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• Identifying genetic consequences of Epstein-Barr Virus transformation by comparing an individual’s genomic DNA with that of its lymphoblastoid cell line.

  A detailed analysis of whole genomes can be now achieved with next generation sequencing. Epstein Barr Virus (EBV) transformation is a widely used strategy in clinical research to obtain an unlimited source of a subject’s DNA. Although the mechanism of transformation and immortalization by EBV is relatively well known at the transcriptional and proteomic level, the genetic consequences of EBV transformation are less well understood. A detailed analysis of the genetic alterations introduced by EBV transformation is highly relevant, as it will inform on the usefulness and limitations of this approach. We used whole genome sequencing to assess the genomic signature of a low-passage lymphoblastoid cell line (LCL). Specifically, we sequenced the full genome (40X) of an individual using DNA purified from fresh whole blood as well as DNA from his LCL. A total of 217.33 Gb of sequence were generated from the cell line and 238.95 Gb from the normal genomic DNA. We determined with high confidence that 99.2% of the genomes were identical, with no reproducible changes in structural variation (chromosomal rearrangements and copy number variations) or insertion/deletion polymorphisms (indels). Our results suggest that, at this level of resolution, the LCL is genetically indistinguishable from its genomic counterpart and therefore their use in clinical research is not likely to introduce a significant bias.

  Study EGAS00001000323

• Structural variant analysis of homologous recombination-deficient genomes

  Homologous recombination (HR) deficiency causes DNA breaks and cytogenetic aberrations. Paradoxically, the types of DNA rearrangements specifically associated with HR-deficient cancers only minimally impact chromosomal structure. Addressing this, we combined a genome graph analysis of short-read whole genome sequencing (WGS) profiles across thousands of tumors with deep linked-read (LR) WGS of 46 BRCA1 or BRCA2 mutant breast cancers to discover a distinct class of HR deficiency-enriched rearrangements called reciprocal pairs. LR WGS showed that reciprocal pairs with identical rearrangement orientations gave rise to one of two distinct chromosomal outcomes, distinguishable only with long molecule data. While one (cis) outcome corresponded to the copy and pasting of a small segment to a distant site, a second (trans) outcome was a quasi-balanced translocation or multi-megabase inversion with substantial (10kb) duplications at each junction. The full spectrum of reciprocal pair outcomes could be explained by an HR-independent replication restart repair mechanism. LR WGS additionally identified single-strand annealing (SSA) as a BRCA2-deficiency specific repair pathway in human cancers. Replication restart- and SSA-associated SVs improved BRCA1- vs. BRCA2- deficiency classification and identified metastatic cancer cases with favorable chemotherapy responses. Our data reveal classes of BRCA1- and BRCA2-deficiency specific rearrangements as drivers of cytogenetic aberrations in HR deficient cells.

  Study EGAS00001007186

• Sequencing data for oesophageal and related samples - BOs release 2 (RNA)

  Dataset EGAD00001003840

• Transcriptome of human CD4+ T-lymphyocyte (memory-T-cells) treated with Rotenone from donor D3, replicate 2, glucose concentration 5mM

  Dataset EGAD00001008062

• Transcriptome of human CD4+ T-lymphyocyte (memory-T-cells) treated with Oligomycin from donor D2, replicate 2, glucose concentration 5mM

  Dataset EGAD00001008054

• Transcriptome of human CD4+ T-lymphyocyte (memory-T-cells) treated with Oligomycin from donor D2, replicate 2, glucose concentration 1mM

  Dataset EGAD00001008056

• Transcriptome of human CD4+ T-lymphyocyte (memory-T-cells) treated with Resveratrol from donor D3, replicate 2, glucose concentration 5mM

  Dataset EGAD00001008060

• Transcriptome of human CD4+ T-lymphyocyte (memory-T-cells) treated with Oligomycin from donor D3, replicate 2, glucose concentration 5mM

  Dataset EGAD00001008064

• Transcriptome of human CD4+ T-lymphyocyte (memory-T-cells) treated with Oligomycin from donor D3, replicate 2, glucose concentration 1mM

  Dataset EGAD00001008066

• Transcriptome of human CD4+ T-lymphyocyte (naive-T-cells) treated with Resveratrol from donor D1, replicate 2, glucose concentration 5mM

  Dataset EGAD00001008068