Ontology highlight
ABSTRACT:
PROVIDER: PRJNA971876 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24520120_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Structural variations (SVs) contribute significantly to the variability of the human genome and extensive genomic rearrangements are a hallmark of cancer. Genomic DNA paired-end-tag (DNA-PET) sequencing is an attractive approach to identify genomic SVs. The current application of PET sequencing with short insert size DNA is insufficient for the comprehensive mapping of SVs in low complexity and repeat-rich genomic regions. We have developed a robust procedure to generate PET sequencing data using large DNA inserts of 10 - 20 kb for the identification of SVs. We compared the characteristics of the large insert libraries with short insert (1 kb) libraries with the same sequencing depths and costs. Although short insert libraries bear an advantage in identifying small deletions, they do not provide a significantly better breakpoint resolution. Large inserts are superior to short inserts in providing higher physical genome coverage and therefore achieve greater sensitivity for the identification of the different types of SVs, including copy number neutral and complex events. Further, large inserts allow the identification of SVs within repetitive sequences which cannot be spanned by short inserts. Structural variations of three cancer cell lines using short (1 kb) and long (10 kb and 20 kb) insert size DNA fragments
2012-10-04 | E-GEOD-32674 | biostudies-arrayexpress
Project description:Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long span paired-end-tag (PET) sequencing approach using 10 Kb genomic DNA inserts to study human genome structural variations (SVs). The use of 10 Kb insert size allows the identification of breakpoints within repetitive or homology containing regions of a few Kb in size and results in a higher physical coverage compared to small insert libraries with the same sequencing effort. We have applied this approach to comprehensively characterize the SVs of 15 cancer and 2 non-cancer genomes and used a filtering approach to strongly enrich for somatic SVs in the cancer genomes. Our analyses revealed that most inversions, deletions, and insertions are germline SVs, whereas tandem duplications, unpaired inversions, inter-chromosomal translocations, and complex rearrangements are overrepresented among somatic rearrangements in cancer genomes. We demonstrate that the quantitative and connective nature of DNA-PET data is precise in delineating the genealogy of complex rearrangement events, we observe signatures which are compatible with breakage-fusion-bridge cycles, and discover that large duplications are among the initial rearrangements that trigger genome instability for extensive amplification in epithelial cancers. Structural variations of 15 human cancer samples and 2 human normal samples were identified by long span paired-end sequencing
2011-04-06 | E-GEOD-26954 | biostudies-arrayexpress
Project description:Glioblastoma multiforme is the most common and aggressive type of brain cancer. Little is known about the complex relationship between genomic and epigenomic as tumour progresses. We present the following base resolution whole genome maps of matched tumour/margin and blood samples from a glioblastoma multiforme patient:<br>* Single nucleotide variations (SNVs), copy number variations (CNVs) and structural variations (SVs) as revealed by DNA sequencing. </br> <br>* 5-methylcytosine and 5-hydroxymethylcytosine levels obtained using (oxidative)bisulfite sequencing. </br> <br>* Transcript levels produced using RNA sequencing.</br> <br>For the three samples with very large bam raw data files ('Blood DNA-seq', 'Margin DNA-seq' and 'Tumour DNA-seq'), bai index files are available from https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-5171/E-MTAB-5171.additional.1.zip
2017-02-24 | E-MTAB-5171 | biostudies-arrayexpress
Project description:Structural variations (SVs) contribute significantly to the variability of the human genome and extensive genomic rearrangements are a hallmark of cancer. Genomic DNA paired-end-tag (DNA-PET) sequencing is an attractive approach to identify genomic SVs. The current application of PET sequencing with short insert size DNA is insufficient for the comprehensive mapping of SVs in low complexity and repeat-rich genomic regions. We have developed a robust procedure to generate PET sequencing data using large DNA inserts of 10 - 20 kb for the identification of SVs. We compared the characteristics of the large insert libraries with short insert (1 kb) libraries with the same sequencing depths and costs. Although short insert libraries bear an advantage in identifying small deletions, they do not provide a significantly better breakpoint resolution. Large inserts are superior to short inserts in providing higher physical genome coverage and therefore achieve greater sensitivity for the identification of the different types of SVs, including copy number neutral and complex events. Further, large inserts allow the identification of SVs within repetitive sequences which cannot be spanned by short inserts.
2012-10-04 | GSE32674 | GEO
Project description:Background The safety of CRISPR-based gene editing methods is of the utmost priority in clinical applications. Previous studies have reported that Cas9 cleavage induced frequent aneuploidy in primary human T cells, but whether cleavage-mediated editing of base editors would generate off-target structure variations remains unknown. Here, we investigated the potential off-target structural variations associated with CRISPR/Cas9, ABE and CBE editing in mouse embryos and primary human T cells by whole-genome sequencing and single-cell RNA-seq analyses. Results The results showed that both Cas9 and ABE generated off-target structural variations (SVs) in mouse embryos, while CBE induced rare SVs. In addition, off-target large deletions were detected in 32.74% of primary human T cells transfected with Cas9 and 9.17% of cells transfected with ABE. Moreover, Cas9-induced aneuploid cells activated the P53 and apoptosis pathways, whereas ABE-associated aneuploid cells significantly upregulated cell cycle-related genes and arrested in G0 phase. A percentage of 16.59% and 4.29% aneuploid cells were still observable at 3 weeks post transfection of Cas9 or ABE. These off-target phenomena in ABE were universal as observed in other cell types such as B cells and Huh7. Furthermore, the off-target SVs were significantly reduced in cells treated with high-fidelity ABE (ABE-V106W). Conclusions This study raises urgent need for minimizing the off-target SVs of CRISPR/Cas9 and ABE.
2024-11-01 | GSE280767 | GEO
Project description:Whole-genome tiling arrays were used to validate deletions and tandem duplications that were inferred based on next-generation sequencing data. The arrays were generated for six samples of the Drosophila melanogaster Genetic Reference Panel (DGRP) as well as the Berkeley reference strain. Structural variations (SVs) were assessed by comparing probe intensities within the region of interest between the sample for which the SV was predicted and the reference strain.
2012-11-29 | E-MTAB-1105 | biostudies-arrayexpress
Project description:CRISPR/Cas9 has been adapted to disrupt endogenous genes in adoptive T-lymphocyte therapy to prevent graft-versus-host disease. However, genome editing also generates prevalent deleterious structural variations (SVs), including chromosomal translocations and large deletions, raising safety concerns about reinfused T cells. Here, we dynamically monitored the progression of SVs in a mouse model of T-cell receptor (TCR)-transgenic T-cell adoptive transfer, mimicking TCR T therapeutics. Remarkably, CRISPR/Cas9-induced SVs persist and undergo clonal expansion in vivo after three weeks or even two months, evidenced by high enrichment and low junctional diversity of identified SVs post infusion. Specifically, we detected 128 expanded translocations, with 20,615 as the highest number of amplicons. The identified SVs are stochastically selected among different individuals and show an inconspicuous locus preference. Moreover, viral DNA integrations are routinely detected in edited T cells and also undergo clonal expansion as SVs do. The persistent SVs and viral DNA integrations in the infused T cells may constantly threaten genome integrity, drawing immediate attention to the safety of CRISPR/Cas9-engineered T cells mediated immunotherapy.
2022-10-12 | GSE202887 | GEO
Project description:Many environmental, genetic, and epigenetic factors are known to affect the frequency and positioning of meiotic crossovers (COs). Suppression of COs by large, cytologically visible inversions and translocations has long been recognized, but relatively little is known about how smaller structural variants (SVs) affect COs. To examine fine-scale determinants of the CO landscape, including SVs, we used a rapid, cost-effective method for high-throughput sequencing to generate a precise map of over 17,000 COs between the Col-0 and Ler accessions of Arabidopsis thaliana. COs were generally suppressed in regions with SVs, but this effect did not depend on the size of the variant region, and was only marginally affected by the variant type. CO suppression did not extend far beyond the SV borders, and CO rates were slightly elevated in the flanking regions. Disease resistance gene clusters, which often exist as SVs, exhibited high CO rates at some loci, but there was a tendency toward depressed CO rates at loci where large structural differences exist between the two parents. Our high-density map also revealed in fine detail how CO positioning relates to genetic (DNA motifs) and epigenetic (chromatin structure) features of the genome. We conclude that suppression of COs occurs over a narrow region spanning large and small-scale SVs, representing influence on the CO landscape in addition to sequence and epigenetic variation along chromosomes.
2019-08-25 | E-MTAB-8165 | biostudies-arrayexpress
Project description:Rapeseed (Brassica napus L.) is a globally significant oil-producing crop, and its structural variations (SVs) are fundamental to the enhancement and domestication of important agronomic traits. However, the effects of SVs on agronomic traits in allotetraploid rapeseed are still largely unexplored. Here, we conducted a whole-genome identification of SVs based on 300 re-sequenced rapeseed accessions and found 42,384 high-quality SVs consisted of 34,442 deletions, 6,653 insertions, 828 duplications and 461 inversions. Onset of inflorescence formation and subsequent flower opening at the proper time is crucial for successful propagation. To uncover significant SVs associated with inflorescence development, we performed genome-wide association study based on SVs (SV-GWAS) and identified seven significant SVs. Through analysis of each SV and referencing previous studies, we explored the SV in the second intron of LEAFY on Chromosome C3 (BnaC3.LFY), which is one of homologs of Arabidopsis floral identification gene LFY (AtLFY). BnaC3.LFY Hap1 is significantly related to early inflorescence development due to increased gene expression of BnaC3.LFY. By the CRISPR/Cas9 application in the wild-type spring accession Westar, multiple deletions in intron 2 region of BnaC3.LFY were received and the phenotype of delayed flowering opening was observed. Additionally, we discovered the conserved function of the second intron in Arabidopsis. This study demonstrates the whole-genome layout of SVs in Brassica napus genomes and highlights the conserved role of the second intron of BnaC3.LFY in influencing the timing of inflorescence formation and flower opening, with significant agronomic implications.
2025-06-25 | GSE285927 | GEO
Project description:We identified genomic structural alterations of six patients with signs of neurodevelopmental disorder (NDDs) that harbour chromosomal rearrangements using large-insert paired-end tag sequencing (DNA-PET). This technique allowed the refinement of chromosomal breakpoints and lead to the identification of seven disrupted genes (GNAQ, RBFOX3, UNC5D, TMEM47, NCAPG2, GTDC1 and XIAP). For one patient we filtered the entire panel of structural variations (SVs) with his parents and identified a unique SV that disrupted a single gene: GTDC1. We then validated the functional consequences of the chromosomal breakpoint disruption of GTDC1 by using patient-derived iPSCs. By differentiating these cells into neural progenitor cells (NPCs) and neurons, we interrogated the disease process at the cellular level and observed defects in the proliferation and glycosylation status of NPCs and also defects in neuronal maturation and function. We compared these results with GTDC1-deficient wild-type human NPCs and neurons, and observed similar phenotypic features as in the patient-derived cells which confirm that GTDC1 is involved in the patient’s phenotype. We show here that the combination of genomic screening with iPSCs technology provides a mechanistic insight into possible contributory effects of candidate genes implicated in NDDs and for personalized medicine. Structural variations were identified by long insert DNA paired-end tag (DNA-PET) sequencing, a mate-pair sequencing approach.
2014-09-03 | E-GEOD-51430 | biostudies-arrayexpress