3D-GNOME 2.0: a three-dimensional genome modeling engine for predicting structural variation-driven alterations of chromatin spatial structure in the human genome

Wlasnowolski, Michał; Sadowski, Michal; Czarnota, Tymon; Jodkowska, Karolina; Szałaj, Przemysław; Tang, Zhonghui; Ruan, Yijun; Plewczynski, Dariusz

doi:10.1093/nar/gkaa388

Cited by 22 publications

(13 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides, SVs have a more direct impact on the three-dimensional (3D) genome than SNVs [ 40 ]. Using a recently published algorithm [ 40 , 41 ], we found that four Tibetan-Han stratified SVs could lead to chromatin conformational changes (“ Methods ” section; Fig. 4 C).…”

Section: Resultsmentioning

confidence: 99%

Characterization of structural variation in Tibetans reveals new evidence of high-altitude adaptation and introgression

Cheng

Liu

et al. 2021

Genome Biol

View full text Add to dashboard Cite

Background Structural variation (SV) acts as an essential mutational force shaping the evolution and function of the human genome. However, few studies have examined the role of SVs in high-altitude adaptation and little is known of adaptive introgressed SVs in Tibetans so far. Results Here, we generate a comprehensive catalog of SVs in a Chinese Tibetan (n = 15) and Han (n = 10) population using nanopore sequencing technology. Among a total of 38,216 unique SVs in the catalog, 27% are sequence-resolved for the first time. We systematically assess the distribution of these SVs across repeat sequences and functional genomic regions. Through genotyping in additional 276 genomes, we identify 69 Tibetan-Han stratified SVs and 80 candidate adaptive genes. We also discover a few adaptive introgressed SV candidates and provide evidence for a deletion of 335 base pairs at 1p36.32. Conclusions Overall, our results highlight the important role of SVs in the evolutionary processes of Tibetans’ adaptation to the Qinghai-Tibet Plateau and provide a valuable resource for future high-altitude adaptation studies.

show abstract

Section: Resultsmentioning

confidence: 99%

Characterization of structural variation in Tibetans reveals new evidence of high-altitude adaptation and introgression

Cheng

Liu

et al. 2021

Genome Biol

View full text Add to dashboard Cite

show abstract

“…Besides the prediction of the overall rearrangement effect, it is possible to predict changes in 3-D genome structures as TADs and loops. The 3D-GNOME algorithm (Sadowski et al, 2019;Wlasnowolski et al, 2020) generates chromatin 3-D structures using a Monte Carlo approach based on chromatin conformation capture (3C) data. It uses high-quality CTCF or RNA polymerase II ChIA-PET data as a reference chromatin interaction pattern.…”

Section: Prediction Of Functional Consequences Of Rearrangementsmentioning

confidence: 99%

Predicting Genome Architecture: Challenges and Solutions

Belokopytova

Fishman

2021

Front. Genet.

View full text Add to dashboard Cite

Genome architecture plays a pivotal role in gene regulation. The use of high-throughput methods for chromatin profiling and 3-D interaction mapping provide rich experimental data sets describing genome organization and dynamics. These data challenge development of new models and algorithms connecting genome architecture with epigenetic marks. In this review, we describe how chromatin architecture could be reconstructed from epigenetic data using biophysical or statistical approaches. We discuss the applicability and limitations of these methods for understanding the mechanisms of chromatin organization. We also highlight the emergence of new predictive approaches for scoring effects of structural variations in human cells.

show abstract

“…To assess if modular-territories in the regulatory network are representations of structure-based domains such as TADs and chromatin contact domains (CCDs), we investigated global and local CTCF-mediated 3D reconstruction (fig. S13A-B) (51,52). Locally, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) and CTCF-mediated reconstruction from several cell lines (51) revealed a clear overlap between CTCF-cluster graphs and network submodule territories (fig.…”

Section: S9a-b and Tablementioning

confidence: 99%

Metabolic resilience is encoded in genome plasticity

Agudelo

Tuyéras

Llinares

et al. 2021

Preprint

View full text Add to dashboard Cite

Metabolism plays a central role in evolution, as resource conservation is a selective pressure for fitness and survival. Resource-driven adaptations offer a good model to study evolutionary innovation more broadly. It remains unknown how resource-driven optimization of genome function integrates chromatin architecture with transcriptional phase transitions. Here we show that tuning of genome architecture and heterotypic transcriptional condensates mediate resilience to nutrient limitation. Network genomic integration of phenotypic, structural, and functional relationships reveals that fat tissue promotes organismal adaptations through metabolic acceleration chromatin domains and heterotypic PGC1A condensates. We find evolutionary innovation in several dimensions; low conservation of amino acid residues within protein disorder regions, nonrandom chromatin location of metabolic acceleration domains, condensate-chromatin stability through cis-regulatory archoring and encoding of genome plasticity in radial chromatin organization. We show that environmental tuning of these adaptations leads to fasting endurance, through efficient nuclear compartmentalization of lipid metabolic regions, and, locally, human-specific burst kinetics of lipid cycling genes. This process reduces oxidative stress, and fatty-acid mediated cellular acidification, enabling endurance of condensate chromatin conformations. Comparative genomics of genetic and diet perturbations reveal mammalian convergence of phenotype and structural relationships, along with loss of transcriptional control by diet-induced obesity. Further, we find that radial transcriptional organization is encoded in functional divergence of metabolic disease variant-hubs, heterotypic condensate composition, and evolutionary tuned protein residues sensing metabolic variation. During fuel restriction, these features license the formation of large heterotypic condensates that buffer proton excess, and shift viscoelasticity for condensate endurance. This mechanism maintains physiological pH, reduces pH-resilient inflammatory gene programs, and enables genome plasticity through transcriptionally driven cell-specific chromatin contacts. In vivo manipulation of this circuit promotes fasting-like adaptations with heterotypic nuclear compartments, metabolic and cell-specific homeostasis. In sum, we uncover here a general principle by which transcription uses environmental fluctuations for genome function, and demonstrate how resource conservation optimizes transcriptional self-organization through robust feedback integrators, highlighting obesity as an inhibitor of genome plasticity relevant for many diseases.

show abstract

3D-GNOME 2.0: a three-dimensional genome modeling engine for predicting structural variation-driven alterations of chromatin spatial structure in the human genome

Cited by 22 publications

References 19 publications

Characterization of structural variation in Tibetans reveals new evidence of high-altitude adaptation and introgression

Characterization of structural variation in Tibetans reveals new evidence of high-altitude adaptation and introgression

Predicting Genome Architecture: Challenges and Solutions

Metabolic resilience is encoded in genome plasticity

Contact Info

Product

Resources

About