Dimensional ◽

Embryonic Stem ◽

Cell Types ◽

Ctcf Binding ◽

3D Genome ◽

Finger Protein ◽

A Genome ◽

Architectural Organization

AbstractThe essential CCCTC-binding factor (CTCF) is critical to three-dimensional (3D) genome organization. CTCF binding insulates active and repressed genes within the Hox clusters upon differentiation, but such binding does not participate in boundary formation in all cell types, such as embryonic stem cells. We conducted a genome-wide CRISPR knockout screen to identify genes required for CTCF boundary activity at the HoxA cluster, complemented by novel biochemical approaches. This screen identified Myc-associated zinc finger protein (MAZ) as a CTCF insulator co-factor, among other candidates listed herein. MAZ depletion or specific deletion of MAZ motifs within the Hox clusters led to de-repression of posterior Hox genes immediately after CTCF boundaries upon differentiation, which phenocopied deletion of the proximal CTCF motifs. Similar to CTCF, MAZ interacted with the cohesin subunit, RAD21. Upon loss of MAZ, local contacts within topologically associated domains (TADs) were disrupted, as evidenced by HiC analysis. Thus, MAZ is a novel factor sharing insulation properties with CTCF and contributing to the genomic architectural organization.One Sentence SummaryMAZ is identified as an insulator functioning at CTCF boundaries delimiting active and repressed genes at Hox clusters

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SEM of Hepatocytes and Biliary Passages in Goldfish Liver

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100080213 ◽

1977 ◽

Vol 35 ◽

pp. 556-557

Author(s):

Waykin Nopanitaya ◽

Joe W. Grisham ◽

Johnny L. Carson

Keyword(s):

Carassius Auratus ◽

Cell Layer ◽

Three Dimensional ◽

Cell Types ◽

Biliary System ◽

Fish Food ◽

Commercial Fish ◽

Goldfish Carassius Auratus ◽

Commercial Fish Food

An interesting feature of the goldfish liver is the morphology of the hepatic plate, which is always formed by a two-cell layer of hepatocytes. Hepatic plates of the goldfish liver contain an infrequently seen second type of cell, in the centers of plates between two hepatocytes. A TEH study by Yamamoto (1) demonstrated ultrastructural differences between hepatocytes and centrally located cells in hepatic plates; the latter were classified as ductule cells of the biliary system. None of the previous studies clearly showed a three-dimensional organization of the two cell types described. In the present investigation we utilize SEM to elucidate the arrangement of hepatocytes and bile ductular cells in intralobular plates of goldfish liver.Livers from young goldfish (Carassius auratus), about 6-10 cm, fed commercial fish food were used for this study. Hepatic samples were fixed in 4% buffered paraformaldehyde, cut into pieces, fractured, osmicated, CPD, mounted Au-Pd coated, and viewed by SEM at 17-20 kV. Our observations were confined to the ultrastructure of biliary passages within intralobular plates, ductule cells, and hepatocytes.

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Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180410125850 ◽

2018 ◽

Vol 18 (4) ◽

pp. 246-255 ◽

Cited By ~ 1

Author(s):

Lara Termini ◽

Enrique Boccardo

Keyword(s):

Three Dimensional ◽

Cell Types ◽

Experimental Models ◽

Biological Research ◽

Specific Gene ◽

Specific Cell ◽

Organotypic Cultures ◽

Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

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In situ differentiation of iridophore crystallotypes underlies zebrafish stripe patterning

Nature Communications ◽

10.1038/s41467-020-20088-1 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Dvir Gur ◽

Emily J. Bain ◽

Kory R. Johnson ◽

Andy J. Aman ◽

H. Amalia Pasoili ◽

...

Keyword(s):

Skin Color ◽

Cell Types ◽

Color Pattern ◽

Single Type ◽

Sequencing Analysis ◽

X Ray Diffraction ◽

X Ray ◽

Cryogenic Scanning Electron Microscopy ◽

Different Cell Types

AbstractSkin color patterns are ubiquitous in nature, impact social behavior, predator avoidance, and protection from ultraviolet irradiation. A leading model system for vertebrate skin patterning is the zebrafish; its alternating blue stripes and yellow interstripes depend on light-reflecting cells called iridophores. It was suggested that the zebrafish’s color pattern arises from a single type of iridophore migrating differentially to stripes and interstripes. However, here we find that iridophores do not migrate between stripes and interstripes but instead differentiate and proliferate in-place, based on their micro-environment. RNA-sequencing analysis further reveals that stripe and interstripe iridophores have different transcriptomic states, while cryogenic-scanning-electron-microscopy and micro-X-ray diffraction identify different crystal-arrays architectures, indicating that stripe and interstripe iridophores are different cell types. Based on these results, we present an alternative model of skin patterning in zebrafish in which distinct iridophore crystallotypes containing specialized, physiologically responsive, organelles arise in stripe and interstripe by in-situ differentiation.

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Three-dimensional light-weight piezoresistive sensors based on conductive polyurethane sponges coated with hybrid CNT/CB nanoparticles

Applied Surface Science ◽

10.1016/j.apsusc.2021.149268 ◽

2021 ◽

Vol 548 ◽

pp. 149268

Author(s):

Litao Huang ◽

Jianwen Chen ◽

Youquan Xu ◽

Dengwen Hu ◽

Xihua Cui ◽

...

Keyword(s):

Three Dimensional ◽

Light Weight ◽

Piezoresistive Sensors

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The patellofemoral morphology and the normal predicted value of tibial tuberosity-trochlear groove distance in the Chinese population

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04454-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zhe Li ◽

Guanzhi Liu ◽

Run Tian ◽

Ning Kong ◽

Yue Li ◽

...

Keyword(s):

Individual Differences ◽

Chinese Population ◽

Pearson Correlation ◽

Three Dimensional ◽

Correlation Coefficients ◽

Tibial Tuberosity ◽

Trochlear Groove ◽

Lasso Regression ◽

Cross Sectional ◽

Anterior Posterior

Abstract Background Our objective was to obtain normal patellofemoral measurements to analyse sex and individual differences. In addition, the absolute values and indices of tibial tuberosity-trochlear groove (TT-TG) distances are still controversial in clinical application. A better method to enable precise prediction is still needed. Methods Seventy-eight knees of 78 participants without knee pathologies were included in this cross-sectional study. A CT scan was conducted for all participants and three-dimensional knee models were constructed using Mimics and SolidWorks software. We measured and analysed 19 parameters including the TT-TG distance and dimensions and shapes of the patella, femur, tibia, and trochlea. LASSO regression was used to predict the normal TT-TG distances. Results The dimensional parameters, TT-TG distance, and femoral aspect ratio of the men were significantly larger than those of women (all p values < 0.05). However, after controlling for the bias from age, height, and weight, there were no significant differences in TT-TG distances and anterior-posterior dimensions between the sexes (all p values > 0.05). The Pearson correlation coefficients between the anterior femoral offset and other indexes were consistently below 0.3, indicating no relationship or a weak relationship. Similar results were observed for the sulcus angle and the Wiberg index. Using LASSO regression, we obtained four parameters to predict the TT-TG distance (R2 = 0.5612, p < 0.01) to achieve the optimal accuracy and convenience. Conclusions Normative data of patellofemoral morphology were provided for the Chinese population. The anterior-posterior dimensions of the women were thicker than those of men for the same medial-lateral dimensions. More attention should be paid to not only sex differences but also individual differences, especially the anterior condyle and trochlea. In addition, this study provided a new method to predict TT-TG distances accurately.

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3DIV update for 2021: a comprehensive resource of 3D genome and 3D cancer genome

Nucleic Acids Research ◽

10.1093/nar/gkaa1078 ◽

2020 ◽

Vol 49 (D1) ◽

pp. D38-D46

Author(s):

Kyukwang Kim ◽

Insu Jang ◽

Mooyoung Kim ◽

Jinhyuk Choi ◽

Min-Seo Kim ◽

...

Keyword(s):

Cell Line ◽

Large Scale ◽

Three Dimensional ◽

Cancer Cell Line ◽

Cancer Genome ◽

Structural Variations ◽

3D Genome ◽

Tightly Coupled ◽

Regulatory Effects ◽

The Impact

Abstract Three-dimensional (3D) genome organization is tightly coupled with gene regulation in various biological processes and diseases. In cancer, various types of large-scale genomic rearrangements can disrupt the 3D genome, leading to oncogenic gene expression. However, unraveling the pathogenicity of the 3D cancer genome remains a challenge since closer examinations have been greatly limited due to the lack of appropriate tools specialized for disorganized higher-order chromatin structure. Here, we updated a 3D-genome Interaction Viewer and database named 3DIV by uniformly processing ∼230 billion raw Hi-C reads to expand our contents to the 3D cancer genome. The updates of 3DIV are listed as follows: (i) the collection of 401 samples including 220 cancer cell line/tumor Hi-C data, 153 normal cell line/tissue Hi-C data, and 28 promoter capture Hi-C data, (ii) the live interactive manipulation of the 3D cancer genome to simulate the impact of structural variations and (iii) the reconstruction of Hi-C contact maps by user-defined chromosome order to investigate the 3D genome of the complex genomic rearrangement. In summary, the updated 3DIV will be the most comprehensive resource to explore the gene regulatory effects of both the normal and cancer 3D genome. ‘3DIV’ is freely available at http://3div.kr.

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Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery

International Journal of Molecular Sciences ◽

10.3390/ijms22031203 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1203

Author(s):

Lu Qian ◽

Julia TCW

Keyword(s):

Drug Discovery ◽

Disease Modeling ◽

Three Dimensional ◽

Structural Complexity ◽

Induced Pluripotent Stem Cell ◽

Cell Types ◽

Central Nerve System ◽

Human Ipscs ◽

Nerve System

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients’ CNS and serve as a platform for therapeutic development and personalized precision medicine.

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