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• Benchmarking of ProSolo, a new probabilistic single nucleotide variant caller for single cell DNA sequencing data. This study provides the whole exome sequencing dataset used in this assessment.

  Benchmarking of ProSolo, a new probabilistic single nucleotide variant caller for single cell DNA sequencing data that provides control over the false discovery rate of different single cell events at genomic sites (e.g. alternative allele presence or allele dropout). Here, we provide the newly generated whole exome sequencing data used in assessing ProSolo's performance. It contains whole exome sequencing of: a patient with a constitutional mismatch repair defect (MSH6-) and their parents and siblings, a granulocyte bulk sample and 5 single granulocytes sequenced after whole genome amplification.

  Study EGAS00001004123

• Duplex sequencing of 26 genes

  Buccal samples and paired esophageal epithelium were obtained using the three sizes of swabs and endoscopic biopsy, respectively. Forty samples from 10 subjects were analyzed via duplex sequencing. This dataset contains bam files that were mapped to the GRCh37 reference genome.

  Dataset EGAD50000000998

• WGS

  Whole Genome Sequencing

  Dataset EGAD00001001120

• PROMETEO

  The SOLTI-1503 PROMETEO trial was a single-arm, preoperative, window-of-opportunity phase II study conducted at four sites in Spain between December 2018 and February 2022. It enrolled female patients with operable HER2-negative breast cancer (triple-negative or Luminal B-like) and residual disease after neoadjuvant chemotherapy. Tumor biopsies were collected at five time points (baseline, post-NAC screening, C2D1, C3D1, and surgery) for translational research. This dataset includes raw paired-end RNA sequencing data (~110M reads per library) generated from the 113 biopy samples, archived in FASTQ format.

  Study EGAS50000001499

• Methylation Biomarkers can Distinguish Pleural Mesothelioma from Healthy Pleura and other Pleural Pathologies

  Pleural mesothelioma (PM) is a rare cancer type. This study developed a methylation-based biomarker assay to distinguish PM from healthy pleura and other pleural conditions. By analyzing methylation data, 744 hypermethylated CpG sites specific to PM were identified and validated with high accuracy. Using the bisulfite-free IMPRESS technique, the assay was further validated in a diverse cohort, showing strong performance in distinguishing tumoral from non-tumoral samples and PM from pleural metastases. These findings support the assay’s potential as a robust diagnostic tool for PM.

  Study EGAS00001008153

• Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma

  Background:Malignant pleural mesothelioma (MPM) is a heterogeneous cancer. Better knowledge of molecular and cellular intra-tumor heterogeneity throughout the thoracic cavity is required to develop efficient therapies. This study focuses on molecular intra-tumor heterogeneity using the largest series to date in MPM and is the first to report on the multi-omics profiling of a substantial series of multi-site tumor samples. Methods:Intra-tumor heterogeneity was investigated in 16 patients from whom biopsies were taken at distinct anatomical sites. The paired biopsies collected from apex, side wall, costo-diaphragmatic or highest metabolic sites as well as 5 derived cell lines were screened using targeted sequencing. Whole exome sequencing, RNA sequencing, and DNA methylation were performed on a subset of the cohort for deep characterization. Molecular classification, recently defined histo-molecular gradients, and cell populations of the tumor microenvironment were assessed. Results:Sequencing analysis identified heterogeneous variants notably in NF2, a key tumor suppressor gene of mesothelial carcinogenesis. Subclonal tumor populations were shared among paired biopsies, suggesting a polyclonal dissemination of the tumor. Transcriptome analysis highlighted dysregulation of cell adhesion and extracellular matrix pathways, linked to changes in histo-molecular gradient proportions between anatomic sites. Methylome analysis revealed contribution of epigenetic mechanisms in two patients. Finally, significant changes in the expression of immune mediators and genes related to immunological synapse, as well as differential infiltration of immune populations in the tumor environment were observed and led to a switch from a hot to a cold immune profile in three patients. Conclusions:This comprehensive analysis reveals patient-dependent spatial intra-tumor heterogeneity at the genetic, transcriptomic and epigenetic levels and in the immune landscape of the tumor microenvironment. Results support

  Study EGAS00001005328

• Center for Common Disease Genomics [CCDG] - Autoimmune: Inflammatory Bowel Disease (IBD) Exomes and Genomes

  The National Human Genome Research Institute (NHGRI) has funded a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes. Called the Centers for Common Disease Genomics (CCDG), this initiative will explore a range of diseases with the ultimate goal of: undertaking variant discovery for enough different examples of disease architectures and study designs to better understand the general principles of the genomic architecture underlying common, complex inherited diseases; understanding how best to design rare variant studies for common disease; developing resources, informatics tools, and innovative approaches and technologies for multiple disease research communities and the wider biomedical research community. The initial focus of the CCDGs will be in cardiovascular disease (early-onset coronary artery disease, atrial fibrillation, hemorrhagic stroke), neuropsychiatric disease (epilepsy, autism), and autoimmune/inflammatory disease (type 1 diabetes, inflammatory bowel disease). The Broad Institute is one of four selected CCDG project centers. The overarching aim of the Inflammatory Bowel Disease (IBD) program is to define the full allelic spectrum of protein-altering variation in genes associated to IBD, and assess their role in both Crohn's Disease (CD) and Ulcerative Colitis (UC) risk. The whole genome sequencing data generated here is comprised of samples from US-based diverse populations including African American, Puerto-Rican, Caribean and Cuban origins.

  Study phs001642

• Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS)

  Advances in antiretroviral therapies (ART) and patient management have improved survival of people living with HIV (PLWH). However, with exposure to ART and associated side effects and toxicities as well as to the virus itself, PLWH are at an increased risk of several chronic diseases. The Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) research network integrates longitudinal clinical data and treatment management of PLWH and provides research infrastructure to support HIV-associated clinical, social, and behavioral outcomes and comparative effectiveness research using data collected from 8 Centers for AIDS Research clinical sites across United States. For detailed study description, see Kitahata et al. (2008, PMID:18263650).

  Study phs001788

• Small‑scale mutations are infrequent as mechanisms of resistance in post‑PARP inhibitor tumour samples in high grade serous ovarian cancer

  Targeted DNA sequencing of high-grade serous ovarian cancer (HGSC) tumour and normal samples from 26 patients. Following target hybrid capture of 63 genes involved in DNA repair and response to treatment with an Agilent SureSelect XT panel, sequencing libraries were generated using the SureSelect XT Low Input Target Enrichment System (Agilent) as per the manufacturer's protocol. Libraries were sequenced on an Illumina NextSeq 500 at the Peter MacCallum Cancer Centre (Melbourne, Australia).

  Study EGAS50000000146

• Harnessing_transposons_for_drug_resistance_gene_discovery_in_cancer

  This study involves a forward genetic screen to identify common insertion sites in drug resistant clones. We will be utilising piggybac transposon systems in order to generate multiple drug resistant clones in a range of human cancer cell lines.

  Study EGAS00001000468