Artículos de revistas: "3D genome structure"

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Zhou, Tianming, Ruochi Zhang y Jian Ma. "The 3D Genome Structure of Single Cells". Annual Review of Biomedical Data Science 4, n.º 1 (20 de julio de 2021): 21–41. http://dx.doi.org/10.1146/annurev-biodatasci-020121-084709.

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The spatial organization of the genome in the cell nucleus is pivotal to cell function. However, how the 3D genome organization and its dynamics influence cellular phenotypes remains poorly understood. The very recent development of single-cell technologies for probing the 3D genome, especially single-cell Hi-C (scHi-C), has ushered in a new era of unveiling cell-to-cell variability of 3D genome features at an unprecedented resolution. Here, we review recent developments in computational approaches to the analysis of scHi-C, including data processing, dimensionality reduction, imputation for enhancing data quality, and the revealing of 3D genome features at single-cell resolution. While much progress has been made in computational method development to analyze single-cell 3D genomes, substantial future work is needed to improve data interpretation and multimodal data integration, which are critical to reveal fundamental connections between genome structure and function among heterogeneous cell populations in various biological contexts.

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Mohanta, Tapan Kumar, Awdhesh Kumar Mishra y Ahmed Al-Harrasi. "The 3D Genome: From Structure to Function". International Journal of Molecular Sciences 22, n.º 21 (27 de octubre de 2021): 11585. http://dx.doi.org/10.3390/ijms222111585.

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The genome is the most functional part of a cell, and genomic contents are organized in a compact three-dimensional (3D) structure. The genome contains millions of nucleotide bases organized in its proper frame. Rapid development in genome sequencing and advanced microscopy techniques have enabled us to understand the 3D spatial organization of the genome. Chromosome capture methods using a ligation approach and the visualization tool of a 3D genome browser have facilitated detailed exploration of the genome. Topologically associated domains (TADs), lamin-associated domains, CCCTC-binding factor domains, cohesin, and chromatin structures are the prominent identified components that encode the 3D structure of the genome. Although TADs are the major contributors to 3D genome organization, they are absent in Arabidopsis. However, a few research groups have reported the presence of TAD-like structures in the plant kingdom.

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Huang, Kai, Yue Li, Anne R. Shim, Ranya K. A. Virk, Vasundhara Agrawal, Adam Eshein, Rikkert J. Nap, Luay M. Almassalha, Vadim Backman y Igal Szleifer. "Physical and data structure of 3D genome". Science Advances 6, n.º 2 (enero de 2020): eaay4055. http://dx.doi.org/10.1126/sciadv.aay4055.

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With the textbook view of chromatin folding based on the 30-nm fiber being challenged, it has been proposed that interphase DNA has an irregular 10-nm nucleosome polymer structure whose folding philosophy is unknown. Nevertheless, experimental advances suggest that this irregular packing is associated with many nontrivial physical properties that are puzzling from a polymer physics point of view. Here, we show that the reconciliation of these exotic properties necessitates modularizing three-dimensional genome into tree data structures on top of, and in striking contrast to, the linear topology of DNA double helix. These functional modules need to be connected and isolated by an open backbone that results in porous and heterogeneous packing in a quasi–self-similar manner, as revealed by our electron and optical imaging. Our multiscale theoretical and experimental results suggest the existence of higher-order universal folding principles for a disordered chromatin fiber to avoid entanglement and fulfill its biological functions.

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4

Heinz, Sven, Lorane Texari, Michael G. B. Hayes, Matthew Urbanowski, Max W. Chang, Ninvita Givarkes, Alexander Rialdi et al. "Transcription Elongation Can Affect Genome 3D Structure". Cell 174, n.º 6 (septiembre de 2018): 1522–36. http://dx.doi.org/10.1016/j.cell.2018.07.047.

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Wlasnowolski, Michal, Michal Sadowski, Tymon Czarnota, Karolina Jodkowska, Przemyslaw Szalaj, Zhonghui Tang, Yijun Ruan y Dariusz Plewczynski. "3D-GNOME 2.0: a three-dimensional genome modeling engine for predicting structural variation-driven alterations of chromatin spatial structure in the human genome". Nucleic Acids Research 48, W1 (22 de mayo de 2020): W170—W176. http://dx.doi.org/10.1093/nar/gkaa388.

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Abstract Structural variants (SVs) that alter DNA sequence emerge as a driving force involved in the reorganisation of DNA spatial folding, thus affecting gene transcription. In this work, we describe an improved version of our integrated web service for structural modeling of three-dimensional genome (3D-GNOME), which now incorporates all types of SVs to model changes to the reference 3D conformation of chromatin. In 3D-GNOME 2.0, the default reference 3D genome structure is generated using ChIA-PET data from the GM12878 cell line and SVs data are sourced from the population-scale catalogue of SVs identified by the 1000 Genomes Consortium. However, users may also submit their own structural data to set a customized reference genome structure, and/or a custom input list of SVs. 3D-GNOME 2.0 provides novel tools to inspect, visualize and compare 3D models for regions that differ in terms of their linear genomic sequence. Contact diagrams are displayed to compare the reference 3D structure with the one altered by SVs. In our opinion, 3D-GNOME 2.0 is a unique online tool for modeling and analyzing conformational changes to the human genome induced by SVs across populations. It can be freely accessed at https://3dgnome.cent.uw.edu.pl/.

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6

Shepherd, Jeremiah J., Lingxi Zhou, William Arndt, Yan Zhang, W. Jim Zheng y Jijun Tang. "Exploring genomes with a game engine". Faraday Discuss. 169 (2014): 443–53. http://dx.doi.org/10.1039/c3fd00152k.

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More and more evidence indicates that the 3D conformation of eukaryotic genomes is a critical part of genome function. However, due to the lack of accurate and reliable 3D genome structural data, this information is largely ignored and most of these studies have to use information systems that view the DNA in a linear structure. Visualizing genomes in real time 3D can give researchers more insight, but this is fraught with hardware limitations since each element contains vast amounts of information that cannot be processed on the fly. Using a game engine and sophisticated video game visualization techniques enables us to construct a multi-platform real-time 3D genome viewer. The game engine-based viewer achieves much better rendering speed and can handle much larger amounts of data compared to our previous implementation using OpenGL. Combining this viewer with 3D genome models from experimental data could provide unprecedented opportunities to gain insight into the conformation–function relationships of a genome.

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Poblete, Simón y Horacio V. Guzman. "Structural 3D Domain Reconstruction of the RNA Genome from Viruses with Secondary Structure Models". Viruses 13, n.º 8 (6 de agosto de 2021): 1555. http://dx.doi.org/10.3390/v13081555.

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Three-dimensional RNA domain reconstruction is important for the assembly, disassembly and delivery functionalities of a packed proteinaceus capsid. However, to date, the self-association of RNA molecules is still an open problem. Recent chemical probing reports provide, with high reliability, the secondary structure of diverse RNA ensembles, such as those of viral genomes. Here, we present a method for reconstructing the complete 3D structure of RNA genomes, which combines a coarse-grained model with a subdomain composition scheme to obtain the entire genome inside proteinaceus capsids based on secondary structures from experimental techniques. Despite the amount of sampling involved in the folded and also unfolded RNA molecules, advanced microscope techniques can provide points of anchoring, which enhance our model to include interactions between capsid pentamers and RNA subdomains. To test our method, we tackle the satellite tobacco mosaic virus (STMV) genome, which has been widely studied by both experimental and computational communities. We provide not only a methodology to structurally analyze the tertiary conformations of the RNA genome inside capsids, but a flexible platform that allows the easy implementation of features/descriptors coming from both theoretical and experimental approaches.

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8

Trieu, Tuan y Jianlin Cheng. "3D genome structure modeling by Lorentzian objective function". Nucleic Acids Research 45, n.º 3 (28 de noviembre de 2016): 1049–58. http://dx.doi.org/10.1093/nar/gkw1155.

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Li, Chao, Xiao Dong, Haiwei Fan, Chuan Wang, Guohui Ding y Yixue Li. "The 3DGD: a database of genome 3D structure". Bioinformatics 30, n.º 11 (12 de febrero de 2014): 1640–42. http://dx.doi.org/10.1093/bioinformatics/btu081.

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10

Tjong, Harianto, Wenyuan Li, Reza Kalhor, Chao Dai, Shengli Hao, Ke Gong, Yonggang Zhou et al. "Population-based 3D genome structure analysis reveals driving forces in spatial genome organization". Proceedings of the National Academy of Sciences 113, n.º 12 (7 de marzo de 2016): E1663—E1672. http://dx.doi.org/10.1073/pnas.1512577113.

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Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm the presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization.

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11

Kim, Kyukwang, Insu Jang, Mooyoung Kim, Jinhyuk Choi, Min-Seo Kim, Byungwook Lee y Inkyung Jung. "3DIV update for 2021: a comprehensive resource of 3D genome and 3D cancer genome". Nucleic Acids Research 49, n.º D1 (27 de noviembre de 2020): D38—D46. http://dx.doi.org/10.1093/nar/gkaa1078.

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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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12

Ohno, Masae, Tadashi Ando, David G. Priest y Yuichi Taniguchi. "Hi-CO: 3D genome structure analysis with nucleosome resolution". Nature Protocols 16, n.º 7 (28 de mayo de 2021): 3439–69. http://dx.doi.org/10.1038/s41596-021-00543-z.

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13

TANIGUCHI, Yuichi y Masae OHNO. "Resolving 3D Higher-order Molecular Structure of the Genome". Seibutsu Butsuri 59, n.º 6 (2019): 305–9. http://dx.doi.org/10.2142/biophys.59.305.

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14

Di Stefano, Marco y Giacomo Cavalli. "Integrative studies of 3D genome organization and chromatin structure". Current Opinion in Structural Biology 77 (diciembre de 2022): 102493. http://dx.doi.org/10.1016/j.sbi.2022.102493.

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15

Kozubek, Stanislav, Emilie Lukásová, Pavla Jirsová, Irena Koutná, Michal Kozubek, Alena Ganová, Eva Bártová, Martin Falk y Renata Paseková. "3D Structure of the human genome: order in randomness". Chromosoma 111, n.º 5 (diciembre de 2002): 321–31. http://dx.doi.org/10.1007/s00412-002-0210-8.

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16

Zhegalova, Irina V., Petr A. Vasiluev, Ilya M. Flyamer, Anastasia S. Shtompel, Eugene Glazyrina, Nadezda Shilova, Marina Minzhenkova et al. "Trisomies Reorganize Human 3D Genome". International Journal of Molecular Sciences 24, n.º 22 (7 de noviembre de 2023): 16044. http://dx.doi.org/10.3390/ijms242216044.

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Trisomy is the presence of one extra copy of an entire chromosome or its part in a cell nucleus. In humans, autosomal trisomies are associated with severe developmental abnormalities leading to embryonic lethality, miscarriage or pronounced deviations of various organs and systems at birth. Trisomies are characterized by alterations in gene expression level, not exclusively on the trisomic chromosome, but throughout the genome. Here, we applied the high-throughput chromosome conformation capture technique (Hi-C) to study chromatin 3D structure in human chorion cells carrying either additional chromosome 13 (Patau syndrome) or chromosome 16 and in cultured fibroblasts with extra chromosome 18 (Edwards syndrome). The presence of extra chromosomes results in systematic changes of contact frequencies between small and large chromosomes. Analyzing the behavior of individual chromosomes, we found that a limited number of chromosomes change their contact patterns stochastically in trisomic cells and that it could be associated with lamina-associated domains (LAD) and gene content. For trisomy 13 and 18, but not for trisomy 16, the proportion of compacted loci on a chromosome is correlated with LAD content. We also found that regions of the genome that become more compact in trisomic cells are enriched in housekeeping genes, indicating a possible decrease in chromatin accessibility and transcription level of these genes. These results provide a framework for understanding the mechanisms of pan-genome transcription dysregulation in trisomies in the context of chromatin spatial organization.

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17

Dias, João Diogo, Nazim Sarica, Axel Cournac, Romain Koszul y Christine Neuveut. "Crosstalk between Hepatitis B Virus and the 3D Genome Structure". Viruses 14, n.º 2 (21 de febrero de 2022): 445. http://dx.doi.org/10.3390/v14020445.

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Viruses that transcribe their DNA within the nucleus have to adapt to the existing cellular mechanisms that govern transcriptional regulation. Recent technological breakthroughs have highlighted the highly hierarchical organization of the cellular genome and its role in the regulation of gene expression. This review provides an updated overview on the current knowledge on how the hepatitis B virus interacts with the cellular 3D genome and its consequences on viral and cellular gene expression. We also briefly discuss the strategies developed by other DNA viruses to co-opt and sometimes subvert cellular genome spatial organization.

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18

Shao, Dan, Yu Yang, Shourong Shi y Haibing Tong. "Three-Dimensional Organization of Chicken Genome Provides Insights into Genetic Adaptation to Extreme Environments". Genes 13, n.º 12 (9 de diciembre de 2022): 2317. http://dx.doi.org/10.3390/genes13122317.

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The high-throughput chromosome conformation capture (Hi-C) technique is widely used to study the functional roles of the three-dimensional (3D) architecture of genomes. However, the knowledge of the 3D genome structure and its dynamics during extreme environmental adaptations remains poor. Here, we characterized 3D genome architectures using the Hi-C technique for chicken liver cells. Upon comparing Lindian chicken (LDC) liver cells with Wenchang chicken (WCC) liver cells, we discovered that environmental adaptation contributed to the switching of A/B compartments, the reorganization of topologically associated domains (TADs), and TAD boundaries in both liver cells. In addition, the analysis of the switching of A/B compartments revealed that the switched compartmental genes (SCGs) were strongly associated with extreme environment adaption-related pathways, including tight junction, notch signaling pathway, vascular smooth muscle contraction, and the RIG-I-like receptor signaling pathway. The findings of this study advanced our understanding of the evolutionary role of chicken 3D genome architecture and its significance in genome activity and transcriptional regulation.

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19

Li, An y Zhang. "The Dynamic 3D Genome in Gametogenesis and Early Embryonic Development". Cells 8, n.º 8 (29 de julio de 2019): 788. http://dx.doi.org/10.3390/cells8080788.

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During gametogenesis and early embryonic development, the chromatin architecture changes dramatically, and both the transcriptomic and epigenomic landscape are comprehensively reprogrammed. Understanding these processes is the holy grail in developmental biology and a key step towards evolution. The 3D conformation of chromatin plays a central role in the organization and function of nuclei. Recently, the dynamics of chromatin structures have been profiled in many model and non-model systems, from insects to mammals, resulting in an interesting comparison. In this review, we first introduce the research methods of 3D chromatin structure with low-input material suitable for embryonic study. Then, the dynamics of 3D chromatin architectures during gametogenesis and early embryonic development is summarized and compared between species. Finally, we discuss the possible mechanisms for triggering the formation of genome 3D conformation in early development.

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20

Dethoff, Elizabeth A., Mark A. Boerneke, Nandan S. Gokhale, Brejnev M. Muhire, Darren P. Martin, Matthew T. Sacco, Michael J. McFadden et al. "Pervasive tertiary structure in the dengue virus RNA genome". Proceedings of the National Academy of Sciences 115, n.º 45 (19 de octubre de 2018): 11513–18. http://dx.doi.org/10.1073/pnas.1716689115.

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RNA virus genomes are efficient and compact carriers of biological information, encoding information required for replication both in their primary sequences and in higher-order RNA structures. However, the ubiquity of RNA elements with higher-order folds—in which helices pack together to form complex 3D structures—and the extent to which these elements affect viral fitness are largely unknown. Here we used single-molecule correlated chemical probing to define secondary and tertiary structures across the RNA genome of dengue virus serotype 2 (DENV2). Higher-order RNA structures are pervasive and involve more than one-third of nucleotides in the DENV2 genomic RNA. These 3D structures promote a compact overall architecture and contribute to viral fitness. Disrupting RNA regions with higher-order structures leads to stable, nonreverting mutants and could guide the development of vaccines based on attenuated RNA viruses. The existence of extensive regions of functional RNA elements with tertiary folds in viral RNAs, and likely many other messenger and noncoding RNAs, means that there are significant regions with pocket-containing surfaces that may serve as novel RNA-directed drug targets.

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21

Zhang, Yan, Yijun Ruan y Guoliang Li. "The 5th International 3D Genomics Workshop 2018: conference report". Epigenomics 11, n.º 12 (septiembre de 2019): 1353–57. http://dx.doi.org/10.2217/epi-2019-0185.

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The International 3D Genomics Workshop is an annual international scientific conference focused on the research of the 3D structure of the genome in the nucleus. The 5th International 3D Genomics Workshop 2018 was held at the International Academic Center of Huazhong Agricultural University on the 13th–14th of October 2018. It attracted >150 international and local participants, including leading researchers in the field of the 3D genomics and editors from top journals. The main topic of the conference was the research achievements newly published or unpublished on the 3D genome area. The invited speakers shared their works on the topic of the new detection technologies on the 3D genome, the advanced computational analysis algorithms or suites, the nucleus microimaging technique, the simulation modeling method, the application on the biological research in different species (human, animals, plants, microorganisms, etc.) and the applications of 3D genome on medicine and agriculture. The workshop provided a forum to discuss the latest scientific news and ideas from the field of 3D genome research on various aspects of interesting topics.

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22

MacKay, Kimberly y Anthony Kusalik. "Computational methods for predicting 3D genomic organization from high-resolution chromosome conformation capture data". Briefings in Functional Genomics 19, n.º 4 (29 de abril de 2020): 292–308. http://dx.doi.org/10.1093/bfgp/elaa004.

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Abstract The advent of high-resolution chromosome conformation capture assays (such as 5C, Hi-C and Pore-C) has allowed for unprecedented sequence-level investigations into the structure–function relationship of the genome. In order to comprehensively understand this relationship, computational tools are required that utilize data generated from these assays to predict 3D genome organization (the 3D genome reconstruction problem). Many computational tools have been developed that answer this need, but a comprehensive comparison of their underlying algorithmic approaches has not been conducted. This manuscript provides a comprehensive review of the existing computational tools (from November 2006 to September 2019, inclusive) that can be used to predict 3D genome organizations from high-resolution chromosome conformation capture data. Overall, existing tools were found to use a relatively small set of algorithms from one or more of the following categories: dimensionality reduction, graph/network theory, maximum likelihood estimation (MLE) and statistical modeling. Solutions in each category are far from maturity, and the breadth and depth of various algorithmic categories have not been fully explored. While the tools for predicting 3D structure for a genomic region or single chromosome are diverse, there is a general lack of algorithmic diversity among computational tools for predicting the complete 3D genome organization from high-resolution chromosome conformation capture data.

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23

Kim, Yoori y Hongtao Yu. "Shaping of the 3D genome by the ATPase machine cohesin". Experimental & Molecular Medicine 52, n.º 12 (diciembre de 2020): 1891–97. http://dx.doi.org/10.1038/s12276-020-00526-2.

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AbstractThe spatial organization of the genome is critical for fundamental biological processes, including transcription, genome replication, and segregation. Chromatin is compacted and organized with defined patterns and proper dynamics during the cell cycle. Aided by direct visualization and indirect genome reconstruction tools, recent discoveries have advanced our understanding of how interphase chromatin is dynamically folded at the molecular level. Here, we review the current understanding of interphase genome organization with a focus on the major regulator of genome structure, the cohesin complex. We further discuss how cohesin harnesses the energy of ATP hydrolysis to shape the genome by extruding chromatin loops.

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Wang, Maojun, Jianying Li, Pengcheng Wang, Fang Liu, Zhenping Liu, Guannan Zhao, Zhongping Xu et al. "Comparative Genome Analyses Highlight Transposon-Mediated Genome Expansion and the Evolutionary Architecture of 3D Genomic Folding in Cotton". Molecular Biology and Evolution 38, n.º 9 (11 de mayo de 2021): 3621–36. http://dx.doi.org/10.1093/molbev/msab128.

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Abstract Transposable element (TE) amplification has been recognized as a driving force mediating genome size expansion and evolution, but the consequences for shaping 3D genomic architecture remains largely unknown in plants. Here, we report reference-grade genome assemblies for three species of cotton ranging 3-fold in genome size, namely Gossypium rotundifolium (K2), G. arboreum (A2), and G. raimondii (D5), using Oxford Nanopore Technologies. Comparative genome analyses document the details of lineage-specific TE amplification contributing to the large genome size differences (K2, 2.44 Gb; A2, 1.62 Gb; D5, 750.19 Mb) and indicate relatively conserved gene content and synteny relationships among genomes. We found that approximately 17% of syntenic genes exhibit chromatin status change between active (“A”) and inactive (“B”) compartments, and TE amplification was associated with the increase of the proportion of A compartment in gene regions (∼7,000 genes) in K2 and A2 relative to D5. Only 42% of topologically associating domain (TAD) boundaries were conserved among the three genomes. Our data implicate recent amplification of TEs following the formation of lineage-specific TAD boundaries. This study sheds light on the role of transposon-mediated genome expansion in the evolution of higher-order chromatin structure in plants.

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Sun, Xiaoyue, Jing Zhang y Chunwei Cao. "CTCF and Its Partners: Shaper of 3D Genome during Development". Genes 13, n.º 8 (2 de agosto de 2022): 1383. http://dx.doi.org/10.3390/genes13081383.

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The 3D genome organization and its dynamic modulate genome function, playing a pivotal role in cell differentiation and development. CTCF and cohesin, acting as the core architectural components involved in chromatin looping and genome folding, can also recruit other protein or RNA partners to fine-tune genome structure during development. Moreover, systematic screening for partners of CTCF has been performed through high-throughput approaches. In particular, several novel protein and RNA partners, such as BHLHE40, WIZ, MAZ, Aire, MyoD, YY1, ZNF143, and Jpx, have been identified, and these partners are mostly implicated in transcriptional regulation and chromatin remodeling, offering a unique opportunity for dissecting their roles in higher-order chromatin organization by collaborating with CTCF and cohesin. Here, we review the latest advancements with an emphasis on features of CTCF partners and also discuss the specific functions of CTCF-associated complexes in chromatin structure modulation, which may extend our understanding of the functions of higher-order chromatin architecture in developmental processes.

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26

Wang, Juan, Tina Yi-Ting Huang, Ye Hou, Elizabeth Bartom, Xinyan Lu, Ali Shilatifard, Feng Yue y Amanda Saratsis. "Epigenomic landscape and 3D genome structure in pediatric high-grade glioma". Science Advances 7, n.º 23 (junio de 2021): eabg4126. http://dx.doi.org/10.1126/sciadv.abg4126.

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Pediatric high-grade gliomas (pHGGs), including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG), are morbid brain tumors. Even with treatment survival is poor, making pHGG the number one cause of cancer death in children. Up to 80% of DIPGs harbor a somatic missense mutation in genes encoding histone H3. To investigate whether H3K27M is associated with distinct chromatin structure that alters transcription regulation, we generated the first high-resolution Hi-C maps of pHGG cell lines and tumor tissue. By integrating transcriptome (RNA-seq), enhancer landscape (ChIP-seq), genome structure (Hi-C), and chromatin accessibility (ATAC-seq) datasets from H3K27M and wild-type specimens, we identified tumor-specific enhancers and regulatory networks for known oncogenes. We identified genomic structural variations that lead to potential enhancer hijacking and gene coamplification, including A2M, JAG2, and FLRT1. Together, our results imply three-dimensional genome alterations may play a critical role in the pHGG epigenetic landscape and contribute to tumorigenesis.

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Theis, Corinna, Craig L. Zirbel, Christian Höner zu Siederdissen, Christian Anthon, Ivo L. Hofacker, Henrik Nielsen y Jan Gorodkin. "RNA 3D Modules in Genome-Wide Predictions of RNA 2D Structure". PLOS ONE 10, n.º 10 (28 de octubre de 2015): e0139900. http://dx.doi.org/10.1371/journal.pone.0139900.

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28

Varoquaux, N., F. Ay, W. S. Noble y J. P. Vert. "A statistical approach for inferring the 3D structure of the genome". Bioinformatics 30, n.º 12 (15 de junio de 2014): i26—i33. http://dx.doi.org/10.1093/bioinformatics/btu268.

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29

Filion, Guillaume J. y Miguel Beato. "3D genome structure. Organization of the nucleus in space and time". FEBS Letters 589, n.º 20PartA (9 de septiembre de 2015): 2867–68. http://dx.doi.org/10.1016/j.febslet.2015.09.003.

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30

Pombo, Ana. "Specialization of 3D genome structure in different cell types and states". Biophysical Journal 123, n.º 3 (febrero de 2024): 441a. http://dx.doi.org/10.1016/j.bpj.2023.11.2688.

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31

Collins, Brandon, Oluwatosin Oluwadare y Philip Brown. "ChromeBat: A Bio-Inspired Approach to 3D Genome Reconstruction". Genes 12, n.º 11 (3 de noviembre de 2021): 1757. http://dx.doi.org/10.3390/genes12111757.

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With the advent of Next Generation Sequencing and the Hi-C experiment, high quality genome-wide contact data are becoming increasingly available. These 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 (3D-GRP) seeks to take Hi-C data and produces a complete physical genome structure as it appears in the nucleus for genomic analysis. We propose and develop a novel method to solve the Chromosome and Genome Reconstruction problem based on the Bat Algorithm (BA) 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. ChromeBat is an effective approach for solving the Genome Reconstruction Problem.

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32

Torosin, Nicole S., Aparna Anand, Tirupathi Rao Golla, Weihuan Cao y Christopher E. Ellison. "3D genome evolution and reorganization in the Drosophila melanogaster species group". PLOS Genetics 16, n.º 12 (7 de diciembre de 2020): e1009229. http://dx.doi.org/10.1371/journal.pgen.1009229.

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Topologically associating domains, or TADs, are functional units that organize chromosomes into 3D structures of interacting chromatin. TADs play an important role in regulating gene expression by constraining enhancer-promoter contacts and there is evidence that deletion of TAD boundaries leads to aberrant expression of neighboring genes. While the mechanisms of TAD formation have been well-studied, current knowledge on the patterns of TAD evolution across species is limited. Due to the integral role TADs play in gene regulation, their structure and organization is expected to be conserved during evolution. However, more recent research suggests that TAD structures diverge relatively rapidly. We use Hi-C chromosome conformation capture to measure evolutionary conservation of whole TADs and TAD boundary elements between D. melanogaster and D. triauraria, two early-branching species from the melanogaster species group which diverged ∼15 million years ago. We find that the majority of TADs have been reorganized since the common ancestor of D. melanogaster and D. triauraria, via a combination of chromosomal rearrangements and gain/loss of TAD boundaries. TAD reorganization between these two species is associated with a localized effect on gene expression, near the site of disruption. By separating TADs into subtypes based on their chromatin state, we find that different subtypes are evolving under different evolutionary forces. TADs enriched for broadly expressed, transcriptionally active genes are evolving rapidly, potentially due to positive selection, whereas TADs enriched for developmentally-regulated genes remain conserved, presumably due to their importance in restricting gene-regulatory element interactions. These results provide novel insight into the evolutionary dynamics of TADs and help to reconcile contradictory reports related to the evolutionary conservation of TADs and whether changes in TAD structure affect gene expression.

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Chen, Haiming, Jie Chen, Lindsey A. Muir, Scott Ronquist, Walter Meixner, Mats Ljungman, Thomas Ried, Stephen Smale y Indika Rajapakse. "Functional organization of the human 4D Nucleome". Proceedings of the National Academy of Sciences 112, n.º 26 (15 de junio de 2015): 8002–7. http://dx.doi.org/10.1073/pnas.1505822112.

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The 4D organization of the interphase nucleus, or the 4D Nucleome (4DN), reflects a dynamical interaction between 3D genome structure and function and its relationship to phenotype. We present initial analyses of the human 4DN, capturing genome-wide structure using chromosome conformation capture and 3D imaging, and function using RNA-sequencing. We introduce a quantitative index that measures underlying topological stability of a genomic region. Our results show that structural features of genomic regions correlate with function with surprising persistence over time. Furthermore, constructing genome-wide gene-level contact maps aided in identifying gene pairs with high potential for coregulation and colocalization in a manner consistent with expression via transcription factories. We additionally use 2D phase planes to visualize patterns in 4DN data. Finally, we evaluated gene pairs within a circadian gene module using 3D imaging, and found periodicity in the movement of clock circadian regulator and period circadian clock 2 relative to each other that followed a circadian rhythm and entrained with their expression.

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Vadnais, David y Oluwatosin Oluwadare. "ParticleChromo3D+: A Web Server for ParticleChromo3D Algorithm for 3D Chromosome Structure Reconstruction". Current Issues in Molecular Biology 45, n.º 3 (17 de marzo de 2023): 2549–60. http://dx.doi.org/10.3390/cimb45030167.

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Understanding the three-dimensional (3D) structure of chromatin is invaluable for researching how it functions. One way to gather this information is the chromosome conformation capture (3C) technique and its follow-up technique Hi-C. Here, we present ParticleChromo3D+, a containerized web-based genome structure reconstruction server/tool that provides researchers with a portable and accurate tool for analyses. Additionally, ParticleChromo3D+ provides a more user-friendly way to access its capabilities via a graphical user interface (GUI). ParticleChromo3D+ can save time for researchers by increasing the accessibility of genome reconstruction, easing usage pain points, and offloading computational processing/installation time.

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Ikhsan, Fajri, Ahmad Shulhany y Syarif Abdullah. "Metallothionein Protein Modeling from Pseudomonas aeruginosa PAO1 as A Metal Biosorber Candidate". Jurnal Biodjati 8, n.º 2 (28 de noviembre de 2023): 248–61. http://dx.doi.org/10.15575/biodjati.v8i2.29170.

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Metallothionein is a protein that is well known to play a role in metal metabolism in bacterial cells. Metallothionein is a multifunctional protein that has the potential to be used as a metal adsorbing agent. Pseudomonas aeruginosa is a ubiquitous gram-negative and rapid-growth bacterium. In addition, the complete genome of Pseudomonas aeruginosa has been largely known. Pseudomonas aeruginosa PAO1 is a strain of Pseudomonas aeruginosa that the complete genome of this strain is easily accessible in NCBI. These features make Pseudomonas aeruginosa PAO1 become a common model in bacterial studies. This research aimed to find and model the putative metallothionein of Pseudomonas aeruginosa PAO1. This research was carried out by bioinformatic and protein homology methods. Based on the results, the putative metallothionein of Pseudomonas aeruginosa PAO1 was found in the bacterial genome at base sequence of 2355918 to 2356157. The putative metallothionein-encoding gene of Pseudomonas aeruginosa PAO1 has a size of 240 bp. The translation result of the gene showed that the putative metallothionein of Pseudomonas aeruginosa PAO1 has 79 amino acids. The modeling result showed the 3D structure of the putative metallothionein of Pseudomonas aeruginosa PAO1 is similar to the metallothionein 3D structure of Pseudomonas fluorescens Q2-87. The 3D structure of the putative metallothionein of Pseudomonas aeruginosa PAO1 was dominated by turn and coil, but contained 1 α-helix structure and 2 β-sheet structures. Based on protein analysis, it was found that the putative metallothionein of Pseudomonas aeruginosa PAO1 has 1 metal-binding cluster with 10 amino acids and the most important amino acid residue is Cysteine . Even though, there was 1 Histidine amino acid residue on the metal-binding cluster.

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Yamaguchi, A. "Enlarged FAMSBASE: protein 3D structure models of genome sequences for 41 species". Nucleic Acids Research 31, n.º 1 (1 de enero de 2003): 463–68. http://dx.doi.org/10.1093/nar/gkg117.

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Trieu, Tuan, Oluwatosin Oluwadare, Julia Wopata y Jianlin Cheng. "GenomeFlow: a comprehensive graphical tool for modeling and analyzing 3D genome structure". Bioinformatics 35, n.º 8 (12 de septiembre de 2018): 1416–18. http://dx.doi.org/10.1093/bioinformatics/bty802.

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Krijger, Peter Hugo Lodewijk, Bruno Di Stefano, Elzo de Wit, Francesco Limone, Chris van Oevelen, Wouter de Laat y Thomas Graf. "Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming". Cell Stem Cell 18, n.º 5 (mayo de 2016): 597–610. http://dx.doi.org/10.1016/j.stem.2016.01.007.

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Gong, Ke, Harianto Tjong, Xianghong Jasmine Zhou y Frank Alber. "Comparative 3D Genome Structure Analysis of the Fission and the Budding Yeast". PLOS ONE 10, n.º 3 (23 de marzo de 2015): e0119672. http://dx.doi.org/10.1371/journal.pone.0119672.

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Huang, Tina, Juan Wang, Ye Hu, Andrea Piunti, Elizabeth Bartom, Feng Yue y Amanda Saratsis. "EPCO-17. 3D GENOME STRUCTURE REGULATES TRANSCRIPTION IN PEDIATRIC HIGH-GRADE GLIOMA". Neuro-Oncology 25, Supplement_5 (1 de noviembre de 2023): v127. http://dx.doi.org/10.1093/neuonc/noad179.0480.

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Abstract INTRODUCTION Pediatric high-grade gliomas (pHGGs), including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG), are highly morbid brain tumors. Up to 80% of DIPGs harbor a somatic missense mutation in genes encoding Histone H3. To investigate whether the H3K27M mutant protein is associated with distinct chromatin structure affecting transcription regulation, we generated the first high-resolution Hi-C and ATAC-Seq maps of pHGG cell lines, and integrated these with tissue and cell genomic data. METHODS We generated sequencing data from patient-derived cell lines (DIPG n=6, GBM n=3, normal n=2) and frozen tissue specimens (DIPG n=1, normal brainstem n=1). Analyses included cell line RNA-Seq, ChIP-Seq (H3K27ac, H3K27me3, H3K27M) and genome-wide chromatin conformation capture (Hi-C), as well as tissue ATAC-Seq. Publicly available pediatric glioma tissue ChIP-Seq data was integrated with cell data. CRISPR knock-down of target enhancer regions was performed. RESULTS We identified tumor-specific enhancers and regulatory networks for known oncogenes in DIPG and GBM. In DIPG, FOX, SOX, STAT and SMAD families were among top H3K27Ac enriched motifs. Significant differences in Topologically Associating Domains (TADs) and DNA looping were observed at OLIG2 and MYCN in H3K27M mutant DIPG, relative to wild-type GBM and normal cells. Pharmacologic treatment targeting H3K27Ac (BET and Bromodomain inhibition) altered these 3D structures. Functional analysis of differentially enriched enhancers in DIPG implicated SOX2, SUZ12, and TRIM24 as top activated upstream regulators. Distinct genomic structural variations leading to enhancer hijacking and gene co-amplification were identified at A2M, JAG2, and FLRT1. CONCLUSION We show genome structural variations enhancer-promoter interactions that impact gene expression in pHGG in the presence and absence of the H3K27M mutation. Our results imply that tridimensional genome alterations may play a critical role in the pHGG epigenetic landscape and thereby contribute to pediatric gliomagenesis. Further studies examining the impact of the alterations is therefore underway.

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Orozco, Gisela. "Fine mapping with epigenetic information and 3D structure". Seminars in Immunopathology 44, n.º 1 (enero de 2022): 115–25. http://dx.doi.org/10.1007/s00281-021-00906-4.

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AbstractSince 2005, thousands of genome-wide association studies (GWAS) have been published, identifying hundreds of thousands of genetic variants that increase risk of complex traits such as autoimmune diseases. This wealth of data has the potential to improve patient care, through personalized medicine and the identification of novel drug targets. However, the potential of GWAS for clinical translation has not been fully achieved yet, due to the fact that the functional interpretation of risk variants and the identification of causal variants and genes are challenging. The past decade has seen the development of great advances that are facilitating the overcoming of these limitations, by utilizing a plethora of genomics and epigenomics tools to map and characterize regulatory elements and chromatin interactions, which can be used to fine map GWAS loci, and advance our understanding of the biological mechanisms that cause disease.

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Zhou, Jingtian, Jianzhu Ma, Yusi Chen, Chuankai Cheng, Bokan Bao, Jian Peng, Terrence J. Sejnowski, Jesse R. Dixon y Joseph R. Ecker. "Robust single-cell Hi-C clustering by convolution- and random-walk–based imputation". Proceedings of the National Academy of Sciences 116, n.º 28 (24 de junio de 2019): 14011–18. http://dx.doi.org/10.1073/pnas.1901423116.

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Three-dimensional genome structure plays a pivotal role in gene regulation and cellular function. Single-cell analysis of genome architecture has been achieved using imaging and chromatin conformation capture methods such as Hi-C. To study variation in chromosome structure between different cell types, computational approaches are needed that can utilize sparse and heterogeneous single-cell Hi-C data. However, few methods exist that are able to accurately and efficiently cluster such data into constituent cell types. Here, we describe scHiCluster, a single-cell clustering algorithm for Hi-C contact matrices that is based on imputations using linear convolution and random walk. Using both simulated and real single-cell Hi-C data as benchmarks, scHiCluster significantly improves clustering accuracy when applied to low coverage datasets compared with existing methods. After imputation by scHiCluster, topologically associating domain (TAD)-like structures (TLSs) can be identified within single cells, and their consensus boundaries were enriched at the TAD boundaries observed in bulk cell Hi-C samples. In summary, scHiCluster facilitates visualization and comparison of single-cell 3D genomes.

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Belyaeva, Anastasiya, Saradha Venkatachalapathy, Mallika Nagarajan, G. V. Shivashankar y Caroline Uhler. "Network analysis identifies chromosome intermingling regions as regulatory hotspots for transcription". Proceedings of the National Academy of Sciences 114, n.º 52 (11 de diciembre de 2017): 13714–19. http://dx.doi.org/10.1073/pnas.1708028115.

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The 3D structure of the genome plays a key role in regulatory control of the cell. Experimental methods such as high-throughput chromosome conformation capture (Hi-C) have been developed to probe the 3D structure of the genome. However, it remains a challenge to deduce from these data chromosome regions that are colocalized and coregulated. Here, we present an integrative approach that leverages 1D functional genomic features (e.g., epigenetic marks) with 3D interactions from Hi-C data to identify functional interchromosomal interactions. We construct a weighted network with 250-kb genomic regions as nodes and Hi-C interactions as edges, where the edge weights are given by the correlation between 1D genomic features. Individual interacting clusters are determined using weighted correlation clustering on the network. We show that intermingling regions generally fall into either active or inactive clusters based on the enrichment for RNA polymerase II (RNAPII) and H3K9me3, respectively. We show that active clusters are hotspots for transcription factor binding sites. We also validate our predictions experimentally by 3D fluorescence in situ hybridization (FISH) experiments and show that active RNAPII is enriched in predicted active clusters. Our method provides a general quantitative framework that couples 1D genomic features with 3D interactions from Hi-C to probe the guiding principles that link the spatial organization of the genome with regulatory control.

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Iershov, Anton, Konstantin Odynets, Alexander Kornelyuk y Vadim Kavsan. "Homology modeling of 3D structure of human chitinase-like protein CHI3L2". Open Life Sciences 5, n.º 4 (1 de agosto de 2010): 407–20. http://dx.doi.org/10.2478/s11535-010-0039-8.

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AbstractThe human genome encodes six proteins of family 18 glycosyl hydrolases, two active chitinases and four chitinase-like lectins (chi-lectins) lacking catalytic activity. The present article is dedicated to homology modeling of 3D structure of human chitinase 3-like 2 protein (CHI3L2), which is overexpressed in glial brain tumors, and its structural comparison with homologous chi-lectin CHI3L1. Two crystal structures of CHI3L1 in free state (Protein Data Bank codes 1HJX and 1NWR) were used as structural templates for the homology modeling by Modeller 9.7 program, and the best quality model structure was selected from the obtained model ensemble. Analysis of potential oligosaccharide-binding groove structures of CHI3L1 and CHI3L2 revealed significant differences between these two homologous proteins. 8 of 19 amino acid residues important for ligand binding are substituted in CHI3L2: Tyr34/Asp39, Trp69/Lys74, Trp71/Lys76, Trp99/Tyr104, Asn100/Leu105, Met204/Leu210, Tyr206/Phe212 and Arg263/His271. The differences between these residues could influence the structure of the ligand-binding groove and substantially change the ability of CHI3L2 to bind oligosaccharide ligands.

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Chen, Yu, Yang Zhang, Yuchuan Wang, Liguo Zhang, Eva K. Brinkman, Stephen A. Adam, Robert Goldman, Bas van Steensel, Jian Ma y Andrew S. Belmont. "Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler". Journal of Cell Biology 217, n.º 11 (28 de agosto de 2018): 4025–48. http://dx.doi.org/10.1083/jcb.201807108.

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While nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures. In this study, we describe TSA-Seq, a new mapping method capable of providing a “cytological ruler” for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ensemble-averaged results in K562 cells reveal a clear nuclear lamina to speckle axis correlated with a striking spatial gradient in genome activity. This gradient represents a convolution of multiple spatially separated nuclear domains including two types of transcription “hot zones.” Transcription hot zones protruding furthest into the nuclear interior and positioning deterministically very close to nuclear speckles have higher numbers of total genes, the most highly expressed genes, housekeeping genes, genes with low transcriptional pausing, and super-enhancers. Our results demonstrate the capability of TSA-Seq for genome-wide mapping of nuclear structure and suggest a new model for spatial organization of transcription and gene expression.

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Makai, Diána, András Cseh, Adél Sepsi y Szabolcs Makai. "A Multigraph-Based Representation of Hi-C Data". Genes 13, n.º 12 (23 de noviembre de 2022): 2189. http://dx.doi.org/10.3390/genes13122189.

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Chromatin–chromatin interactions and three-dimensional (3D) spatial structures are involved in transcriptional regulation and have a decisive role in DNA replication and repair. To understand how individual genes and their regulatory elements function within the larger genomic context, and how the genome reacts to environmental stimuli, the linear sequence information needs to be interpreted in three-dimensional space, which is still a challenging task. Here, we propose a novel, heuristic approach to represent Hi-C datasets by a whole-genomic pseudo-structure in 3D space. The baseline of our approach is the construction of a multigraph from genomic-sequence data and Hi-C interaction data, then applying a modified force-directed layout algorithm. The resulting layout is a pseudo-structure. While pseudo-structures are not based on direct observation and their details are inherent to settings, surprisingly, they demonstrate interesting, overall similarities of known genome structures of both barley and rice, namely, the Rabl and Rosette-like conformation. It has an exciting potential to be extended by additional omics data (RNA-seq, Chip-seq, etc.), allowing to visualize the dynamics of the pseudo-structures across various tissues or developmental stages. Furthermore, this novel method would make it possible to revisit most Hi-C data accumulated in the public domain in the last decade.

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Stilianoudakis, Spiro C., Maggie A. Marshall y Mikhail G. Dozmorov. "preciseTAD: a transfer learning framework for 3D domain boundary prediction at base-pair resolution". Bioinformatics 38, n.º 3 (6 de noviembre de 2021): 621–30. http://dx.doi.org/10.1093/bioinformatics/btab743.

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Abstract Motivation Chromosome conformation capture technologies (Hi-C) revealed extensive DNA folding into discrete 3D domains, such as Topologically Associating Domains and chromatin loops. The correct binding of CTCF and cohesin at domain boundaries is integral in maintaining the proper structure and function of these 3D domains. 3D domains have been mapped at the resolutions of 1 kilobase and above. However, it has not been possible to define their boundaries at the resolution of boundary-forming proteins. Results To predict domain boundaries at base-pair resolution, we developed preciseTAD, an optimized transfer learning framework trained on high-resolution genome annotation data. In contrast to current TAD/loop callers, preciseTAD-predicted boundaries are strongly supported by experimental evidence. Importantly, this approach can accurately delineate boundaries in cells without Hi-C data. preciseTAD provides a powerful framework to improve our understanding of how genomic regulators are shaping the 3D structure of the genome at base-pair resolution. Availability and implementation preciseTAD is an R/Bioconductor package available at https://bioconductor.org/packages/preciseTAD/. Supplementary information Supplementary data are available at Bioinformatics online.

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Boninsegna, Lorenzo, Asli Yildirim, Guido Polles, Yuxiang Zhan, Sofia A. Quinodoz, Elizabeth H. Finn, Mitchell Guttman, Xianghong Jasmine Zhou y Frank Alber. "Integrative genome modeling platform reveals essentiality of rare contact events in 3D genome organizations". Nature Methods, 11 de julio de 2022. http://dx.doi.org/10.1038/s41592-022-01527-x.

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AbstractA multitude of sequencing-based and microscopy technologies provide the means to unravel the relationship between the three-dimensional organization of genomes and key regulatory processes of genome function. Here, we develop a multimodal data integration approach to produce populations of single-cell genome structures that are highly predictive for nuclear locations of genes and nuclear bodies, local chromatin compaction and spatial segregation of functionally related chromatin. We demonstrate that multimodal data integration can compensate for systematic errors in some of the data and can greatly increase accuracy and coverage of genome structure models. We also show that alternative combinations of different orthogonal data sources can converge to models with similar predictive power. Moreover, our study reveals the key contributions of low-frequency (‘rare’) interchromosomal contacts to accurately predicting the global nuclear architecture, including the positioning of genes and chromosomes. Overall, our results highlight the benefits of multimodal data integration for genome structure analysis, available through the Integrative Genome Modeling software package.

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Wang, Ruiting, Fengling Chen, Qian Chen, Xin Wan, Minglei Shi, Antony K. Chen, Zhao Ma et al. "MyoD is a 3D genome structure organizer for muscle cell identity". Nature Communications 13, n.º 1 (11 de enero de 2022). http://dx.doi.org/10.1038/s41467-021-27865-6.

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AbstractThe genome exists as an organized, three-dimensional (3D) dynamic architecture, and each cell type has a unique 3D genome organization that determines its cell identity. An unresolved question is how cell type-specific 3D genome structures are established during development. Here, we analyzed 3D genome structures in muscle cells from mice lacking the muscle lineage transcription factor (TF), MyoD, versus wild-type mice. We show that MyoD functions as a “genome organizer” that specifies 3D genome architecture unique to muscle cell development, and that H3K27ac is insufficient for the establishment of MyoD-induced chromatin loops in muscle cells. Moreover, we present evidence that other cell lineage-specific TFs might also exert functional roles in orchestrating lineage-specific 3D genome organization during development.

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Vadnais, David, Michael Middleton y Oluwatosin Oluwadare. "ParticleChromo3D: a Particle Swarm Optimization algorithm for chromosome 3D structure prediction from Hi-C data". BioData Mining 15, n.º 1 (21 de septiembre de 2022). http://dx.doi.org/10.1186/s13040-022-00305-x.

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Abstract Background The three-dimensional (3D) structure of chromatin has a massive effect on its function. Because of this, it is desirable to have an understanding of the 3D structural organization of chromatin. To gain greater insight into the spatial organization of chromosomes and genomes and the functions they perform, chromosome conformation capture (3C) techniques, particularly Hi-C, have been developed. The Hi-C technology is widely used and well-known because of its ability to profile interactions for all read pairs in an entire genome. The advent of Hi-C has greatly expanded our understanding of the 3D genome, genome folding, gene regulation and has enabled the development of many 3D chromosome structure reconstruction methods. Results Here, we propose a novel approach for 3D chromosome and genome structure reconstruction from Hi-C data using Particle Swarm Optimization (PSO) approach called ParticleChromo3D. This algorithm begins with a grouping of candidate solution locations for each chromosome bin, according to the particle swarm algorithm, and then iterates its position towards a global best candidate solution. While moving towards the optimal global solution, each candidate solution or particle uses its own local best information and a randomizer to choose its path. Using several metrics to validate our results, we show that ParticleChromo3D produces a robust and rigorous representation of the 3D structure for input Hi-C data. We evaluated our algorithm on simulated and real Hi-C data in this work. Our results show that ParticleChromo3D is more accurate than most of the existing algorithms for 3D structure reconstruction. Conclusions Our results also show that constructed ParticleChromo3D structures are very consistent, hence indicating that it will always arrive at the global solution at every iteration. The source code for ParticleChromo3D, the simulated and real Hi-C datasets, and the models generated for these datasets are available here: https://github.com/OluwadareLab/ParticleChromo3D

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