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• Prostate cancer datasets WGS

  Low pass WGS: 48 samples (5 blood samples from 6 patient data): 22 Tumour cores and 26 normal/benign cores (Next Seq )

  Dataset EGAD00001004466

• Exome-sequencing of human B cell lymphoma cell lines

  26 cell lines derived from human Diffuse Large B Cell lymphomas (DLBCL) or Burkit Lymphomas (BL) were subjected to whole exome sequencing. Exome capture was carried out using the SeqCap EZ Exome Library 2.0 kit (Roche/Nimblegen) and 100 bp single-read sequencing was performed on a HiSeq2500 (Illumina). 82% of the coding region was covered at least 30x.

  Study EGAS00001001463

• Transcriptomic profiling of patient-derived xenografts and organoids in prostate cancer

  Dataset contains RNA-seq of 30 samples (normal prostate tissue, human prostate cancer, PDX and organoids).

  Dataset EGAD00001006404

• The Genetic Landscape of Ocular Adnexa MALT Lymphoma Reveals Frequent Aberrations in NFAT and MEF2B Signaling Pathways

  A comprehensive constellation of somatic non-silent mutations and copy number (CN) variations in ocular adnexa marginal zone lymphoma (OAMZL) is unknown. By utilizing whole-exome sequencing in 69 tumors we define the genetic landscape of OAMZL. Mutations and CN changes in CABIN1 (30%), RHOA (26%), TBL1XR1 (22%), and CREBBP (17%) and inactivation of TNFAIP3 (26%) were among the most common aberrations. Candidate cancer driver genes cluster in the B-cell receptor (BCR), NFkB, NOTCH and NFAT signaling pathways. One of the most commonly altered genes is CABIN1, a calcineurin inhibitor acting as a negative regulator of the NFAT and MEF2B transcriptional activity. CABIN1 deletions enhance BCR-stimulated NFAT and MEF2B transcriptional activity, while CABIN1 mutations enhance only MEF2B transcriptional activity by impairing binding of mSin3a to CABIN1. Our data provide an unbiased identification of genetically altered genes that may play a role in the molecular pathogenesis of OAMZL and serve as therapeutic targets.

  Study EGAS00001006631

• How mitochondrial DNA research can benefit from data reuse through EGA?

  Mitochondria are the only cellular organelles harbouring their own DNA, which encodes for proteins essentials in its respiration process. Despite its discovery in 1960, Mitochondrial DNA is often overlooked compared to nuclear DNA. Indeed, not all sequencing technologies capture a good representation of mtDNA (mitochondrial DNA). Recently, Ed Reznik's team (The Ed Reznik Lab | Memorial Sloan Kettering Cancer Center) carried out a massive analysis and reanalysis of single cells WGS (whole genome sequencing) produced with an amplification-free protocol (Direct library prep, DLP). As they demonstrated in the paper Single-cell mtDNA dynamics in tumors is driven by coregulation of nuclear and mitochondrial genomes - PMC, DLP is more effective in catching mtDNA compared to classical single-cell sequencing. These data allowed the team to unravel mtDNA dynamics in tumoral and normal samples, highlighting how mtDNA and nuclear DNA are co-regulated and their ratio is critical for phenotype. Data reuse to achieve the greatest results For this project, Reznik's team re-used data from 3 studies stored at the European Genome-phenome Archive (EGAS00001006343, EGAS00001004448 and EGAS00001003190) that comprised a total of 602 datasets. All of them were initially produced by the teams of Sam Aparicio and Sohrab P. Shah at the Memorial Sloan Kettering Cancer Centre, where Ed Reznik is a promising group leader. This demonstrates, once again, that networking, collaboration and data sharing can achieve the greatest results when coupled with innovative and smart ideas. At the EGA we are proud to provide the scientific community with an infrastructure to enable all those very smart ideas out there to find the right data to be tested.

  Blog mitochondrial-dna-research

• Single-Cell TCR/BCR Sequencing for Korean COVID-19 Vaccinated and Patient Samples

  We conducted longitudinal single-cell TCR/BCR sequencing for COVID-19 vaccinated cases (297 samples from 112 cases) and COVID-19 infected cases classified as Asymptomatic (26 samples from 12 cases), Mild (82 samples from 37 cases), Moderate (123 samples from 50 cases), Severe (216 samples from 58 cases), and Critical (142 samples from 41 cases) according to the NIH guideline.

  Study phs003341

• Mutational bias in spermatogonia impacts the anatomy of regulatory sites in the human genome

  Mutation in the germline is the ultimate source of genetic variation, but little is known about the influence of germline chromatin structure on mutational processes. Using ATAC-seq, we profile the open chromatin landscape of human spermatogonia, the most proliferative cell-type of the germline, identifying transcription factor binding sites (TFBSs) and PRDM9-binding sites, a subset of which will initiate meiotic recombination. We observe an increase in rare structural variant (SV) breakpoints at PRDM9-bound sites, implicating meiotic recombination in the generation of structural variation. Many germline TFBSs, such as NRF, are also associated with increased rates of SV breakpoints, apparently independent of recombination. Singleton short insertions (>=5 bp) are highly enriched at TFBSs, particularly at sites bound by testis active TFs, and their rates correlate with those of structural variant breakpoints. Short insertions often duplicate the TFBS motif, leading to clustering of motif sites near regulatory regions in this male-driven evolutionary process. Increased mutation loads at germline TFBSs disproportionately affect neural enhancers with activity in spermatogonia, potentially altering neurodevelopmental regulatory architecture. Local chromatin structure in spermatogonia is thus pervasive in shaping both evolution and disease.

  Study EGAS00001005366

• WES dataset of a TIL-ACT metastatic melanoma cohort

  Whole-exome sequencing (WES) data from 13 patients with metastatic melanoma in a TIL-ACT cohort, generated to characterize tumor genomics and neoantigen landscapes relevant to adoptive T cell therapy.

  Dataset EGAD50000001731

• Single-cell RNA sequence analysis of iPS cell-derived cardiomyocytes treated with S-RBD-sfGFP or GFP

  To determine the transcriptional response in human cardiomyocytes treated with SARS-CoV-2 spike receptor-binding domain (S-RBD-sfGFP), human cardiomyocytes differentiated from induced pluripotent stem cells (iPSC-CMs) were replated on day 21 after differentiation and treated with S-RBD-sfGFP or control-GFP for 48 hours on day 26-28. iPSC-CMs were dissociated and the single cell suspension was analyzed by single cell RNA-sequence.

  Study JGAS000620

• Breast Cancer Single-Cell RNA-Seq Dataset

  Single-cell RNA-Sequencing of 26 primary breast cancers from Wu et al. (2021) study. Data was generated using the Chromium controller (10X Genomics) and sequenced on the NextSeq 500 platform.

  Dataset EGAD00001007495