Deciphering the role of 3D genome organization in breast cancer susceptibility (RNA-Seq)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA763890 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15914038.fastq.gz | Fastqsanger.gz | |||
| SRR15914039.fastq.gz | Fastqsanger.gz | |||
| SRR15914040.fastq.gz | Fastqsanger.gz | |||
| SRR15914041.fastq.gz | Fastqsanger.gz | |||
| SRR15914042.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 26 |
Similar Datasets
Project description:Deciphering the role of 3D genome organization in breast cancer susceptibility
| PRJNA763885 | ENA
Project description:Deciphering the role of 3D genome organization in breast cancer susceptibility (Hi-C)
| PRJNA763891 | ENA
Project description:Cancer risk by environmental exposure is modulated by an individual’s genetics and age at exposure. This age-specific period of susceptibility is referred to as a “Window of Susceptibility” (WOS). Radiation exposures poses a high breast cancer risk for women between the early childhood and young adult stage and is reduced in the mid-30s. Rats have a similar WOS for developing breast cancer. Previous studies have identified a looping interaction between a genomic region in the mammary carcinoma susceptibility Mcs5c locus and a known cancer gene, PAPPA. However, the global role of three-dimensional organization in the WOS is not known. Therefore, we generated Hi-C and RNA-seq data in rat mammary epithelial cells within and outside WOS. We compared the temporal changes in chromosomal looping to those in expression and find that interactions that have significantly higher counts within WOS are significantly enriched for genes upregulated in WOS. To systematically identify higher-order changes in 3D genome organization, we developed an approach that combines network enhancement to smooth the Hi-C matrices followed by multitask non-negative matrix factorization (NMF) to identify clusters of interacting loci. We found that large-scale topological re-organizations are enriched for differential interactions within and outside the WOS timepoints. Finally, we mapped previously published breast-cancer associated human GWAS variants to rat loci and identified the corresponding rat ortholog gene interacting with the loci. Many of the associated rat genes participate in differential interactions, recapitulate the human SNP- gene interactions and are associated with breast cancer. Our results suggest that WOS-specific changes in 3D genome organization are linked to transcriptional changes that may increase susceptibility to breast cancer.
2022-01-11 | GSE184280 | GEO
Project description:Cancer risk by environmental exposure is modulated by an individual’s genetics and age at exposure. This age-specific period of susceptibility is referred to as a “Window of Susceptibility” (WOS). Radiation exposures poses a high breast cancer risk for women between the early childhood and young adult stage and is reduced in the mid-30s. Rats have a similar WOS for developing breast cancer. Previous studies have identified a looping interaction between a genomic region in the mammary carcinoma susceptibility Mcs5c locus and a known cancer gene, PAPPA. However, the global role of three-dimensional organization in the WOS is not known. Therefore, we generated Hi-C and RNA-seq data in rat mammary epithelial cells within and outside WOS. We compared the temporal changes in chromosomal looping to those in expression and find that interactions that have significantly higher counts within WOS are significantly enriched for genes upregulated in WOS. To systematically identify higher-order changes in 3D genome organization, we developed an approach that combines network enhancement to smooth the Hi-C matrices followed by multitask non-negative matrix factorization (NMF) to identify clusters of interacting loci. We found that large-scale topological re-organizations are enriched for differential interactions within and outside the WOS timepoints. Finally, we mapped previously published breast-cancer associated human GWAS variants to rat loci and identified the corresponding rat ortholog gene interacting with the loci. Many of the associated rat genes participate in differential interactions, recapitulate the human SNP- gene interactions and are associated with breast cancer. Our results suggest that WOS-specific changes in 3D genome organization are linked to transcriptional changes that may increase susceptibility to breast cancer.
2022-01-11 | GSE184284 | GEO
Project description:Cancer risk by environmental exposure is modulated by an individual's genetics and age at exposure. This age-specific period of susceptibility is referred to as the "Window of Susceptibility" (WOS). Rats have a similar WOS for developing breast cancer. A previous study in rat identified an age-specific long-range regulatory interaction for the cancer gene, Pappa, that is associated with breast cancer susceptibility. However, the global role of three-dimensional genome organization and downstream gene expression programs in the WOS is not known. Therefore, we generated Hi-C and RNA-seq data in rat mammary epithelial cells within and outside the WOS. To systematically identify higher-order changes in 3D genome organization, we developed NE-MVNMF that combines network enhancement followed by multitask non-negative matrix factorization. We examined three-dimensional genome organization dynamics at the level of individual loops as well as higher-order domains. Differential chromatin interactions tend to be associated with differentially up-regulated genes with the WOS and recapitulate several human SNP-gene interactions associated with breast cancer susceptibility. Our approach identified genomic blocks of regions with greater overall differences in contact count between the two time points when the cluster assignments change and identified genes and pathways implicated in early carcinogenesis and cancer treatment. Our results suggest that WOS-specific changes in 3D genome organization are linked to transcriptional changes that may influence susceptibility to breast cancer.
| S-EPMC8787344 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-01-11 | GSE184285 | GEO
Project description:The role of the 3D genome organization on platinum drug induced DNA damage susceptibility
| PRJNA1111887 | ENA
Project description:Platinum drugs (Pt drugs) are one of the most widely used chemotherapy drugs in cancer treatment. Although the cytotoxic and resistant mechanisms of Pt drugs have been thoroughly explored, it remains elusive what factors affect the receptiveness of DNA to Pt drug-induced damage. A large fraction of the genome shows significantly altered Pt drug-induced DNA damage susceptibility in the in vivo nuclear environment in comparison to isolated DNA, which cannot be explained only by the transcriptional status and DNA accessibility of the chromatin regions in vivo. Here, we demonstrate that, besides local chromatin structure, the global nuclear locations of genomic regions play a key role in modulating Pt drug-induced DNA damage susceptibility in vivo. By integrating data from damage-seq experiments with 3D genome structure information we show that the preferential nuclear locations of genomic regions relative to specific nuclear bodies and nuclear compartments can explain patterns of Pt drug DNA damage susceptibility. Thus, our observations are consistent with recent in vitro observations of an enrichment of Pt drugs in biomolecular condensates linked to certain nuclear bodies. Finally, when mapping observed DNA damage-seq signals onto 3D genome structures, we found that the 3D nuclear distribution of Pt-drug induced DNA damage differs in drug resistant cells in comparison to drug sensitve cells. In particular DNA damage increases in gene poor chromatin preferentially located in the lamina compartment, while DNA damage is decreased in gene rich regions preferentially located at nuclear speckles. This change may deter Pt-drug induced DNA damage from more viable gene dense chromatin regions that are crucial for short term cell survival. This observation suggests a selective spatial redistribution of Pt drug action in the nucleus during the emergence of chemoresistance. These observations are relevant for a better understanding of Pt drug action and the development of cancer resistant cells.
2025-05-14 | GSE267578 | GEO
Project description:Breast cancer progression entails intricate, multi-level alterations in genome organization and expression. To gain insights into the modifications in chromatin's three-dimensional (3D) structure during breast cancer progression, we conducted an analysis combining Hi-C data with lamina-associated domains (LADs), epigenomic marks, and gene expression in an in vitro model of breast cancer progression. Our results reveal that while the fundamental properties of topologically associating domains (TADs) remain largely stable, significant changes occur in the organization of compartments and subcompartments. These changes are closely correlated with alterations in the expression of oncogenic genes. We also observed a restructuring of TAD-TAD interactions, coinciding with a loss of spatial compartmentalization and radial positioning of the 3D genome. Notably, we identified a previously unrecognized interchromosomal insertion event, wherein a locus on chromosome 8 housing the MYC oncogene becomes inserted into a highly active region on chromosome 10. This insertion event leads to the formation of de novo enhancer contacts and activation of the oncogene, illustrating how structural variants can interact with the 3D genome to drive oncogenic states. In summary, our findings provide evidence for the degradation of genome organization at multiple scales during breast cancer progression revealing the complex interplay between genomic structure and oncogenic processes.
2024-08-07 | GSE246689 | GEO
Project description:Breast cancer progression entails intricate, multi-level alterations in genome organization and expression. To gain insights into the modifications in chromatin's three-dimensional (3D) structure during breast cancer progression, we conducted an analysis combining Hi-C data with lamina-associated domains (LADs), epigenomic marks, and gene expression in an in vitro model of breast cancer progression. Our results reveal that while the fundamental properties of topologically associating domains (TADs) remain largely stable, significant changes occur in the organization of compartments and subcompartments. These changes are closely correlated with alterations in the expression of oncogenic genes. We also observed a restructuring of TAD-TAD interactions, coinciding with a loss of spatial compartmentalization and radial positioning of the 3D genome. Notably, we identified a previously unrecognized interchromosomal insertion event, wherein a locus on chromosome 8 housing the MYC oncogene becomes inserted into a highly active region on chromosome 10. This insertion event leads to the formation of de novo enhancer contacts and activation of the oncogene, illustrating how structural variants can interact with the 3D genome to drive oncogenic states. In summary, our findings provide evidence for the degradation of genome organization at multiple scales during breast cancer progression revealing the complex interplay between genomic structure and oncogenic processes.
2024-08-06 | GSE246947 | GEO