CscoreTool-M infers 3D sub-compartment probabilities within cell population
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PROVIDER: PRJNA930459 | ENA |
REPOSITORIES: ENA
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Project description:Motivation: Computational inference of genome organization based on Hi-C sequencing has greatly aided the understanding of chromatin and nuclear organization in three dimensions (3D). However, existing computational methods fail to address the cell population heterogeneity. Here we describe a probabilistic modeling-based method called CscoreTool-M that infers multiple 3D genome sub-compartments from Hi-C data. Results: The compartment scores inferred using CscoreTool-M represents the probability of a genomic region locating in a specific sub-compartment. Compared to published methods, CscoreTool-M is more accurate in inferring sub-compartments corresponding to both active and repressed chromatin. The compartment scores calculated by CscoreTool-M also help to quantify the levels of heterogeneity in sub-compartment localization within cell populations. By comparing proliferating cells and terminally differentiated non-proliferating cells, we show that the proliferating cells have higher genome organization heterogeneity, which is likely caused by cells at different cell-cycle stages. By analyzing 10 sub-compartments, we found a sub-compartment containing chromatin potentially related to the early-G1 chromatin regions proximal to the nuclear lamina in HCT116 cells, suggesting the method can deconvolve cell cycle stage-specific genome organization among asynchronously dividing cells. Finally, we show that CscoreTool-M can identify sub-compartments that contain genes enriched in housekeeping or cell-type-specific functions. Availability: https://github.com/scoutzxb/CscoreTool-M
2023-05-31 | GSE224282 | GEO
Project description:Large scale changes in coding and non-coding RNA expression is a common feature of the resected hippocampal tissue from pharmacoresistant mesial temporal lobe epilepsy (mTLE) patients. However, there is very less insight on the expression and localization changes of the key regulatory RNAs at a sub-compartment level contributing to pathological mechanisms in mTLE. In the present study we set out to understand the global sub-compartment specific changes in miRNA expression and localization and the alterations in the nucleus that possibly drive these changes and the consequences towards mTLE pathogenesis. We compared the nuclear and cytoplasmic distribution of miRNAs by small RNA-seq in subcellular fractionations of hippocampal tissue from mTLE patients and controls. Several miRNAs were found to be specifically enriched in the nucleus of hippocampal cells from patients compared to the controls, where miR-92b-3p (a miRNA-enriched in neurons) was the most de-regulated nuclear miRNA. By performing miR-92b co-immunoprecipitation (co-IP) assay on N2A nuclei and RNA-seq we identified enrichment of mTLE relevant pathways involving mitochondrial and ribosomal processes.
2024-11-05 | GSE269625 | GEO
Project description:The role of DNA sequence in determining replication timing (RT) and chromatin higher order organization remains elusive. To address this question, we have developed an extra-chromosomal replication system consisting of ~200kb human bacteria artificial chromosomes (BACs) modified with Epstein-Barr virus (EBV) replication origin elements (E-BACs). E-BACs were stably maintained as autonomous mini-chromosomes in both HeLa and human induced pluripotent stem cells (hiPSCs) and established their RT de novo. We applied 4C-seq to evaluate E-BACs' sub-nuclear compartment.
2018-01-29 | GSE102521 | GEO
Project description:Cell and sub-compartment specific proteomics reveals astrocyte contributions in a mouse model of OCD
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Project description:Background: Mutant BRAF targeted therapies remain a standard of care for the treatment of metastatic malignant melanoma (MM); however high initial response rates are tempered by the persistence of residual MM cells that eventually lead to disease recurrence and mortality. Since MM recurrence during targeted therapy can present with the simultaneous occurrence of multiple tumour nodules at the original body sites, we hypothesised the presence of an intrinsically resistant MM cell sub-population. Objectives: Identify an MM cell subpopulation that is intrinsically resistant to targeted therapy and so may be responsible for MM recurrence. Methods: Using melanoma cell lines, we define culture conditions for reproducible 3D growth of melanospheres to investigate putative cancer stem cell populations. We undertook RNA sequencing and bioinformatic analysis to characterise cell populations between adherent and non-adherent culture, and cells expressing or not expressing CD20. Furthermore, we define an in vitro assay to evaluate killing of melanoma cancer stem cells as a therapeutic test using combination therapies targeting driver mutation and CD20 marker. Results: We have described culture conditions that promote MM cells to form melanospheres with a reproducible colony forming efficiency of 0.3% to 1.3%. RNA sequencing of melanosphere versus conventional MM cell cultures (n=6), irrespective of the BRAF mutation status, showed that melanosphere formation was associated with growth and differentiation transcriptional signatures resembling MM tumours. Importantly, melanosphere formation also led to the emergence of a CD20+ MM cell subpopulation, similar to that observed in primary human MM tumours. CD20+ MM cells were resistant to BRAF inhibitor therapy, and consistent with this finding demonstrated a Forkhead box protein M1 (FOXM1) transcriptomic profile (n=6). Combining BRAF inhibitor and anti-CD20 antibody treatment led to the additional killing of previously resistant CD20+ BRAF mutant MM cells. Conclusions: In MM patients that harbour a CD20+ sub-population, combined therapy with BRAF inhibitor and anti-CD20 antibody could potentially kill residual MM cells and so prevent disease recurrence.
2024-02-22 | GSE248906 | GEO
Project description:X chromosome dosage compensation in Drosophila requires chromosome-wide coordination of gene activation. The male-specific-lethal dosage compensation complex (DCC) identifies X chromosomal High Affinity Sites (HAS) from which it reaches out to boost transcription. A recently discovered sub-class of HAS, PionX sites, represent first contacts on the X. We explored the chromosomal interactions of representative PionX sites by high-resolution 4C methodology and determined the overall chromosome conformation by Hi-C in sex-sorted embryos. X chromosomes from male and female cells display similar nuclear architecture, concordant with clustered, constitutively active genes. PionX sites, like HAS, are evenly distributed in the active compartment and engage in short- and long-range interactions beyond compartment boundaries. De novo induction of DCC in female cells allowed monitoring the reach of activation surrounding PionX sites. Remarkably, DCC not only activates genes in linear proximity, but also at megabase distance if close in space, suggesting that dosage compensation profits from chromosome folding.
2017-07-01 | GSE94115 | GEO
Project description:Bacterial artificial chromosomes establish replication timing and sub-nuclear compartment de novo as extra-chromosomal vectors
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Project description:Bacterial artificial chromosomes establish replication timing and sub-nuclear compartment de novo as extra-chromosomal vectors
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Project description:The mouse bone marrow cell line FDCPmix was fractionated on the basis of surface detection of c-Kit, Sca-1, and Gr1 antigens. Four compartments were profiled Gr1+ cells (myeloid-committed compartment = MCP); kit-Gr1- cells (erythroid-committed compartment = ECP); kit+Gr1- cells (self-renewing cells = SR) further sub-divided as the lowest and highest 20% of Sca-1 expression (SR Sca1-lo and SR Sca1-hi, respectively). Bulk (unfractionated) FDCPmix cells were included as controls.
2017-02-10 | GSE68754 | GEO
Project description:Sub-compartment specific small non-coding RNA expression deregulation and altered nucleoli in mesial temporal lobe epilepsy
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