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• My Pediatric and Adult Rare Tumor (MyPART) Natural History Study of Rare Solid Tumors

  The goal of this study is to comprehensively and longitudinally evaluate the natural history of patients with rare solid tumors or tumor predisposition syndromes, estimating and defining their clinical spectrum (e.g. disease course and survival). Clinical data, patient reported outcomes (PROs), and biospecimen associated data are collected. Clinical data includes response to treatment, tumor pathology, and imaging. PROs include measures of pain, depression, anxiety, mobility, and cognitive functioning. Biospecimen data includes next-generation sequencing [RNAseq, whole exome sequencing (WES), whole genome sequencing (WGS), EPIC methylation array data, and TruSight Oncology 500 gene panel sequencing], cytokine analysis of plasma, immune phenotyping of circulating peripheral blood mononuclear cells.

  Study phs003143

• Primary central nervous system lymphoma (PCNSL) biopsies show heterogeneity in gene expression profiles, genetic subtypes, and in vitro drug sensitivity to kinase inhibitors

  Primary central nervous system lymphoma (PCNSL) is an aggressive large B-cell lymphoma, most often of the activated B cell (ABC) subtype, but with limited tumor biology studies due to small biopsy size and lack of strict cohort definition. Here we examined the genetic heterogeneity of 29 HIV- EBV- PCNSL tumors using whole exome sequencing (WES). We compared these tumors to 5 cell lines comprised of two human PCNSL cell lines (TK and HKBML) and three systemic activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) (OCI-Ly3, TMD-8, HBL-1).

  Study EGAS50000000312

• A Study to Evaluate Denosumab in Young Patients With Primary Breast Cancer (D-Beyond)

  This is a prospective, single arm phase IIa trial in which patients with early breast cancer will receive pre-operatively two doses of denosumab 120mg subcutaneously one week apart (maximum 12 days) followed by surgery. Tumor, normal breast tissue and blood samples will be collected at baseline and at surgery. Post-operative treatment will be at the discretion of the investigator.Primary objective: to determine if a short course of RANKL inhibition with denosumab can induce a decrease in tumor proliferation rates as determined by Ki67 immunohistochemistry (IHC) in newly diagnosed, early stage breast cancer in pre-menopausal women.

  Study EGAS00001003252

• Oligodendroglia as functional effectors of Multiple Sclerosis risk variants (iPS derived hOPC scCRISPRi/a-seq)

  Study of the regulatory effect of a selection Multiple Sclerosis (MS) associated SNPs applying high-throughput functional genomics in human induced pluripotent stem cell-derived oligodendroglia (iPS-derived hOPCs). Selected cis-regulatory elements were assesed with lentiviral-based pooled single cell (sc)CRISPR-seq screens. CRISPRi/a (dCas9-KRAB and dCas9-p300 respectively) was performed, in combination with direct-capture Perturb-sequencing single-guide RNA (sgRNA) and droplet-based single-cell RNA-seq, allowing high sgRNA capture efficiency and identification of possible transcriptional regulatory mechanisms at a single cell/sgRNA level.

  Study EGAS50000001417

• Genomic characterisation of SDH deficient renal cell carcinoma - WGS

  SDH deficient renal cell carcinomas are a rare and recently defined subtype of kidney cancer, often associated with an inherited mutation in one of the SDH gene subunits. This dataset sought to understand the genomic events that underpin tumour formation, from putative cell of origin, characterisation of the tumour microenvironment, to the genomic evolution of these rare tumours. We performed whole genome and RNA sequencing of 4 patients with SDH deficient renal cell carcinomas, including one patient who had an additional paraganglioma. An addition patient in this cohort had the initial diagnosis revised to a clear cell renal cell carcinoma.

  Dataset EGAD00001008469

• 65 prostate cancer cases WGS and transcriptome sequencing project

  We obtained whole-genome and transcriptome sequencing of tumor-benign pairs from 65 Asian prostate cancer (PCa) patients. Taken together with the TCGA PCa cohort, our integration analysis provides the first comprehensive mutational landscape of PCas across major ethnics worldwide and reveals potential novel role of frequent altered chromatin remodeler genes in PCas without androgen receptor (AR) alteration and complex rearrangements derived from Chromoplexy. In addition, we identified 5 putative tumor suppressor genes (TSGs) chains including one on chromosome 13q with novel findings of PCDH9 (deletions in 15/65 tumors) which was implicated in aggressive progression of prostate cancer. Finally, the integrative pathway and co-expression network analysis followed by the functional study indicated the frequent altered genes, particularly focal amplifications of PLXNA1 (11/65), in semaphoring signaling of axon guidance pathway may interact with PI3K/AKT and AR signaling and also contribute to the aggressiveness and progression of prostate cancer.

  Study EGAS00001000888

• HiChIP data and analysis in OCI-AML3

  Data and analysis of HiChIP assay of shZNF143 and shControl in OCI-AML3. CTCF was the ChIP antibody. Data files are paired-end reads in FASTQ format from the Illumina NovaSeq 6000 sequencer. Analysis files are paired-end bed files produced by FitHiChIP.

  Dataset EGAD50000001376

• Human glioblastoma single cell RNA-seq from two patient, sampled at different positions within as well as outside tumor

  We performed deep single-cell RNA sequencing of two rare glioblastoma cases where tissue could be sampled from tumor core to macroscopically normal cortex. We processed two to three replicates per sample with the 10X Genomics V3.1 kits. Deep sequencing was performed to about 100,000 reads per cell on the Illumina NovaSeq 6000 platform, resulting in a total of 37 BAM files.

  Dataset EGAD50000001500

• A comprehensive DNA methylation landscape of human and mouse cell lines derived from hematological malignancies

  The dataset from Infinium Human MethylationEPIC v1.0 (IDAT files) includes 91 primary samples from patients with B-cell acute lymphoblastic leukemia (B-ALL) (n=34) and T-cell acute lymphoblastic leukemia (T-ALL) (n=57). This dataset was used in the article "A Comprehensive DNA Methylation Landscape of Human and Mouse Cell Lines Derived from Hematological Malignancies" to validate differentially methylated CpG sites, which were utilized to classify hematologic malignancies.

  Dataset EGAD50000000888

• Whole genome sequences and variant calls from human cells exposed to UV and CX5461

  Bulk whole genome sequencing data from 38 samples, including patient skin biopsies from 15 patients and RPE-1 cell line data. The targeted sequencing depth was 80X. The dataset also also includes somatic short variants from 15 patients treated with CX5461, and somatic short variants from 3 treatments of 2 genotypes of RPE-1 cells.

  Dataset EGAD50000001640

• RNA-seq data from primary AML samples with t(3;8)

  RNA-seq was generated to investigate differences in gene expression between t(3;8) AML and other primary AMLs. Briefly, sample libraries were prepared using 500 ng of input RNA according to the KAPA RNA HyperPrep Kit with RiboErase (HMR) (Roche) using Unique Dual Index adapters (Integrated DNA Technologies, Inc.). Amplified sample libraries were paired-end sequenced (2x100 bp) on the Novaseq 6000 platform (Illumina

  Dataset EGAD00001006819

• ATAC-seq data from primary AML samples with t(3;8)

  Open chromatin regions in the MYC super-enhancer region were investigated by ATAC-seq in t(3;8) AML. ATAC-seq was performed as described (Buenrostro et al, 2013) with a modification in the lysis buffer (0.30 M sucrose, 10 mM Tris pH 7.5, 60 mM KCl, 15 mM NaCl, 5 mM MgCl2, 0.1 mM EGTA, 0.1% NP40, 0.15 mM Spermine, 0.5 mM Spermidine, 2 mM 6AA) to reduce mitochondrial DNA contamination.

  Dataset EGAD00001007910

• Paired Exome sequencing of 34 samples (tumors and controls) of different tumors

  Paired Exome sequencing of 34 samples (tumors and controls) of different tumors. The samples were prepared using Agilent SureSelect V5+UTRs, the sequencing was done on Illumina HiSeq 4000.

  Dataset EGAD00001009705

• VRK3 depletion in Pontine Diffuse Midline Glioma DMG-K27 altered cells

  In order to investigate possible mechanisms underlying the phenotype of cell fitness decline observed following decrease of VRK3 in pontine DMG-K27 altered cells 7, we examined differences in global gene expression. RNA-seq was performed 44h and 60h post-transduction with two distinct shRNAs targeting VRK3 to be able to evaluate the early impact of VRK3 knock-down (KD) in four independent in vitro models of DMG

  Dataset EGAD00001010097

• Whole Genome Sequencing of JK Family

  In collaboration with Dr David Savage, we have identified a patient with a very unusual phenotype, lacking almost all visceral fat, but showing a massive accumulation of white fat tissue behind her neck and significantly elevated liver fat. Whole exome sequencing of the proband and her unaffected parents and brother has been run previously, however no causative variant has been found and the sequencing coverage was generally poor. We propose to conduct whole genome sequencing of all 4 family members at a depth of 30X.

  Dataset EGAD00001002227

• NOTCH1 orchestrates metabolic reprogramming to drive proliferation in chronic lymphocytic leukemia

  In Chronic lymphocytic leukemia (CLL), NOTCH1 mutations occur in ~10% of cases and are often associated with unmutated IGHV genes, defining a subgroup requiring earlier treatment. Using an engineered CLL cell line, we demonstrated that NOTCH1-mutated cells exhibit increased glucose uptake, oxidative metabolism, and proliferation, driven by enhanced mitochondrial mass and TFAM upregulation. Metabolic assays and stable isotope tracing revealed a greater dependency on glutamine and anabolic pathways in NOTCH1-mutated cells, promoting growth. These findings were validated in a cohort of NOTCH1-mutated patients, highlighting a molecular circuit linking BCR, NOTCH1, and mitochondrial metabolism. This study suggests that metabolic vulnerabilities in NOTCH1-mutated CLL could inform precision medicine strategies.

  Study EGAS50000000981

• Error-corrected targeted sequencing of rectal mucus from patients suspected to have colorectal cancer

  This dataset contains error-corrected next-generation sequencing (ecNGS) data generated from 161 rectal mucus samples. These samples belong to colorectal cancer, adenoma, and control participants. Genomic DNA was extracted and processed using a hybrid-capture panel targeting 50 colorectal cancer–associated genes, incorporating unique molecular identifiers (UMIs) for duplex consensus error correction. Libraries were sequenced on an Illumina NovaSeq 6000 (paired-end 150 bp) producing paired-end FASTQ files. These data support analyses of DNA mutations in CRC detection and progression.

  Dataset EGAD50000002032

• WES data from 165 tumor/germline samples with muscle invasive bladder cancer.

  In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (< pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). WES was performed using DNA from 165 tumors (76x median coverage) and associated germline DNA (46x median coverage). Data provided here consist of 5,828 fastq files for WES.

  Dataset EGAD00001006239

• Ither2 WXS dataset - Implementation of pediatric precision oncology into clinical practice: The individualized Therapies for Children with cancer program “iTHER”

  iTHER is a prospective national precision oncology program aiming to define tumor molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory pediatric tumors in order to identify relevant aberrations to inform treatment.

  Dataset EGAD00001010178

• Ither2 RNA-Seq dataset - Implementation of pediatric precision oncology into clinical practice: The individualized Therapies for Children with cancer program “iTHER”

  iTHER is a prospective national precision oncology program aiming to define tumor molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory pediatric tumors in order to identify relevant aberrations to inform treatment.

  Dataset EGAD00001010179

• High Altitude Pulmonary Hypertension

  The Central Asian Kyrgyz highland population provides a unique opportunity to address genetic diversity and understand the genetic mechanisms underlying hypoxia-induced high altitude pulmonary hypertension (HAPH). While a significant fraction of the population is unaffected, there are susceptible individuals who display HAPH in the absence of any lung, cardiac or hematologic disease. We report herein the analysis of the whole genome sequencing of healthy individuals compared with HAPH patients and other controls. In this study, 34 male individuals from Central Asian Kyrgyz highland are sequenced with Illumina HiSeq 2000 with mean-coverage of 30X.

  Dataset EGAD00001004308

• Broad utility of ultrasensitive analysis of ctDNA dynamics across solid tumors treated with immunotherapy

  Prior studies have suggested the biomarker potential of plasma circulating tumor DNA (ctDNA) in cancer patients treated with immune checkpoint inhibitors (ICIs). In order to characterize the potential role of ultrasensitive ctDNA detection in the management of these patients we have performed tumor whole-genome-informed, ultrasensitive ctDNA analysis—tracking approximately 1,800 tumor-specific mutations per patient—in a retrospective cohort (n=136) and a prospective validation cohort (n=66) across 24 cancer types treated with ICIs alone or in combination with bispecific antibodies or immune cell engagers. Analyzing 1,455 longitudinal samples, we found that ctDNA molecular response measured as early as 3 weeks after treatment initiation correlated with improved progression-free and overall survival, while ctDNA clearance at any time strongly correlated with radiological response and prolonged survival. Additionally, ctDNA dynamics distinguished true progression from pseudoprogression and predicted outcomes in patients receiving continued immunotherapy beyond initial progression. This study highlights the broader applicability of ultrasensitive ctDNA as a biomarker across cancer types and immunotherapy modalities.

  Study EGAS50000001333

• Single-cell analysis of airway samples identifies immune cell activation correlating with COVID-19 disease severity

  To investigate the immune response and mechanisms associated with severe COVID-19, we performed single-cell RNA-seq on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from 5 healthy controls. We identified airway epithelial cell types and states vulnerable to SARS-CoV-2 infection. In COVID-19 patients, epithelial cells showed an average threefold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared with moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand–receptor expression profiles, and activated immune cells , including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF . The transcriptional differences in critical cases compared with moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways may suppress immune hyperactivation in critical COVID-19.

  Study EGAS00001004481

• The long term effects of chemotherapy on normal blood - WGS dataset

  In developed countries, ~10% of individuals are exposed to systemic chemotherapy for cancer and other diseases. Many chemotherapeutic agents act by increasing DNA damage in cancer cells, hence triggering cell death. However, there is limited understanding of the extent and consequences of collateral DNA damage to normal tissues. To investigate the impact of chemotherapy on mutation burdens and cell population structure of a normal tissue we sequenced blood cell genomes from 23 individuals, aged 3-80 years, treated with a range of chemotherapy regimens. Substantial additional mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but there were differences in burden between different classes of agent, different agents of the same class and different blood cell types. Chemotherapy also induced premature changes in the cell population structure of normal blood, similar to those of normal ageing. The results constitute an initial survey of the long-term biological consequences of cytotoxic agents to which a substantial fraction of the population is exposed during the course of their disease management, raising mechanistic questions and highlighting opportunities for mitigation of adverse effects.

  Dataset EGAD00001015339

• Multiomic analysis of CD4+ T cells from blood, lymph node and tumor of NSCLC patients

  This dataset contains data derived from FACS-sorted CD4+ T cells. This dataset contains FASTQ files for: - paired blood, lymph node, and tumor single-cell RNA-seq (scRNA-seq) samples from 5 patients with NSCLC (including scRNA-seq coupled to scTCR-seq for 3 patients), - paired blood, lymph node, and tumor single-cell ATAC-seq (scATAC-seq) samples from 2 patients with NSCLC, - lymph node and tumor bulk RNA-seq and TCR-seq data from CD4+ T cell subsets (Treg-Tfr, Treg-Trm, Treg-Naive, Tconv-Tfh, Tconv-CXCL13, and Tconv-Naive) from 5 patients (one patient has lymph node samples only). In addition, this dataset includes processed analysis files: - Seurat object for scRNA-seq data, - fragment files generated by Cell Ranger for scATAC-seq samples, - contig annotations generated by Cell Ranger for scTCR-seq samples. Sequencing was performed using Illumina NovaSeq, MiSeq, or HiSeq Rapid Run platforms.

  Dataset EGAD50000000424