19385 results for "Cheap fc 26 coins Buyfc26coins.com is official EA Sports partner for FC 26 coins That was the fastest delivery ever..fxB4"

in 46.28 milliseconds.

• Improved T Cell Immunity Following Neoadjuvant Chemotherapy in Ovarian Cancer

  This study characterized the evolution of the peripheral immune cell function and composition across the course of standard of care platinum and taxane chemotherapy in ovarian cancer using bulk and single cell transcriptomic approaches. Serial blood samples were collected from ten patients with advanced high-grade serous ovarian cancer treated with chemotherapy. Single cell sequencing was performed on five patients' samples collected before the initiation of chemotherapy and after the third cycle of chemotherapy.

  Study phs002862

• Single cell transcriptomic data of human gut macrophages

  Cellular suspensions (∼15000 cells, with expected recovery of ∼7500 cells) of sorted CD45+ HLA-DR+ CD14+ macrophages from colonic mucosa and muscularis propria were loaded on the 10X Chromium Controller instrument (10X Genomics) according to the manufacturer’s protocol using the 10X GEMCode proprietary technology. All samples from individual patients were loaded in one batch. The Chromium Single Cell 3´ v2 Reagent kit (10X Genomics) was used to generate the cDNA and prepare the libraries, according to the manufacturer’s protocol. The libraries were then equimolarly pooled and sequenced on an Illumina NextSeq500 using HighOutput flow cells v2.5. A coverage of 400M reads per sample was targeted, in order to obtain 50 000 reads per cell. The raw data were then demultiplexed and processed with the Cell Ranger software (10X Genomics) v2.1.1.

  Dataset EGAD00001007765

• Follow_up_for_second_tier_signals_from_the_arcOGEN_GWAS

  The arcOGEN UK nationwide consortium has been funded by the arc to undertake a genome-wide association scan in osteoarthritis. GWA genotyping has been carried out at the Sanger on the illumina 610k array. This replication study was desinged to follow-up second-tier signals from the arcOGEN GWS in 25 SNPs (1Sequenom iPLEX) with p<5x10^-6 on 6000 additional UK OA and control samples.

  Study EGAS00001001017

• Reference single cell SNP array dataset from Coriell for training and validation of method for accurate single cell genotyping

  This dataset contains DNA from B-lymphocytes from 2 Coriell families and 4 individuals hybridized to HumanKaryomap BeadChip Array. Single cells from subjects GM12878 and GM7228 were amplified using multiple displacement amplification (SureMDA) according to Infium Karyomapping Assay Guide. Bulk DNA was processed and hybridized to an array for subject GM12878, GM07224 and GM07225.

  Dataset EGAD00001006376

• RNA-Seq dataset of Targeting the dark proteome to expand the lineage-retained antigen landscape in neuroblastoma

  This dataset contains bulk RNA-sequencing data generated to enable custom transcriptome assembly and to provide expression context for matched ribosome profiling in the discovery of lineage-retained neuroblastoma tumor antigens. RNA was sequenced from 183 neuroblastoma samples comprising cell lines, patient-derived tumor organoids, and primary patient tumors spanning the adrenergic (ADRN) and mesenchymal (MES) lineage states, with 101 samples prepared as rRNA-depleted (total RNA) libraries and 82 samples prepared as poly(A)-selected libraries. Libraries were sequenced paired-end (2x150 bp) on the Illumina NovaSeq 6000 platform. Raw data are provided as paired-end fastq.gz files.

  Dataset EGAD00001016124

• Alpha synucleinopathy spectrum - bulk RNA seq of prefrontal cortex

  Dataset corresponding to the bulk RNA seq dataset from prefrontal cortex for a total of N=44 samples. Tissue samples correspond to patients with different alpha synucleinopathies. Specifically, idiopathic Parkinson's disease (PD, N=20) monogenic PD caused by LRRK2 mutations (LRRK2-PD, N=7), multiple system atrophy (MSA, N=6) and neurologically healthy controls (N=11). RNA seq was carried out using ribosomal depletion. The totality of these samples were also sequenced using single nucleus RNA seq, and available within the same study as a separate dataset.

  Dataset EGAD50000000430

• Targets of MEK inhibition in DIPG

  The survival of children with diffuse intrinsic pontine glioma (DIPG) remains dismal, with new treatments desperately needed. In the era of precision medicine, targeted therapies represent an exciting treatment opportunity, yet resistance can rapidly emerge, playing an important role in treatment failure. In a prospective biopsy-stratified clinical trial, we combined detailed molecular profiling (methylation BeadArray, exome, RNAseq, phospho-proteomics) linked to drug screening in newly-established patient-derived models of DIPG in vitro and in vivo. We identified a high degree of in vitro sensitivity to the MEK inhibitor trametinib in samples which harboured genetic alterations targeting the MAPK pathway, including the non-canonical BRAF_G469V mutation, and those affecting PIK3R1 and NF1. However, treatment of PDX models and of a patient with trametinib at relapse failed to elicit a significant response. We generated trametinib-resistant clones in the BRAF_G469V model through continuous drug exposure, and identified acquired mutations in MEK1/2 (MEK1_K57N, MEK1_I141S and MEK2_I115N) with sustained pathway up-regulation. These cells showed the hallmarks of mesenchymal transition, and expression signatures overlapping with inherently trametinib-insensitive primary patient-derived cells that predicted an observed sensitivity to dasatinib. Combinations of trametinib with dasatinib and the downstream ERK inhibitor ulixertinib showed highly synergistic effects in vitro. These data highlight the MAPK pathway as a therapeutic target in DIPG, and show the importance of parallel resistance modelling and rational combinatorial treatments likely to be required for meaningful clinical translation.

  Study EGAS00001004495

• NEOPREDICT-Lung: Neoadjuvant Immunotherapy for Resectable NSCLC

  Links via: DOI: https://doi.org/10.1038/s41591-024-02965-0 PubMed: https://pubmed.ncbi.nlm.nih.gov/38689060/ Journal: https://www.nature.com/articles/s41591-024-02965-0 Abstract Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4 administered alone or in combination with chemotherapy are standard of care in most patients with metastatic non-small cell lung cancers. When given prior to curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase II study, 60 biomarker-unselected, treatment-naïve patients with resectable non-small cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was feasibility of surgery within 43 days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (≤10% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab), and 30% and 27% (nivolumab and relatlimab) of patients, respectively. In 100% (nivolumab) and 90% (nivolumab and relatlimab) of patients tumors and lymph nodes were pathologically completely resected. With 12 months median duration of follow-up, disease-free survival and overall survival rates at 12 months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab). Both treatments were safe with grade ≥ 3 treatment-emergent adverse events reported in 10% and 13% of patients per study arm. Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 prior to lung cancer surgery.

  Study EGAS00001007753

• An atlas of transcribed enhancers across helper T cell diversity for decoding human diseases

  At 5' ends of RNAs, there is a unique "cap signature" derived from a 7-methylguanosine cap. By leveraging this signature, we developed ReapTEC (read-level pre-filtering and transcribed enhancer call), a method for simultaneously profiling gene expression and enhancer activities using 5'-end single-cell RNA sequencing (5' scRNA-seq). We applied ReapTEC and single-nucleus ATAC-seq to a total of ~1 million single human CD4+ T cells.

  Study JGAS000689

• Comprehensive analyses of clinicopathological features and genomic mutations of combined hepatocellular-cholangiocarcinoma

  Combined hepatocellular and cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer. We performed whole exome sequencing to clarify the relationship between genetic mutations and clinicopathological features in cHCC-CCA.

  Study JGAS000599

• Genomic Characterization of Metastatic Castration Resistant Prostate Cancer

  Biopsies of castration resistant prostate cancer metastases were subjected to whole genome sequencing (WGS), along with RNA-sequencing (RNA-Seq). The overarching goal of the study is to illuminate molecular mechanisms of acquired resistance to therapeutic agents, and particularly androgen signaling inhibitors, in the treatment of metastatic castration resistant prostate cancer (mCRPC).

  Study phs001648

• Screening_for_abnormal_CGI_methylation_in_primary_colorectal_tumours

  A common hallmark of neoplastic cells is abnormal acquisition of CpG island (CGI) methylation and the silencing of associated gene promoters. To determine the extent and distribution of CGI methylation in colorectal cancer, we solexa sequenced MBD affinity purified DNA prepared from five colorectal tumours and matched colon mucosa from the same individuals.

  Study EGAS00001000076

• Targeted_sequencing_of_candidate_genes_in_calcific_aortic_valve_stenosis

  The objective is to identify new disease genes involved in calcific aortic valve stenosis (CAVS) by screening newly identified candidate genes. The recruitment of patients with CAVS has been achieved by l’institut du thorax (Nantes, France). DNA from the selected patients has been analysed by targeted capture (Agilent SureSelect) and massively parallel sequencing (Illumina).

  Study EGAS00001000308

• Genomic Profiling of Sequentially Acquired Metastatic Sites from an "Exceptional Responder" Lung Adenocarcinoma Patient Reveals Extensive Genomic Heterogeneity and Novel Somatic Variants

  We employed next-generation sequencing to identify somatic alterations in multiple metastatic sites from an "exceptional responder" lung adenocarcinoma patient during his seven year course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ~1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies demonstrated increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy due to L869R mutation and increased migration due to ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a sub-clone metastasized early from the primary site and evolved independently in lymph nodes.

  Study phs001159

• DNA methylation repeatability in the Lothian Birth Cohorts of 1921 and 1936.

  The repeatability of longitudinal measures of whole blood DNA methylation (obtained using the Illumina 450k chip) was assessed in two cohorts of ageing. The Lothian Birth Cohort of 1921 and the Lothian Birth Cohort of 1936. Data were collected at ages 70, 73, and 76 (LBC1936) and 79, 87, 90 (LBC1921) with 478 participants having two or more measures of methylation.

  Study EGAS00001000910

• WES and RNA sequencing of mesothelioma patients from CONFIRM clinical trial

  CONFIRM is a placebo controlled, double-blind randomised phase III clinical trial designed to investigate the efficacy of the anti-PD1 inhibitor nivolumab in patients with relapsed mesothelioma. This study applied the whole exome sequencing and transcriptomic sequencing to uncover determinants of efficacy in patients exhibiting the most extreme response outcomes.

  Study EGAS50000001814

• Host genetic determinants of HIV infection

  Broadly, the objectives of the study are to characterize genetic variation in any gene or genomic region in South African populations, in the first place HIV. The purpose is to apply this knowledge to establish assays and gene signatures to test in disease-association studies, and to study underlying mechanisms of disease causation/severity.

  Study EGAS00001005245

• Melanoma Brain Metastasis Single-Cell RNA Sequencing Atlas

  Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma, yet our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBM (scRNA-seq n=5; snRNA-seq n=17) and 10 extracranial melanoma metastases (ECM; all snRNA-seq), and matched spatial single-cell transcriptomics (n=16) and T cell receptor (TCR)-seq (n=5). Key observations were validated in matched bulk RNA- and ATAC-seq of isogenic MBM/ECM cell culture models (n=24; including triplicates (labeled as *-A, -B and -C) of 4 MBM- and 4 ECM-derived patient cell lines with 2 matched pairs). This work provides comprehensive insights into MBM biology and serves as a foundational resource for further discovery and therapeutic exploration.

  Study phs002944

• Spatial atlas of human atherosclerosis highlights role of the microvasculature in disease

  Atherosclerosis is a pervasive contributor to ischemic heart disease and stroke. Despite the advance of lipid lowering-therapies and antihypertensive agents, the residual risk of an atherosclerotic event remains high and developing therapeutic strategies has proven challenging. This is due to the complexity of atherosclerosis with a spatial interplay of multiple cell types within the vascular wall. Here we generate an integrative high-resolution map of human atherosclerotic plaques combining single-cell RNA-seq from multiple studies and spatial transcriptomics data from 12 human specimens, with different stages of atherosclerosis. We show cell-type and atherosclerosis-specific expression changes and spatially constrained alterations in cell-cell communication. We highlight the possible recruitment of lymphocytes via ACKR1 endothelial cells of the vasa vasorum, the migration of vascular smooth muscle cells towards the lumen by transforming into fibromyocytes, and cell-cell communication in the plaque region, indicating an intricate cellular interplay within the adventitia and the subendothelial space in human atherosclerosis.

  Study EGAS50000000660

• HCA_Thymus_Disease

  Single cell RNA sequencing on thymic cells from children with syndromic diseases such as Trisomy 21 and inflammatory/autoimmune diseases such as myasthenia gravis. Our group has previously performed atlasing of the healthy human thymus using single cell transcriptomics and obtained an unprecedented understanding of human thymus throughout development. In this study, we intend to survey diseased human thymus and compare this to healthy to obtain a better understanding of thymic dysfunction in human diseases. The diseases we will survey include congenital conditions such as Down's syndrome, CHARGE syndrome, DiGeorge syndrome as well as acquired diseases such as myasthenia gravis and thymic hyperplasia. We intend to perform genetic and genomic study on the samples, including expression analysis. This will not only help us to understand the cells and molecular pathways affected in dysfunctional thymus; but may also lead to generalisable understandings in human genetic diseases and inflammatory/autoimmune diseases. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001004310

• Novel optineurin frameshift insertion causing familial frontotemporal dementia and parkinsonism without amyotrophic lateral sclerosis

  Frontotemporal Dementia (FTD) is a common cause of Young Onset Dementia and has diverse clinical manifestations involving behaviour, executive function, language and motor function, including parkinsonism. Up to 50% of FTD patients report a positive family history, supporting a strong genetic basis, particularly in cases with both FTD and amyotrophic lateral sclerosis (FTD-ALS). Mutations in three genes are associated with the majority of familial FTD (fFTD) cases - microtubule associated protein tau gene (MAPT), progranulin gene (PGRN), and hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72), whilst mutations in other genes such as optineurin (OPTN) have rarely been reported. Mutations in OPTN have been reported mostly in familial and sporadic cases of ALS, or in rare cases of FTD-ALS, but not in association with pure or predominant FTD and/or parkinsonian phenotype. Here, we report for the first time, a family from the Philippines with 4 affected members harbouring the same OPTN frameshift insertion, presenting with FTD-related phenotypes, including one sibling with predominant parkinsonism resembling corticobasal syndrome. Notably, none of the affected members showed any evidence of motor neuron disease or ALS at the time of writing, both clinically and on electrophysiological testing, expanding the phenotypic spectrum of OPTN mutations. Close follow-up of mutation carriers for the development of new clinical features and wider investigation of additional family members with further genetic analyses will be conducted to investigate the possibility of other genetic modifiers in this family which could explain phenotypic heterogeneity.

  Study EGAS00001005220

• cfDNA from fractionated and paired unfractionated plasma samples of lung cancer patients

  Plasma from lung cancer patients from EDTA tubes was fractionated using size exclusion chromatography. Fractions 1-5, 7-11, 12-15, 16-20 were pooled, cfDNA was extracted from the fractions and paired unfractionated samples and PE150bp sequencing was performed on an Illumina Novaseq S4 flowcell. Samples are provided as raw reads without any prior processing.

  Dataset EGAD00001009780

• Glioblastoma epigenome profiling identifies SOX10 as a master regulator of molecular tumour subtype

  Glioblastoma in adult patients are classified into four subtypes, IDH, MES, RTK I, and RTK II, based on DNA methylation and RNA expression data. Tumour subtype transitions commonly occur during the treatment of glioblastoma patients, and transitions to the mesenchymal (MES) subtype have been associated with therapy resistance and adverse prognosis. Here, we generate DNA methylome and histone modification data of glioblastoma primary tumours and show that glioblastoma subtypes differ by their enhancer landscapes. Using Core Regulatory Circuitry analysis of H3K27ac data, and independent analysis of RNA-derived gene regulatory networks, we identified 38 subtype master regulators whose cell type-specific activities we mapped in single-cell RNA sequencing data. These analyses identified the chromatin modifier SRY-Box 10 (SOX10) as a master regulator in tumours of the RTK I subtype. In functional studies we demonstrate that SOX10 loss causes a transition of RTK I tumour cells to a mesenchymal cellular state by altering the accessibility of enhancer-rich chromatin regions and their occupancy by Bromodomain Containing 4 (BRD4), a dynamic constituent of super-enhancers. Treatment with the BRD4 inhibitor JQ1 blocked this transition. These data demonstrate the fundamental role of enhancer chromatin remodelling and master regulator activity in the establishment, maintenance and plasticity of glioblastoma cellular states. We also make our data publically browsable at https://dkfz-b060.github.io/gb_browse/

  Study EGAS00001003953

• Singapore Gastric Cancer Consortium GeoMx DSP tissue microarray (SGCC TMA) cohort

  Gastric cancer (GC) remains a significant global health challenge due to its high heterogeneity, with intratumoral heterogeneity (ITH) posing a major obstacle to effective patient outcomes. In this study, utilizing GeoMx Digital Spatial Profiler (DSP) technology, we specifically investigated ITH within GC patients by comparing tumor core regions to tumor edge regions. Our findings indicate that tumor edge regions exhibit more advanced tumor activity, akin to the G2-like progressed state, compared to tumor core regions. The findings confirm the spatial locations of G2 RNA-ITH subregions and support the conclusions drawn from the discovery cohort.

  Study EGAS50000000640

• Heterogeneity and evolution of DNA mutation rates in microsatellite-stable colorectal cancer

  A mutation accumulation experiment in colorectal cancer (CRC) derived tumoroids. A sequential single-cell cloning approach was adopted to measure the mutation rate in eight tumoroids obtained from five patients. WGS was also performed on their matched normal tissue and on standard tumoroids cultures without any cloning step.

  Dataset EGAD50000000411

• Oropharyngeal Squamous Cell Carcinoma Mutanome

  This dataset comprises genetic variation data (as somatic indels and snvs VCFs) of 38 OPSCC tumors. WES was done using NextSeq 500 System running in 150 cycles (2x 75bp paired-end) mode. Sequence information was converted to FASTQ format using bcl2fastq v2.20.0.422. VCFs were generated using the Strelka package.

  Dataset EGAD00001009167

• Germline variants in childhood melanoma

  Whole-exome sequencing was performed on DNA extracted from blood samples of 50 children diagnosed with cutaneous melanoma prior to 18 years of age. Patients were all diagnosed in Queensland, Australia, and self-reported as of European descent. Sequencing was done the Illumina platform using SureSelct V7 Post capture kits.

  Dataset EGAD00001010039

• CCA methylation data (12 CCA, 7 normal)

  Raw idat files for DNA methylation profiling for 12 CCAs and 7 normal bile duct tissues. DNA methylation profiling was performed using Infinium MethylationEPIC v2.0 Kit.

  Dataset EGAD00010002613

• HPS1 patient monocyte-derived macrophage and control macrophage RNAseq with and without infection

  4 HPS1 patient monocyte-derived macrophages and 4 controls were RNA sequenced at baseline and after Salmonella Typhimurium infection. We used paired end sequencing on an Illumina HiSeq 4000. Each sample was run on 3 lanes for sequencing depth, which we combined for our analysis.

  Dataset EGAD00001006978

• Whole exome sequencing data from CD4 T cells, NK cells, monocytes and granulocytes from Alzheimer's disease patients and control individuals

  This dataset contains whole exome sequencing data for 343 samples collected from 118 male donors, including 66 Alzheimer disease patients and 52 controls. DNA for sequencing was extracted from FACS-isolated CD4 T cells, NK cells and myeloid cells (monocytes or granulocytes).

  Dataset EGAD00001015757

• Measurement of the Male Germline Mutation Rate Using Sequential Sperm Samples

  We recalled 23 sperm donors with prior banked samples to provide a new sperm sample. The old and new sequential sperm samples were then profiled by high-fidelity duplex sequencing to measure individual-specific mutation rates and patterns. We also performed deep whole-genome sequencing of sequential sperm samples from two individuals followed by targeted validation, which measured remarkably stable mosaicism of clonal mutations that likely arose during embryonic and germline development.

  Study phs003716

• RNA-seq of cultured human hematopoietic stem and progenitor cells from umblical cord blood in cytokine-rich ex vivo culture conditions following sphingolipid modulation

  In order to elucidate the biological pathways altered by sphingolipid modulation with N-(4-hydroxyphenyl) retinamide (4HPR) treatment in human HSPC that may contribute to the restraint in proliferation while promoting persistence of HSC self-renewal, as well as determine the mechanism of synergy in enhancement of HSC self-renewal with CB CD34+ agonists UM171 and StemRegenin 1 (SR1), we performed RNA-sequencing (RNA-Seq) of 3 pools of lin-CB cells following 2 or 4 days with DMSO, 4HPR, UM171+SR1 or 3-Factor (4HPR+UM171+SR1). We identified modulation of sphingolipid metabolism regulates self-renewal through activating coordinated stress pathways that coalesce on endoplasmic reticulum stress and autophagy programs.

  Dataset EGAD00001005140

• A Randomized Trial of Combined PD-L1 and CTLA-4 Inhibition with Targeted Low-Dose or Hypofractionated Radiation for Patients with Metastatic Colorectal Cancer

  Brief SummaryThis randomized phase II trial studies the side effects of durvalumab and tremelimumab to see how well they work with or without high or low-dose radiation therapy in treating patients with colorectal (CRC) or non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic). Immunotherapy with durvalumab and tremelimumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving durvalumab and tremelimumab with radiation therapy may work better in treating patients with colorectal or non-small cell lung cancer.Detailed DescriptionPRIMARY OBJECTIVES:I. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 (durvalumab) and tremelimumab alone or with high or low-dose radiation in non-small cell lung cancer (NSCLC). (NSCLC Cohort) II. To compare the overall response (excluding the irradiated lesion[s]) between combined checkpoint blockade with MEDI4736 and tremelimumab alone or combined checkpoint blockade with low or high dose radiation. (NSCLC Cohort) III. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 and tremelimumab with high or low-dose radiation. (Colorectal Cohort) IV. To determine the overall response rate (excluding the irradiated lesion[s]) with combined checkpoint blockade with MEDI4736 and tremelimumab with either low or high dose radiation. (Colorectal Cohort)SECONDARY OBJECTIVES:I. To estimate median progression-free survival and overall survival. (NSCLC Cohort) II. To determine local control within the irradiated field(s) and abscopal response rates. (NSCLC Cohort) III. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells and overall response. (NSCLC Cohort) IV. To explore changes in PD-L1 expression, circulating T-cell populations, T-cell infiltration, ribonucleic acid (RNA) expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (NSCLC Cohort) V. To estimate median progression-free survival and overall survival. (Colorectal Cohort) VI. To determine local control within the irradiated field and abscopal response rates. (Colorectal Cohort) VII. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+ CD8+ T-cells and overall response. (Colorectal Cohort) VIII. To evaluate changes between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells induced by targeted low or high dose radiation. (Colorectal Cohort) IX. To explore changes in circulating T-cell populations, T-cell infiltration, RNA expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (Colorectal Cohort)OUTLINE: Patients are assigned to 1 of 2 cohorts. NOTE: This Study is only for Cohort 2. Please see phs003295 for Cohort 1COHORT 1: Patients with NSCLC are randomized to 1 of 3 arms.ARM A: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.ARM C: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses.COHORT 2: Patients with CRC are randomized to 1 of 2 arms.ARM A: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.After completion of study treatment, patients are followed for up to 12 weeks.Official TitleA Phase 2 Study of MEDI4736 (Durvalumab) and Tremelimumab Alone or in Combination With High or Low-Dose Radiation in Metastatic Colorectal and NSCLC Conditions Metastatic Colorectal CarcinomaMetastatic Lung Non-Small Cell CarcinomaStage IV Colorectal Cancer AJCC v7Stage IV Lung Non-Small Cell Cancer AJCC v7Stage IVA Colorectal Cancer AJCC v7Stage IVB Colorectal Cancer AJCC v7 Intervention/Treatment Biological: DurvalumabRadiation: Radiation TherapyBiological: Tremelimumab Other Study ID Numbers NCI-2016-01325NCI-2016-01325 ( Registry Identifier ) (REGISTRY: CTRP (Clinical Trial Reporting Program))17-71910021 ( Other Identifier ) (OTHER: Dana-Farber - Harvard Cancer Center LAO)10021 ( Other Identifier ) (OTHER: CTEP) Molecular Technologies/AssaysIHCmIFOlinkCyTOFRNAseqWES

  Study phs003294

• A practical guide for mutational signature analysis in hematological malignancies

  Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, prognosis, and even treatment decisions. However, the field lacks a consensus on analysis and result interpretation. Using whole-genome sequencing of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia, we compare the performance of public signature analysis tools. We describe caveats and pitfalls of de novo signature extraction and fitting approaches, reporting on common inaccuracies: erroneous signature assignment, identification of localized hyper-mutational processes, overcalling of signatures. We provide reproducible solutions to solve these issues and use orthogonal approaches to validate our results. We show how a comprehensive mutational signature analysis may provide relevant biological insights, reporting evidence of c-AID activity among unmutated CLL cases or the absence of BRCA1/BRCA2-mediated homologous recombination deficiency in a MM cohort. Finally, we propose a general analysis framework to ensure production of accurate and reproducible mutational signature data.

  Dataset EGAD00001005028

• Epigenomic profile of diverse cancer

  The samples are from patients of multiple cancer types. The library preparation protocol was developed by the laboratory. The DNA libraries were then sequenced with 150bp paired-end reads.

  Dataset EGAD00001006124

• Immune Cell Atlas of Environmental and Ancestral Diversity in Indonesia [WGS]

  This dataset contains low‑pass whole‑genome sequencing data from 203 individuals representing four Indonesian populations: the general urban population of Denpasar and the traditional community of Pedawa Village in Bali, as well as traditional community of Yoboi Village (in Sentani lake) and Sereh Village (individuals from highland Papua residing near Sentani lake) in Papua. Sequencing was performed by Gencove using their low‑coverage whole‑genome platform. The dataset was produced as part of the Immune Cell Atlas of Environmental and Ancestral Diversity in Indonesia, a study aimed at characterizing how genetic background and environmental context shape immune cell states across diverse Indonesian communities.

  Dataset EGAD50000002384

• Comparison between b2m KO and US2 expressing iPSC lines

  This dataset contains bulk RNA-seq transcriptomic profiles from a human induced pluripotent stem cell (hiPSC) line and three engineered derivatives: B2M knockout, EGFP overexpression, and US2 overexpression, alongside the parental line. Total RNA integrity was assessed using the Experion RNA StdSens 1K Analysis Kit on the Bio-Rad Experion Automated Electrophoresis System prior to library preparation and sequencing. Libraries were sequenced on an Illumina NovaSeq 6000 generating ~20 million reads per sample. Raw read quality was assessed with FastQC, reads were aligned to the human reference genome hg38 (Ensembl release 109) using STAR, and alignment/library QC metrics (e.g., orientation, composition, coverage) were evaluated with Picard.

  Dataset EGAD50000002321

• Exome Sequencing of Spanish Patients with rare genetic diseases.

  Whole exome sequencing of Spanish patients suffering from a rare genetic disease. The study was carried out in 2013 as a part of a public call from CNAG (Centro Nacional de Análisis Genómico), where data of eight spanish families were sent to analyse. The study concluded with three solved cases: two of aniridia and one syndromic RP.

  Study EGAS00001004028

• Single-cell RNA-seq of human kidney tumors

  Fresh nephrectomy samples were collected from a total of 5 untreated ccRCC patients. Out of these 5 patients, 7 samples were obtained. Two samples consisted of fresh versus frozen single cells from the primary tumor site of one patient. Two other samples consisted of matched primary and distant thrombus sites (the vena cava) of a second patient. The three remaining samples came from the primary tumor sites of three distinct ccRCC patients. Single-cells were captured into 10x barcoded gel beads and RNA-sequencing library preparation was done using Chromium Single Cell 3' v2 chemistry. Sequencing was performed on a Illumina HiSeq 4000 sequencer.

  Dataset EGAD00001009306

• SNP genotyping of the HLA and T cell receptor regions

  This dataset contains genotype information (vcf files) for genotyped SNPs within or near (within 1 million bases) the HLA and TCR (TRA and TRB) loci of 187 individuals (98 controls and 89 subjects with coeliac disease). SNPs were genotyped using an Axiom Human Genotyping SARS-CoV-2 Research Array (Thermo Fisher) and the data was processed with the Axiom Analysis Suite using the “Best Practices Workflow” pipeline. The genotyped SNPs include 6791 SNPs within/near the HLA region on Chr6, 685 SNPs within/near TRA on Chr14, and 262 SNPs within/near TRB on Chr7 passing quality control. The dataset also contains a metadata file (csv) describing sample phenotypes and providing links to genotype sample names.

  Dataset EGAD50000002728

• Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens

  Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by laser microdissection from thin sections across spatially separated levels of ten high-grade serous ovarian carcinomas (HGSOCs) and analyzed by mass spectrometry, reverse phase protein arrays, and RNA sequencing. Unsupervised analyses of protein abundance data revealed independent clustering of an enriched stroma and enriched tumor epithelium, with whole tumor tissue clustering driven by overall tumor “purity.” Comparing these data to previously defined prognostic HGSOC molecular subtypes revealed protein and transcript expression from tumor epithelium correlated with the differentiated subtype, whereas stromal proteins (and transcripts) correlated with the mesenchymal subtype. Protein and transcript abundance in the tumor epithelium and stroma exhibited decreased correlation in samples collected just hundreds of microns apart. These data reveal substantial tumor microenvironment protein heterogeneity that directly bears on prognostic signatures, biomarker discovery, and cancer pathophysiology and underscore the need to enrich cellular subpopulations for expression profiling.

  Dataset EGAD00001008344

• Chinese Alternating Hemiplegia of Childhood (AHC) Disease Study

  AHC is a rare and severe neurological disorder, and characterized by episodic hemiplegia or quadriplegia attacks, accompanied by other paroxysmal symptoms of oculomotor abnormalities, dystonia, seizures and autonomic disturbances; the age of onset usually occurrs before 18 months of life. Sodium-potassium ATPase alpha3 subunit (ATP1A3) has recently been identified as a causal gene for sporadic AHC by three groups. However, there has not been any large genetic study on a Chinese cohort. In the submitted data, whole-exome sequencing of three trios and three sporadic cases in a Chinese cohort produced an average of 18.8 gigabases of raw sequence. Through our analysis pipeline including BWA mapping, GATK recalibration, variant calling and filtering, all six patients contained missense mutations in ATP1A3 which were further confirmed as de novo mutations. Along with validation in additional patients, this study confirmed ATP1A3 as a causal gene in Chinese AHC patients, and reported six novel mutations.

  Study phs000660

• Exome sequencing of Congenital Heart Disease families Leuven

  This project aims to study at least 90 exomes from families with congenital heart disease. The samples have been selected in Leuven in collaboration with Koen Devriendt. Ethic approval has been sought for in Leuven, Belgium and a HDMMC agreement for submitting these samples is in place at the WTSI. The phenotype we wil primarily focus our analysis is severe Left Ventricular Outflow Tract Obstructions (LVOTO) and Atrioventricular Septal Defect (AVSD). The indexed Agilent whole exome pulldown libraries will be sequenced on 75bp PE HiSeq (Illumina).

  Dataset EGAD00001000796

• Whole-Genome Sequencing (WGS) of a Malignant Granular Cell Tumor (GCT) with Metabolic Response to Pazopanib

  We report one case study of a malignant granular cell tumor patient with metabolic response to pazopanib. In this study, we used whole-genome sequencing of the tumor with the matched blood to characterize the somatic mutation profile in this tumor. This is the first reported whole-genome sequencing study of the rare malignant granular cell tumor.

  Study phs000978

• The_International_1q_type_2_diabetes_consortium

  The aim of this project is to identify rare variants in the 1q region associated with type 2 diabetes. To this end 651 case samples and 651 control samples from six populations have been pooled (pool sizes range from 27-33 individuals), and are being sequenced. The hybridization solution being used captures the exons and UTRs of genes in the 1q region.

  Study EGAS00001000062

• Development, maturation and maintenance of human prostate inferred from somatic mutations

  Stem cells within prostate epithelium frequently undergo malignant transformation, but there is limited information on their clonal dynamics and mutation burden in healthy human prostates. We sequenced whole genomes from 409 microdissections of prostate epithelium across 8 donors, using phylogenetic reconstruction with spatial mapping in a 59-year-old man’s prostate to provide high-resolution reconstruction of tissue dynamics across the lifespan. Somatic mutation burden increases linearly with age, at ~16 mutations/year/clone, and is higher in peripheral than peri-urethral regions. The 24-30 independent glandular subunits are established as rudimentary ductal structures during fetal development by 5-10 embryonic cells each. Puberty induces formation of further side branches and terminal acini by local stem cells disseminated through the rudimentary ducts during development. During adult tissue maintenance, clonal expansions are small, with limited geographic scope and minimal migration. Driver mutations are rare in normal ageing prostate epithelium, but the one canonical driver we did observe generated a sizable intraepithelial clonal expansion. By resolving unbiased, continuously occurring lineage-marking mutations, we define stem cell dynamics through embryogenesis, puberty and ageing, with relevance for prostate cancer.

  Dataset EGAD00001006591

• Dnase1l3 deletion causes aberrations in length and end-motif frequencies in plasma DNA

  We showed that mice in which Dnase1l3 had been deleted showed aberrations in the fragmentation of plasma DNA. We also observed a change in the ranked frequencies of end motifs of plasma DNA caused by the Dnase1l3 deletion.

  Dataset EGAD00001005071

• Genomic profiling identified ERCC2 helicase domain mutations respond to platinum-based neoadjuvant therapy in urothelial bladder cancer

  Genomic profiling of tumours enables therapeutic decisions, and identifying drug-matched mutations will prolong survival and prognosis. Here, we generated a custom panel for detecting genetic alterations in 19 patients with urothelial bladder cancer. This panel targeted 71 genes associated with urological cancer. Targeted sequencing was performed on formalin-fixed paraffin-embedded tumour tissues. In this study, we revealed genome profiles and actionable mutations in patients with urothelial bladder cancer.

  Study JGAS000241

• Whole blood transcriptomic analysis of ANCA-associated vasculitis

  Whole blood mRNA sequencing from 30 patients with AAV (granulomatosis with polyangiitis/GPA, n=22) and microscopic polyangiitis (MPA, n=8) combined with functional enrichment and network analysis for aberrant pathways. Key genes and pathways were validated in an independent cohort of 18 AAV patients. Co-expression network and hierarchical clustering analysis, identified molecular endotypes. Multi-level transcriptional overlap analysis to SLE was based on our published data from 142 patients.

  Study EGAS00001006704

• Whole genome sequencing of matched patient sample sets of normal and tumor DNA

  Sixteen matched, male and female patient sample sets, each comprising normal DNA, tumor DNA, and RNA, were processed for storage comparison studies. Upon receipt, 10 μl quality control aliquots were prepared from each sample. DNA samples were characterized using Qubit dsDNA High Sensitivity assay for quantification, Genomic DNA TapeStation for integrity assessment (DIN scores), and NanoDrop for purity evaluation. RNA samples were analyzed using Qubit RNA High Sensitivity assay, RNA TapeStation (RIN scores), and NanoDrop. Each sample was divided equally by volume for parallel processing.

  Dataset EGAD50000002441

• Cancer-Restricted Cryptic Antigens Are Targets for T Cell Recognition

  Subjects included patients with pancreatic cancer, at least 18 years of age, who were recruited from outpatient clinics and inpatient units at Dana-Farber Cancer Institute and Brigham and Women's Hospital.Bulk and single-cell transcriptomic profiling of human pancreatic cancer patient samples (direct from tumor or profiling of patient-derived organoids) was performed. Patient-derived pancreatic cancer organoids were profiled in the presence or absence of interferon-gamma stimulation. Healthy-donor CD8 T lymphocytes were ex vivo primed and expanded with candidate non-canonical (cryptic) peptide antigens. Single-cell transcriptomic profiling with paired T cell receptor (TCR) sequencing and molecularly-barcoded HLA tetramers enabled deconvolution and identification of cryptic antigen-reactive TCRs.

  Study phs003887

• Genomic Profile of Multiple Localised Spiradenoma and Spiradenocarcinoma

  Multiple spiradenomas and spiradenocarcinoma from a single donor were subjected to exome sequencing. Tumor samples were microdissected from formalin-fixed, paraffin-embedded tissue, and genomic DNA was extracted. The DNA samples were subjected to library generation using the xGen ssDNA & Low-Input DNA Library Preparation Kit, followed by exome capture using the xGen Exome Research Panel v2. The libraries were sequenced on DNBSEQ G400RS. Reads were aligned to GRCh37 with BWA.

  Study EGAS50000000554

• Spatial Heterogeneity in CLL

  A whole-genome/exome sequencing (WGS/WES) characterization of the spatial heterogeneity found in chronic lymphocytic leukemia (CLL) at diagnosis. Fifteen synchronous peripheral blood and lymph node samples were analyzed by WGS (n=2) or WES (n=13). Subtle differences in the global architecture of the tumor at peripheral blood and lymph node were observed only in a fraction of patients. Spatial heterogeneity was not found among the well-established CLL driver alterations.

  Study EGAS00001003803

• sWGS of Pap test smears from healthy donors and HGSOC patients and matched tumor tissue

  Shallow whole genome sequencing was performed on Pap test smears considering at least 10 M reads per sample. The cohort consists of 77 samples from healthy women, i.e. no tumor diagnosis, and 65 samples from women with a diagnosis of high-grade serous ovarian cancer (HGSOC) taken months or years before diagnosis. 44 primary tumor samples matched to the respective HGSOC patients were sequenced in the same manner as the Pap test smears.

  Study EGAS00001007084

• Discovery of Non-ETS Gene Fusions in Human Prostate Cancer using Next Generation RNA Sequencing

  Half of prostate cancers harbor gene fusions between TMPRSS2 and members of the ETS transcription factor family. To date little is known about the presence of non-ETS fusion events in prostate cancer. We employed next-generation transcriptome sequencing (RNA-Seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes ETV1 and ERG, and five involving non-ETS genes such as CDKN1A (p21), CD9 and IKBKB (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene RSRC2. The novel gene fusions are found to be of low frequency but interestingly, the non-ETS fusions were all present in prostate cancer harboring the TMPRSS2-ERG gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement prone phenotype.

  Study phs000310

• ECL_onc_biology_DAC

  This DAC can be used by biology members of the oncology-related domain and function of ECL when depositing data. (DAA was reviewed by the legal department in March 2024.)

  Dac EGAC50000000275

• AfricanNeo aDNA Study

  With the largest genomic dataset to date of Bantu-speaking populations, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we shed fresh light on the expansion of peoples speaking Bantu languages that started ~4000 years ago in western Africa. We have generated whole-genome sequences from 12 Late Iron Age individuals. Our comprehensive genetic analysis of the expansion of people speaking Bantu languages reveals a complex history of serial founder events, variable levels of contact with local groups, and spread-over-spread events.

  Study EGAS00001007519

• BAM files from whole-exome sequencing of 5 agressive B-cell lymphoma tumour samples

  This dataset contains BAM files from whole-exome sequencing (WES) of 5 agressive B-cell lymphoma tumour samples for cases 2, 3, 4 and 5. For case 2, non-tumor whole-exome sequencing is also available.

  Dataset EGAD50000000803

• Phase IB/II Study of Bazedoxifene in Combination with Palbociclib in Patients with Endocrine Resistant Hormone Receptor-Positive Breast Cancer

  In this phase Ib/II clinical trial, the investigators evaluated the efficacy and safety of the combination of palbociclib with bazedoxifene in patients with a metastatic endocrine-resistant hormone receptor-positive, HER2-negative breast cancer. Furthermore, whole exome sequencing of cell-free tumor DNA was done on serial samples from these patients, revealing potential molecular changes associated with mechanisms of resistance.

  Study phs002802

• VariantMedium: Sensitive and generalizable somatic point mutation calling with 3D DenseNets trained and evaluated on experimental confirmation data

  This study contains whole-exome sequencing (WES) and results of targeted deep-sequencing data of three matched tumor and normal cell lines, with two technical WES replicates each. The calls by Mutect2, Strelka2, and VariantMedium were confirmed using targeted deep sequencing on Illumina Miseq The targeted deep sequencing was performed in three runs and the results are summarized under VCF files.

  Study EGAS50000001661

• WES of sorted B lineage cells from patients with plasma cell neoplasms

  Whole-exome sequencing (WES) was conducted on cell populations isolated from each patient—diagnosed with either multiple myeloma (MM) or light-chain amyloidosis (AL) —including CD34⁺ hematopoietic progenitors, B-cell precursors, mature B cells, normal plasma cells, and clonal plasma cells. In the control cohort of healthy adults, the same target cell populations were analyzed, with the exception of clonal plasma cells, which were absent.

  Study EGAS50000001498

• H3K27ac ChIP-seq in primary inflammatory (TPP) macrophages

  We investigated an intergenic haplotype on chr21q22, linked to five different inflammatory diseases, and identified the molecular mechanism by which the risk haplotype increases expression of the causal gene, ETS2. This mechanism was predicted to alter enhancer activity at the disease-associated locus. We therefore performed H3K27ac ChIP-seq in inflammatory macrophages from minor and major allele homozygotes at the causal allele and investigated the effect on enhancer activity. In doing so, we mechanistically delineated how the risk haplotype increases expression of ETS2.

  Study EGAS00001007562

• Chromatin accessibility analysis of epidermal keratinocytes from psoriatic, clinically healed, and healthy control skin

  This study uses ATAC-seq to analyze epidermal keratinocytes from psoriatic lesions, clinically healed skin of the same patients, and healthy control skin. The aim is to elucidate chromatin accessibility changes associated with psoriasis pathogenesis and remission from 6 lesional, 6 healed, and 5 control samples.

  Study JGAS000844

• Predictor_ChemoNEAR_TNBC

  In this study a collection of core biopsies from breast cancer patients receiving neoadjuvant chemotherapy as part of the ChemoNEAR trial will be investigated. The study is intended to detect early acquired resistance in women with diagnosed breast carcinoma. Samples will undergo whole genome sequencing and analysis, including use of HR Predict.

  Study EGAS00001002806

• MDS Sequencing Project_Cancer Cell

  Myelodysplastic syndromes (MDS) are uncommon entities, heterogeneous clinically and cytogenetically. The aim of the present study is to determine genetic alteration in this subset of patients. Expected results: Identification of new aberrations and genetic markers in order to detect novel genes involved in MDS 5q-response to Lenalidomide's treatment.

  Study EGAS00001001011

• Platelet_collagen_defect

  As part of the Bloodomics collaboration we have several categories of pedigrees with diseases/syndromes relevant to cardiovascular diseases (CVD). One such pedigree, is from families who have a platelet collagen defect. Exome sequencing has been performed as part of a discovery program to ascertain potential causative variants of the clinical phenotype.

  Study EGAS00001000105

• ENU_HT_29_BRAF_Triple_Therapy_Clones

  KRAS mutant CRC is currently in clinical trial with a combination of a MEK and Akt inhibitor. These patients will likely develop resistance to this combination. We aim to identify the mechanisms of resistance via ENU mutagenesis, with a view to identifying additional therapeutics which have the ability to overcome this resistance.

  Study EGAS00001001778

• Melanoma_brain_metastases

  This is a whole exome study of brain metastases in melanoma. We are studying the genomic evolution of primary cutaneous melanoma to brain met in patients with brain-only metastatic disease. We are also looking at the genomic heterogeneity in patients with temporally, anatomically and regionally separated brian metastases.

  Study EGAS00001002107

• Identification of immune mechanisms associated with the high rate of relapse in patient with visceral leishmaniasis and HIV co-infection

  RNA-seq transcriptomics of whole blood samples from longitudinal follow-up of a cohort of visceral leishmaniasis (VL) patients with and without HIV coinfection, from active disease through apparent cure and potential relapse. Analysis will identify potential correlates of relapse to identify immune mechanisms underlying the high rate of relapse in HIV/VL coinfection. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ .

  Dataset EGAD00001008361

• Dataset-linking-WGS-samples-in-ega-box-81-via-README-for-study-EGAS00001002923

  This dataset contains 318 Tumor and Control WGS files submitted in another EGA box for samples for Gerhauser et al.,Cancer Cell, 2018, 34:996-1011. WGS and sequencing protocol was earlier described in Weischenfeldt et al, Cancer Cell, 2013.

  Dataset EGAD00001007861

• Genome Instability in Mammary Cells of Pathogenic BRCA1/2 Mutation Carriers

  It remains unknown if inherited germline mutations in the BRCA1 or BRCA2 gene increase the risk of breast and ovarian cancer by elevating mutation rate in mammary cells. Here we show, using a single-cell whole genome sequencing approach, that mammary luminal epithelial cells isolated from tissues obtained from preventive mastectomy surgeries in women with a pathogenic BRCA1/2 germline mutation, exhibit a statistically significant, increased mutation frequency as compared to age-matched controls without genetic risk of breast cancer.

  Study phs002411

• Oncogenomics of Malignant Peripheral Nerve Sheath Tumors

  Malignant peripheral nerve sheath tumors (MPNSTs) are a group of highly aggressive soft tissue sarcomas that may occur sporadically, in association with neurofibromatosis type I (NF1-associated), or after radiotherapy (RT-associated). We utilized comprehensive genomic approaches and identified recurrent loss-of-function somatic alterations in the Polycomb repressive complex 2 (PRC2) core components EED or SUZ12. Genetic loss of either of these two genes results in complete loss of H3K27me3 and aberrant transcriptional programming in the affected tumors.

  Study phs000792

• Mutations conferring differential treatment response in breast cancer

  Poor prognosis primary breast cancer patients usually receive cytotoxic chemotherapy as a component of treatment, but despite this aggressive therapy recurrences remain common. Improved understanding of chemoresistance pathways would allow better stratification of chemotherapy using predictive markers, and may allow therapeutic inhibition of resistance mechanisms in order to chemosensitise tumours. We aimed to identify molecular pathways that define chemoresponse using the novel approach of examining the selection exerted by neoadjuvant chemotherapy on sub-clonal somatic mutational profiles of cancer cells.

  Study EGAS00001003626

• RNAseq - Discovery of resistance mechanisms to the BRAF inhibitor vemurafenib in metastatic BRAF mutant melanoma

  We propose to biopsy 20 consented BRAF mutant melanoma patients at Addenbrooke's Hospital pre-treatment with vemurafenib and also upon the development of resistant disease, with the aim of using exome sequence and SNP6 data to identify novel sequence variants and copy number alterations that can be used to validate observed resistance mechanisms in our cell line models and also to use these models to inform as to likely candidate small molecule inhibitors to overcome resistance and that could be tested in the clinical trial setting.

  Dataset EGAD00001001050

• Discovery of resistance mechanisms to the BRAF inhibitor vemurafenib in metastatic BRAF mutant melanoma

  We propose to biopsy 20 consented BRAF mutant melanoma patients at Addenbrooke's Hospital pre-treatment with vemurafenib and also upon the development of resistant disease, with the aim of using exome sequence and SNP6 data to identify novel sequence variants and copy number alterations that can be used to validate observed resistance mechanisms in our cell line models and also to use these models to inform as to likely candidate small molecule inhibitors to overcome resistance and that could be tested in the clinical trial setting.

  Dataset EGAD00001001046

• Unravelling the contribution of HIF pathway and its therapeutic potential in human AML leukemia-initiating cells

  This study hypothesized that hypoxia contributes to AML-LSCs function and represents a potential therapeutic target to sensitize AML-LSCs to chemotherapy. We provide a comprehensive single-cell expression atlas of AML patient-matched diagnostic-relapsed samples from risk-stratified human AML patients.

  Study EGAS00001005980

• Elucidating the development of cervical cancer and identifying therapeutic targets based on cancer genome analysis.

  The objective of this project is to analyze genomic aberrations and gene expression changes, such as mutations, deletions, and amplifications, in human cervical cancer cells at the somatic cell level, and to contrast these with clinicopathological information to elucidate the molecular mechanisms and characteristics of lcervical cancer development and progression at the genetic level.

  Study JGAS000803

• Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses

  We show that DNA methyltransferase inhibitors (DNMTis) upregulate immune signaling in cancer through the viral defense pathway and re-expression of epigenetically silenced endogenous retrovirus. In melanoma patients treated with an immune checkpoint therapy, high viral defense signature expression in tumors significantly associates with durable clinical response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical melanoma model.

  Study phs001038

• Single cell atlas of relapsed/refractory large B-cell lymphoma

  Relapsed/refractory large B-cell lymphomas (rrLBCL) are clinically and biologically diverse lymphoid malignancies with intricate microenvironments that play a key role in disease development. In this study, we used single-nucleus multiome profiling along with bulk DNA and RNA sequencing on 120 tumor and control biopsies to comprehensively characterize the various cell types and subsets found in rrLBCL tumors.

  Study EGAS50000001293

• Indonesian Microbiome Ecology and Evolution

  This study investigates patterns of human gut microbiome variation across Indonesia. We performed metagenome-assembled genome (MAG) assembly and employed genome-resolved methods to quantify and characterise microbial abundance within and across sampled communities, that span hunter-gatherer, agricultural and urban contexts. Paired with lifestyle, diet and biometric metadata, this study seeks to disentangle the drivers of microbiome variation across communities, lifestyle and geography.

  Study EGAS50000000961

• Sample Multiplexing Oligo Comparison

  In this study, we compared various multiplexing reagents, including MULTI-Seq, Hashtag antibody, and CellPlex, in patient-derived xenografts (PDXs). We found that all multiplexing reagents worked well in cell types robust to ex vivo manipulation but suffered from signal-to-noise issues in more delicate sample types. We also compared the performance of fixed scRNA-Seq kits and CRISPR-based destruction of non-informative genes.

  Study EGAS50000000153

• Cell-Free DNA Fragmentation Distinguish Immunotherapy Responders from Non- Responders in Head and Neck Cancer: A Multi-Institute Prospective Study

  We performed whole-genome sequencing of 185 plasma cfDNA samples from 68 patients with head and neck squamous cell carcinoma (HNSCC) enrolled in a phase II clinical trial of neoadjuvant and adjuvant pembrolizumab. Using these data, we developed the regional motif diversity score (rMDS), a novel fragmentomic biomarker that predicts immunotherapy response and outperforms established cfDNA metrics.

  Study EGAS50000001286

• Raw sequencing of single-cell RNA-seq data of a phase II clinical trial (NCT03419481)

  This is a single-arm Phase II trial of pembrolizumab in patients with hepatitis B virus-related hepatocellular carcinoma with parallel study on baseline and serial change in the immune environment.

  Study EGAS50000001315

• Targeted sequencing data of cfDNA, archival tissue, and WBC from 208 patients with mUC

  Targeted tissue (n=81), cfDNA (n=319), and WBC (n=208) Illumina sequencing of metastatic urothelial carcinoma patients. All cfDNA is collected in the metastatic setting, while archival tissue is from across the disease course. White blood cell (WBC) samples are used as patient matched germline samples. All files are in paired-end fastq format.

  Dataset EGAD50000002089

• Targeted sequencing data of cfDNA, archival tissue, and WBC from 226 patients with mUC

  Targeted tissue (n=210), cfDNA (n=402), and WBC (n=245) Illumina sequencing of metastatic urothelial carcinoma patients. All cfDNA is collected in the metastatic setting, while archival tissue is from across the disease course. White blood cell (WBC) samples are used as patient matched germline samples. All files are in paired-end fastq format.

  Dataset EGAD50000001571

• Genomic and Transcriptomic Profile of Paired Primary-Metastasis Colorectal Tumors

  The goal of this study is to identify mechanisms of metastization in a portuguese cohort of colorectal cancer. Namely, we want to identify patterns of genomic and transcriptomic diversification associated with metastasis.

  Study EGAS00001005276

• Durvalumab Plus Tremelimumab Alone or in Combination with Low-Dose or Hypofractionated Radiotherapy in Metastatic Non-Small-Cell Lung Cancer Refractory to Previous PD(L)-1 Therapy: an Open-Label, Multicentre, Randomised, Phase 2 Trial

  Brief SummaryThis randomized phase II trial studies the side effects of durvalumab and tremelimumab and to see how well they work with or without high or low-dose radiation therapy in treating patients with colorectal or non-small cell lung cancer that has spread to other parts of the body (metastatic). Immunotherapy with durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving durvalumab and tremelimumab with radiation therapy may work better in treating patients with colorectal or non-small cell lung cancer.Detailed DescriptionPRIMARY OBJECTIVES:I. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 (durvalumab) and tremelimumab alone or with high or low-dose radiation in non-small cell lung cancer (NSCLC). (NSCLC Cohort) II. To compare the overall response (excluding the irradiated lesion[s]) between combined checkpoint blockade with MEDI4736 and tremelimumab alone or combined checkpoint blockade with low or high dose radiation. (NSCLC Cohort) III. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 and tremelimumab with high or low-dose radiation. (Colorectal Cohort) IV. To determine the overall response rate (excluding the irradiated lesion[s]) with combined checkpoint blockade with MEDI4736 and tremelimumab with either low or high dose radiation. (Colorectal Cohort)SECONDARY OBJECTIVES:I. To estimate median progression-free survival and overall survival. (NSCLC Cohort) II. To determine local control within the irradiated field(s) and abscopal response rates. (NSCLC Cohort) III. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells and overall response. (NSCLC Cohort) IV. To explore changes in PD-L1 expression, circulating T-cell populations, T-cell infiltration, ribonucleic acid (RNA) expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (NSCLC Cohort) V. To estimate median progression-free survival and overall survival. (Colorectal Cohort) VI. To determine local control within the irradiated field and abscopal response rates. (Colorectal Cohort) VII. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+ CD8+ T-cells and overall response. (Colorectal Cohort) VIII. To evaluate changes between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells induced by targeted low or high dose radiation. (Colorectal Cohort) IX. To explore changes in circulating T-cell populations, T-cell infiltration, RNA expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (Colorectal Cohort)OUTLINE: Patients are assigned to 1 of 2 cohorts. NOTE: This Study is only for Cohort 1. Please see phs003294 for Cohort 2COHORT 1: Patients with NSCLC are randomized to 1 of 3 arms.ARM A: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.ARM C: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses.COHORT 2: Patients with CRC are randomized to 1 of 2 arms.ARM A: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.After completion of study treatment, patients are followed for up to 12 weeks.Official TitleA Phase 2 Study of MEDI4736 (Durvalumab) and Tremelimumab Alone or in Combination With High or Low-Dose Radiation in Metastatic Colorectal and NSCLC Conditions Metastatic Colorectal CarcinomaMetastatic Lung Non-Small Cell CarcinomaStage IV Colorectal Cancer AJCC v7Stage IV Lung Non-Small Cell Cancer AJCC v7Stage IVA Colorectal Cancer AJCC v7Stage IVB Colorectal Cancer AJCC v7 Intervention/Treatment Biological: DurvalumabRadiation: Radiation TherapyBiological: Tremelimumab Other Study ID Numbers NCI-2016-01325NCI-2016-01325 ( Registry Identifier ) (REGISTRY: CTRP (Clinical Trial Reporting Program))17-71910021 ( Other Identifier ) (OTHER: Dana-Farber - Harvard Cancer Center LAO)10021 ( Other Identifier ) (OTHER: CTEP) Molecular Technologies / AssaysCyTOFIHCmIFOlinkRNAseqWES

  Study phs003295

• Polyclonal selection of immune checkpoint mutations in thyroid autoimmunity - TargetedEMSeq

  Our immune system contains multiple tolerance checkpoints to prevent the activation of self-reactive lymphocytes. How some lymphocytes escape these constraints to cause autoimmune disease remains poorly understood. A long-standing hypothesis in autoimmunity posits that somatic mutations in immune regulatory genes may enable self-reactive lymphocytes to bypass tolerance checkpoints. However, testing this hypothesis has proved challenging due to technical limitations in detecting somatic mutations in polyclonal cell populations. Here, we use deep whole-exome and targeted NanoSeq, a highly accurate single-molecule DNA sequencing protocol, to comprehensively search for driver mutations in autoimmune thyroid disease. This revealed a remarkably high number of B cell clones convergently acquiring loss-of-function somatic mutations in key immune checkpoint genes TNFRSF14 (also known as HVEM) and CD274 (encoding PD-L1), as well as less frequent driver mutations in a diversity of other immune genes. In highly inflamed biopsies, we detected tens to hundreds of independent immune-checkpoint mutant clones. Laser capture microdissection, methylation sequencing, spatial transcriptomics, immunohistochemistry and single-nucleus DNA sequencing localised these mutations to non-naive B cells and revealed frequent co-occurrence of drivers in single cells. We found widespread TNFRSF14 biallelic loss in mutant B cells, and several clones with as many as 4-6 driver mutations. Whilst each clone accounts for a small proportion of cells (typically <1%), the myriad mutant clones in each donor collectively amounted to a substantial fraction of B cells harbouring one or more driver mutations. Our results support the hypothesis that somatic mutations in autoimmune lymphocytes may allow them to escape tolerance constraints through a polyclonal cascade of somatic evolution. These findings provide new insights into the molecular basis of autoimmune disease and suggest novel diagnostic and therapeutic avenues.

  Dataset EGAD00001016060

• Polyclonal selection of immune checkpoint mutations in thyroid autoimmunity - PTA_WGS

  Our immune system contains multiple tolerance checkpoints to prevent the activation of self-reactive lymphocytes. How some lymphocytes escape these constraints to cause autoimmune disease remains poorly understood. A long-standing hypothesis in autoimmunity posits that somatic mutations in immune regulatory genes may enable self-reactive lymphocytes to bypass tolerance checkpoints. However, testing this hypothesis has proved challenging due to technical limitations in detecting somatic mutations in polyclonal cell populations. Here, we use deep whole-exome and targeted NanoSeq, a highly accurate single-molecule DNA sequencing protocol, to comprehensively search for driver mutations in autoimmune thyroid disease. This revealed a remarkably high number of B cell clones convergently acquiring loss-of-function somatic mutations in key immune checkpoint genes TNFRSF14 (also known as HVEM) and CD274 (encoding PD-L1), as well as less frequent driver mutations in a diversity of other immune genes. In highly inflamed biopsies, we detected tens to hundreds of independent immune-checkpoint mutant clones. Laser capture microdissection, methylation sequencing, spatial transcriptomics, immunohistochemistry and single-nucleus DNA sequencing localised these mutations to non-naive B cells and revealed frequent co-occurrence of drivers in single cells. We found widespread TNFRSF14 biallelic loss in mutant B cells, and several clones with as many as 4-6 driver mutations. Whilst each clone accounts for a small proportion of cells (typically <1%), the myriad mutant clones in each donor collectively amounted to a substantial fraction of B cells harbouring one or more driver mutations. Our results support the hypothesis that somatic mutations in autoimmune lymphocytes may allow them to escape tolerance constraints through a polyclonal cascade of somatic evolution. These findings provide new insights into the molecular basis of autoimmune disease and suggest novel diagnostic and therapeutic avenues.

  Dataset EGAD00001016061

• Polyclonal selection of immune checkpoint mutations in thyroid autoimmunity - PTA_DNAHyb

  Our immune system contains multiple tolerance checkpoints to prevent the activation of self-reactive lymphocytes. How some lymphocytes escape these constraints to cause autoimmune disease remains poorly understood. A long-standing hypothesis in autoimmunity posits that somatic mutations in immune regulatory genes may enable self-reactive lymphocytes to bypass tolerance checkpoints. However, testing this hypothesis has proved challenging due to technical limitations in detecting somatic mutations in polyclonal cell populations. Here, we use deep whole-exome and targeted NanoSeq, a highly accurate single-molecule DNA sequencing protocol, to comprehensively search for driver mutations in autoimmune thyroid disease. This revealed a remarkably high number of B cell clones convergently acquiring loss-of-function somatic mutations in key immune checkpoint genes TNFRSF14 (also known as HVEM) and CD274 (encoding PD-L1), as well as less frequent driver mutations in a diversity of other immune genes. In highly inflamed biopsies, we detected tens to hundreds of independent immune-checkpoint mutant clones. Laser capture microdissection, methylation sequencing, spatial transcriptomics, immunohistochemistry and single-nucleus DNA sequencing localised these mutations to non-naive B cells and revealed frequent co-occurrence of drivers in single cells. We found widespread TNFRSF14 biallelic loss in mutant B cells, and several clones with as many as 4-6 driver mutations. Whilst each clone accounts for a small proportion of cells (typically <1%), the myriad mutant clones in each donor collectively amounted to a substantial fraction of B cells harbouring one or more driver mutations. Our results support the hypothesis that somatic mutations in autoimmune lymphocytes may allow them to escape tolerance constraints through a polyclonal cascade of somatic evolution. These findings provide new insights into the molecular basis of autoimmune disease and suggest novel diagnostic and therapeutic avenues.

  Dataset EGAD00001016062

• Polyclonal selection of immune checkpoint mutations in thyroid autoimmunity - PTA_RNA

  Our immune system contains multiple tolerance checkpoints to prevent the activation of self-reactive lymphocytes. How some lymphocytes escape these constraints to cause autoimmune disease remains poorly understood. A long-standing hypothesis in autoimmunity posits that somatic mutations in immune regulatory genes may enable self-reactive lymphocytes to bypass tolerance checkpoints. However, testing this hypothesis has proved challenging due to technical limitations in detecting somatic mutations in polyclonal cell populations. Here, we use deep whole-exome and targeted NanoSeq, a highly accurate single-molecule DNA sequencing protocol, to comprehensively search for driver mutations in autoimmune thyroid disease. This revealed a remarkably high number of B cell clones convergently acquiring loss-of-function somatic mutations in key immune checkpoint genes TNFRSF14 (also known as HVEM) and CD274 (encoding PD-L1), as well as less frequent driver mutations in a diversity of other immune genes. In highly inflamed biopsies, we detected tens to hundreds of independent immune-checkpoint mutant clones. Laser capture microdissection, methylation sequencing, spatial transcriptomics, immunohistochemistry and single-nucleus DNA sequencing localised these mutations to non-naive B cells and revealed frequent co-occurrence of drivers in single cells. We found widespread TNFRSF14 biallelic loss in mutant B cells, and several clones with as many as 4-6 driver mutations. Whilst each clone accounts for a small proportion of cells (typically <1%), the myriad mutant clones in each donor collectively amounted to a substantial fraction of B cells harbouring one or more driver mutations. Our results support the hypothesis that somatic mutations in autoimmune lymphocytes may allow them to escape tolerance constraints through a polyclonal cascade of somatic evolution. These findings provide new insights into the molecular basis of autoimmune disease and suggest novel diagnostic and therapeutic avenues.

  Dataset EGAD00001016063

• Polyclonal selection of immune checkpoint mutations in thyroid autoimmunity - LCMB_WGS

  Our immune system contains multiple tolerance checkpoints to prevent the activation of self-reactive lymphocytes. How some lymphocytes escape these constraints to cause autoimmune disease remains poorly understood. A long-standing hypothesis in autoimmunity posits that somatic mutations in immune regulatory genes may enable self-reactive lymphocytes to bypass tolerance checkpoints. However, testing this hypothesis has proved challenging due to technical limitations in detecting somatic mutations in polyclonal cell populations. Here, we use deep whole-exome and targeted NanoSeq, a highly accurate single-molecule DNA sequencing protocol, to comprehensively search for driver mutations in autoimmune thyroid disease. This revealed a remarkably high number of B cell clones convergently acquiring loss-of-function somatic mutations in key immune checkpoint genes TNFRSF14 (also known as HVEM) and CD274 (encoding PD-L1), as well as less frequent driver mutations in a diversity of other immune genes. In highly inflamed biopsies, we detected tens to hundreds of independent immune-checkpoint mutant clones. Laser capture microdissection, methylation sequencing, spatial transcriptomics, immunohistochemistry and single-nucleus DNA sequencing localised these mutations to non-naive B cells and revealed frequent co-occurrence of drivers in single cells. We found widespread TNFRSF14 biallelic loss in mutant B cells, and several clones with as many as 4-6 driver mutations. Whilst each clone accounts for a small proportion of cells (typically <1%), the myriad mutant clones in each donor collectively amounted to a substantial fraction of B cells harbouring one or more driver mutations. Our results support the hypothesis that somatic mutations in autoimmune lymphocytes may allow them to escape tolerance constraints through a polyclonal cascade of somatic evolution. These findings provide new insights into the molecular basis of autoimmune disease and suggest novel diagnostic and therapeutic avenues.

  Dataset EGAD00001016064

• Polyclonal selection of immune checkpoint mutations in thyroid autoimmunity - LCMB_WES

  Our immune system contains multiple tolerance checkpoints to prevent the activation of self-reactive lymphocytes. How some lymphocytes escape these constraints to cause autoimmune disease remains poorly understood. A long-standing hypothesis in autoimmunity posits that somatic mutations in immune regulatory genes may enable self-reactive lymphocytes to bypass tolerance checkpoints. However, testing this hypothesis has proved challenging due to technical limitations in detecting somatic mutations in polyclonal cell populations. Here, we use deep whole-exome and targeted NanoSeq, a highly accurate single-molecule DNA sequencing protocol, to comprehensively search for driver mutations in autoimmune thyroid disease. This revealed a remarkably high number of B cell clones convergently acquiring loss-of-function somatic mutations in key immune checkpoint genes TNFRSF14 (also known as HVEM) and CD274 (encoding PD-L1), as well as less frequent driver mutations in a diversity of other immune genes. In highly inflamed biopsies, we detected tens to hundreds of independent immune-checkpoint mutant clones. Laser capture microdissection, methylation sequencing, spatial transcriptomics, immunohistochemistry and single-nucleus DNA sequencing localised these mutations to non-naive B cells and revealed frequent co-occurrence of drivers in single cells. We found widespread TNFRSF14 biallelic loss in mutant B cells, and several clones with as many as 4-6 driver mutations. Whilst each clone accounts for a small proportion of cells (typically <1%), the myriad mutant clones in each donor collectively amounted to a substantial fraction of B cells harbouring one or more driver mutations. Our results support the hypothesis that somatic mutations in autoimmune lymphocytes may allow them to escape tolerance constraints through a polyclonal cascade of somatic evolution. These findings provide new insights into the molecular basis of autoimmune disease and suggest novel diagnostic and therapeutic avenues.

  Dataset EGAD00001016065

• Single individual whole genome sequencing of Jakun, Indigenous Peoples of the Peninsular Malaysia

  This study disected the genetic structure of a Jakun individual, a sub-tribe of Indigenous Proto-Malay from Peninsular Malaysia. They are postulated to have settled in Peninsular Malaysia approximately 4-6 KYA, during the last agricultural expansion. However, their genetic structure is still not well understood.

  Study EGAS50000000740

• The genomic landscape of primary cutaneous anaplastic large cell lymphoma (pcALCL)

  Primary cutaneous anaplastic large cell lymphoma (pcALCL) is the second most common variant of cutaneous T-cell lymphoma. We subjected tumor biopsies from patients with pcALCL to whole-genome sequencing, whole-exome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.

  Study EGAS00001004429

• Space Associated Stem Cell Hallmarks of Aging in Astronauts

  This study examined the effects of the stress of space, specifically low earth orbit, on hematopoietic stem and progenitor cells (HSPCs) that maintain lifelong hematopoiesis and immune responses. Enriched CD34+ HSPCs were derived from 7 astronauts before, during and after 10 and 21-day ISS missions on the International Space Station. The samples were used as input to whole transcriptome sequencing by bulk RNA-Seq performed at The Scripps Research Institute Next Generation Sequencing Core on Illumina NextSeq 2000 sequencer and single cell RNA-Seq performed at The Salk Institute for Biological Studies on Illumina NovaSeq X Plus sequencer. Subsequent expression, RNA editing, and retrotransposon analyses were performed to assess HSPC and immune subpopulation survival dynamics. Overall, these analyses revealed space-associated stem cell hallmarks of aging (SASHA), including spaceflight dependent alterations in HSPC survival and self-renewal, ADAR1, telomere maintenance, mobilization and cell cycle gene expression, combined with space-induced clonal hematopoietic mutations, APOBEC3C activation and retrotransposon deregulation to warrant countermeasure development to enable long-duration spaceflight. Post-spaceflight analysis revealed increased C-to-T and clonal hematopoiesis-associated mutations, repetitive element and base deaminase deregulation, decreased telomere maintenance gene expression, and decreased self-renewal capacity compared to ground controls. These results demonstrate the space-associated aging effects in HSPCs after month-long exposure to LEO, providing insights into utilizing the LEO environment to model space-accelerated aging and other age-related malignancies.

  Study phs004267

• Genomic analysis Nasopharyngeal cancer through whole exome sequencing and whole genomic sequencing.

  Nasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma and has remarkable ethnic and geographic distribution, with a high prevalence in southern China, southeast Asia, northern Africa and Alaska. Although there are previous studies implicated NF-κB pathway play an important role in NPC. Newer research also found several important cellular processes and pathways in NPC, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Put these studies together, although, NPC is still poorly understood at the genetic level. Here we determined the mutational landscape of 553 cases with NPC using whole-genomic and whole-exome sequencing. These approaches revealed a distinct mutational signature and significantly mutated genes.

  Study EGAS00001002788

• High coverage target resequencing of coding and regulatory regions of 38 Parkinson disease genes associated either to the Mendelian or the sporadic forms of the disease

  Coding sequences and putative regulatory sequences (retrieved from Ensembl and including up to 2500 bp of promoter sequence upstream the transcription start site) were re-sequenced to a mean depth of 49X on 38 genes associated to Parkinson's disease (RAB25, NUCKS1, RAB7L1, GBA, SYT11, ACMSD, STK39, MCCC1, STBD1, GAK, DGKQ, BST1, SCARB2, HLA-DRB5, GPNMB, FGF20, ITGA8, HIP1R, STX1B, SETD1A, SREBF1, MED13, RAI1, MAPT, RIT2, GIGYF2, HTRA2, EIF4G1, SNCA, LRRK2, VPS35, PINK1, DJ1, ATP13A2, UCHL1, PARK2, FBXO7, and PLA2G6). Sequencing was performed on 249 Parkinson's idiopathic cases and 145 unrelated controls of Spanish origin. All sequencing data was generated with an Illumina Hiseq2000 instrument after enrichment with a custom NimbleGen array. Raw reads were mapped to human reference genome hg19/GRCh37 using BWA aligner.

  Study EGAS00001000973

• Exome sequences of AL amyloidosis (ALA), multiple myeloma (MM) and ALA+MM hematological malignancies

  DNA was isolated from aberrant plasma cells (aPCs) and peripheral blood of 12 ALA, 10 ALA+MM and 29 MM individuals. DNA from aPCs was amplified using REPLI-g Mini Kit (Qiagen). Totally, we analyzed 51 patients, 102 samples. One batch of exome libraries (paired tumor-normal samples from 12 ALA, 10 ALA+MM and 6 MM) was prepared using SureSelect Human All Exon V5 Kit (Agilent Technologies) and sequenced on Illumina HiSeq 4000 platform, 100 cycles. Second batch (23 MM samples; IDs ARK01-ARK26) was prepared using SureSelect Human All Exon V5 + IGH, IGK, IGL, MYC (Agilent Technologies) library preparation kit and sequenced on Illumina HiSeq 2000 platform in paired-end settings, 75 cycles. The reads were mapped using BWA-MEM on human genome GRCh38 without alternate loci.

  Dataset EGAD00001006047

• 16S-based fecal microbiota composition

  The dataset reports the 16S rRNA gene sequencing of the fecal microbiota of donors from the Milieu Intérieur Cohort. The Milieu Intérieur cohort includes a total of 1,000 healthy individuals of western European ancestry, recruited in France as part of the Milieu Intérieur project. To assess their fecal microbiota composition, 16S rRNA profiles were generated from stool samples of 863 of the 1,000 donors. Human stool samples were produced at home no more than 24 hours before the scheduled medical visit and collected in a double-lined sealable bag maintaining strict anaerobic conditions. Upon reception at the clinical site, the fresh stool samples were aliquoted and stored immediately at -80°C. DNA was extracted from stool and barcoding PCR was carried out using indexed primers targeting the V3-V5 region of the 16S rRNA gene. Equal volumes of normalized PCR reaction were pooled and thoroughly mixed. The amplicon libraries were sequenced on Illumina MiSeq.

  Dataset EGAD00001004979