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• Genomic profiling of localized (lFL) and systemic follicular lymphoma (sFL) reveals novel insights into FL pathogenesis

  At diagnosis, the majority of FL presents with symptomatic disease in advanced/systemic stages of FL (sFL). In contrast only around 10 to 15% of cFL are diagnosed in localized stages (lFL). The biological knowledge is mainly based on data derived from global sFL analysis and only small cohorts of lFL were characterized intensively so far. It is well-known that the hallmark BCL2 translocation is less frequently observed in lFL. Furthermore, lFL differs from sFL concerning their gene expression and their N-glycosylation profiles. In consequence, comprehensive global analysis with CNA profiling and whole exome sequencing was performed in a large cohort of lFL. Additionally, the mutational profile as well as the CNA landscape of lFL and sFL, as well as for BCL2 translocation-positive and -negative was compared.

  Study EGAS00001006927

• The dataset of Southeast Borneo individuals (Banjar and Ngaju ethnic groups) was used as comparative data to determine the Asian parental population of the Malagasy. Our study found strong support for an origin of the Asian ancestry of Malagasy among the Banjar.

  Malagasy genetic diversity results from an exceptional proto-globalisation process that took place over a thousand years ago across the Indian Ocean. Previous efforts to locate the Asian origin of Malagasy have highlighted Borneo broadly as a potential source, but so far no firm source populations have been identified. Here, we have generated genome-wide data from two Southeast Borneo populations, the Banjar and the Ngaju, together with published data compiled from populations across the Indian Ocean region. We find strong support for an origin of the Asian ancestry of Malagasy among the Banjar. This group emerged from the long-standing presence of a Malay Empire trading post in Southeast Borneo, which favoured admixture between the Malay and an autochthonous Borneo group, the Ma’anyan. Reconciling genetic, historical and linguistic data, we show that the Banjar, in Malay-led voyages, were the most probable Asian source among the analysed groups in the founding of the Malagasy gene pool.

  Study EGAS00001001841

• Transcriptomic analysis of metastatic colorectal cancer

  Metastatic colorectal cancer (mCRC) is the main cause of CRC mortality, with limited treatment options. Although immunotherapy has benefited some cancer patients, mCRC typically lacks the molecular features that respond to this treatment. However, recent studies indicate that the immune microenvironment of mCRC may be modified to enhance the effect of immune checkpoint inhibitors. This dataset was used to explore the metastatic immune microenvironment by comparing immune cell populations in colorectal liver (CLM), lung (mLu) and peritoneal (PM) metastases.

  Dataset EGAD50000000926

• International Cancer Proteogenome Consortium (ICPC): Proteogenomics of Early Stage Lung Adenocarcinoma in Taiwan

  Lung cancer in East Asia is characterized by a high percentage of never-smokers with early-onset adenocarcinoma, predominantly with EGFR mutations. To provide an insight into the molecular phenotype of this demographically distinct disease, we have performed a proteogenomics study on a prospectively collected cohort representing early stage lung adenocarcinoma in Taiwan. The distinct mutational profile revealed a high prevalence of the APOBEC mutational signature in early-onset females, implicating differential regulation of APOBEC enzymes and DNA damage pathways, as well as enrichment of mutational signatures congruent with environmental carcinogens over-represented in the genomic location of EGFR. We delineate the proteogenomic hallmarks of tumor progression and propose a proteomics-informed classification that resolves the EGFR mutation heterogeneity associated with survival within the early stages. Functional annotation of the molecular subtypes by protein network analysis highlights candidate biomarkers for patient stratification. Our integrative analysis reveals the molecular architecture of lung cancer in East Asia and enables the path for precision medicine.

  Study phs001954

• Invariant patterns of clonal succession determine specific clinical features of Myelodysplastic syndromes (MDS)

  Myelodysplastic Syndromes (MDS) are heterogeneous myeloid neoplasms, characterized by stepwise acquisitions of multiple somatic mutations. Mutational configurations (e.g. bi-allelic) and specific distributions, timing of acquisitions corresponding to rank within the clonal hierarchy, and combinatorial spectrum are not elucidated. Therefore, we conducted targeted deep sequencing in a panel of the 36 most frequently mutated "myeloid" genes in terms more than of 500 patients with MDS or related myeloid neoplasms.

  Study phs001898

• Multiregional Single-Cell Transcriptomic Analysis of Liver Cancer

  In this study, we performed single-cell transcriptomic profiling of human liver tissues collected from hepatocellular carcinoma and intrahepatic cholangiocarcinoma patients. A total of seven primary liver cancer patients enrolled in this study. Samples were collected from multiple regions, including tumor core, tumor border and adjacent non-tumor tissue. The 10x Genomics platform was used to generate single cell 5' libraries. The Illumina NovaSeq 6000 platform was employed for sequencing.

  Study phs003117

• Whole-exome sequencing of Helicobacter pylori-uninfected normal gastric gland

  Recent studies showed that somatic mutations accumulate in normal tissues with age; however, mutation accumulation in the Helicobacter pylori-uninfected normal gastric mucosa has not been reported. A total of 18 biopsied gastric mucosa were obtained from nine subjects without Helicobacter pylori-infection or gastric cancer. Gastric epithelia were manually dissociated from the lamina propria. Subsequently, single glands were picked up under a stereomicroscope. Genomic DNA isolated from each gland was subjected to whole-exome sequencing.

  Study JGAS000313

• Identification of responsible genes and development of standardized medicine for familial breast cancer by genetic analysis with NGS technology

  Aims: To clarify risk of germline variants of known causal genes for Hereditary Breast Ovarian Cancer Syndrome in Japan by combinatorial analysis of somatic and germline variants in the breast cancer tissue. Methods: Target caputure analysis by using Illumina HiSeq 2000; the panel genes are 119 genes including 30 HBOC known causal genes. Participants/Materials: 108 whole blood and 124 primary tumor samples from familial breast cancer patients.

  Study JGAS000224

• Mechanisms of patient response to Dabrafenib in Melanoma

  Samples will be from the BRF113683 (BREAK-3) study which is a Phase III Randomized, Open-label Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma (n=250 enrolled)*NGS [Agilent capture (Sanger V2 panel): 360 genes and 20 gene fusions; Illumina HiSEQ Sequencing]*CNV: [via NGS or Affy SNP 6.0 or Illumina Omni (TBD)]Bioinformatics: Analysis will be performed using core Sanger informatics pipelines similar to those previously described (Papaemmanuil E et al. (2013) Blood. 22:3616 -3627). Briefly, copy number analysis will be performed using the ASCAT algorithm, and base substitutions, small insertions and deletions using the CAVEMAN and Pindel algorithms, respectively. Statistical approaches including generalized linear models will be used to predict clinical variables such as maximum clinical response and duration of response using genetic data. Sanger and EBI to conduct analysis; Raw data and correlation with clinical endpoints to be analyzed by both EBI/Sanger and GSK (unique pipeline analyses to increase call confidence)

  Dataset EGAD00001001375

• HCA_Female_Reproductive_Adult_WSSS_RNA

  HCA Endometrium_LM The endometrium regenerates monthly and its transformation is executed through dynamic changes in states and interactions of multiple cell types. Using transcriptomics methods we seek to profile changes of the endometrium across the menstrual cycle. Our map will have implications in women’s health and cancer, by enabling the interpretation of GWAS analyses or the studying functional consequences of somatic mutations. 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 EGAS00001004727

• The Northern Manhattan Family Study - a Sub-Study of the Epidemiologic Study of Stroke Outcome in 3 Ethnic Groups: The Northern Manhattan Study

  The Northern Manhattan Family Study is a sub-study of the Northern Manhattan Study (NOMAS), a population-based cohort study investigating stroke and stroke risk factors among individuals from three ethnic groups residing in northern Manhattan. The overall goal for the Northern Manhattan Family Study was to determine the genetic factors associated with stroke precursor phenotypes. A subset of Caribbean Hispanic probands from the NOMAS Study were selected for inclusion in the family study. Selected probands were at high risk for cardiovascular disease, defined as either 1. Having a sibling with a history of myocardial infarction or stroke, or 2. Having two of the following three risk phenotypes above the 75th percentile in NOMAS; maximal carotid plaque thickness, left ventricular mass or homocysteine level. Probands for the family study were enrolled in northern Manhattan and family members were enrolled at two locations: New York at Columbia University and in the Dominican Republic (DR) at the Clinicas Corazones Unidos in Santo Domingo. A subset of Caribbean Hispanic NOMAS participants were included as a replication sample.

  Study phs002406

• Genomic and immune profiling of pre-invasive lung adenocarcinoma

  Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.

  Study EGAS00001004006

• Understand_Paratyphoid_Disease___host_responses_to_human_challenge_with_S__Paratyphi_A

  This project aims to evaluate the transcriptional response to disease measured in whole blood of participants who developed enteric fever after challenge and, importantly, those who were challenged but stayed well throughout the challenge period. This data will provide unique coverage of the transcriptome and will yield invaluable insight after integration with a wealth of clinical data collected during this trial. 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 EGAS00001001260

• Next Generation Sequencing in an IBD Pedigree Whole Genome Data

  In 2009 we identified a four-generation family with over 700 members and 41 affected with Crohn's disease (CD). At the time we sequenced the exome of 6 affected individuals but did not identify any coding variants which appear to explain the high prevalence of disease. Since then we have collected DNA from a large number of additional family members, genotyped linkage arrays on the entire family to refine genomic regions shared by identity by descent and genotyped affected and unaffected members at known CD risk loci identified by Genome Wide Association Studies (GWAS). These analyses have confirmed that a significant unexplained excess of disease remains after accounting for all known genetic factors, and that several regions of the genome are shared by a large fraction of affected individuals. We therefore perform whole genomes sequencing from 8 individuals which will allow us to impute the complete sequence of nearly all the members of the two largest and most severely affected branches of the family.

  Dataset EGAD00001000399

• DAC for the study of response to EGFR Blockade in Colorectal Cancer

  Dac EGAC00001000360

• Mitochondrial Abnormalities in Schizophrenia and Bipolar Disorder

  Mitochondrial DNA structural variation is one proposed indicator of mitochondrial dysfunction. The large common deletion of mitochondrial DNA (mtDNA) increases with aging across multiple brain regions. We found other large deletions of mtDNA in brain at levels comparable to the common deletion (PMID: 30869147). Since mtDNA molecules replicate independently of nuclear division, the mtDNA copy number is a measure of mitochondrial health; levels are negatively correlated with age and all-cause morbidity. Complex I activity is another functional measure of mitochondria. We previously published a subset of this data from DLPFC (PMID: 29594135) for three indicators (common deletion, mtDNA copy number, Complex I activity). For this study, four indicators (common deletion, large deletions, mtDNA copy number, Complex I activity) were measured in four brain regions from subjects with schizophrenia (SZ) and bipolar disorder (BD) and compared to controls. The four brain regions were: the dorsolateral prefrontal cortex, superior temporal gyrus, primary visual cortex (V1), and nucleus accumbens.    

  Study phs002395

• Identification of gene mutations and fusion genes in patients with Sézary Syndrome

  Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma (CTCL) with an aggressive clinical course. The goal of our study is to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sezary cels, fourteen of them fulfilling the diagnostic criteria of SS. Peripheral blood samples were collected for each patient and CD4+ T-lymphocytes and Granulocytes were isolated. DNA and RNA was extracted for matched normal and tumor materials. Whole exome sequencing was performed on matched normal and tumor tissues of 12 patients and RNA sequencing was performed on 10 patients. For 7 of these patients, we have both exome as well as RNA sequencing data. In this study, we present a complex genomic landscape of Sezary syndrome with several point mutations, copy number variations and fusion events which could contribute to the pathogenesis of SS.

  Study EGAS00001001706

• Unrelated Donor Reduced Intensity Bone Marrow Transplant for Children with Severe Sickle Cell Disease (BMT CTN-0601-BioLINCC)

  ObjectivesThe primary objective is to determine event-free survival (EFS) at 1 year after unrelated donor (URD) hematopoietic stem cell transplantation (HCT) using bone marrow (BM) in patients with sickle cell disease (SCD).BackgroundSickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease that can cause organ damage, stroke, and intense pain episodes. Children with sickle cell disease experience organ damage, impaired quality of life, and premature mortality. A blood stem cell transplant is a treatment option for someone with a severe form of the disease. Prior to undergoing a transplant, people typically receive a conditioning regimen of high doses of chemotherapy and other medications to prepare the body to accept the transplant. This type of conditioning regimen is known as a myeloablative conditioning regimen, but it can result in toxicities and sterility. A conditioning regimen that uses lower doses of chemotherapy and medications may be safer for transplant recipients. This type of regimen is known as reduced intensity conditioning (RIC) regimen. RIC has a more favorable toxicity profile but is associated with higher rates of graft rejection (GR), especially with graft sources such as umbilical cord blood This study evaluated the safety and effectiveness of blood stem cell transplants, using bone marrow from unrelated donors, in children with severe SCD who receive a RIC regimen prior to the transplant.SubjectsPatients 3.0-19.75 years old with symptomatic SCD AND one or more of the following complications: (1)-(i) a clinically significant neurologic event (stroke) or any neurologic defect lasting > 24 hours and accompanied by an infarct on cerebral magnetic resonance imaging (MRI); OR, (ii) patients who have a Transcranial Doppler (TCD) velocity that exceeds 200 cm/sec by the non-imaging technique (or TCD measurement of >185 cm/sec by the imaging technique) measured at a minimum of 2 separate occasions one month or more apart; OR, (2) Minimum of two episodes of acute chest syndrome within the preceding 2-year period defined as new pulmonary alveolar consolidation involving at least one complete lung segment (associated with acute symptoms including fever, chest pain, tachypnea, wheezing, rales, or cough that is not attributed to asthma or bronchiolitis) despite adequate supportive care measures; OR, (3) History of 3 or more severe pain events (defined as new onset of pain that lasts for at least 2 hours for which there is no other explanation) per year in the 2 years prior to enrollment despite adequate supportive care measures (if patients are receiving hydroxyurea and compliant with therapy, being symptomatic is an indication for transplantation; however, if patients decline hydroxyurea or non-compliant with this therapy, they would still remain eligible for study if pain criteria as described above are met). Lansky/Karnofsky performance score must be ≥ 40. Hemoglobin S must be ≤ 45%. Patients must have an unrelated adult bone marrow donor who is HLA-matched at 8 of 8 HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Patients with bridging fibrosis or cirrhosis of the liver, with uncontrolled bacterial, viral, or fungal infection in the past month, or seropositivity for HIV are excluded. Patients with HLA-matched family donors, or who have received prior HCT, and females who are pregnant or breast feeding are excluded. Thirty patients were enrolled on this study and of these, 29 patients met the criteria and proceeded to the study transplant.DesignParticipants attended a study visit prior to the transplant to undergo a blood collection, neurocognitive testing to measure learning and brain function, magnetic resonance angiogram (MRA) and magnetic resonance imaging (MRI) scans. Questionnaires to assess quality of life were also completed. All patients received erythrocyte transfusions before transplant. Twenty-two days (-22) before the transplant, participants began receiving a reduced intensity conditioning regimen of chemotherapy and medications. On days -21, -20, and -19 participants weighing 10 kg or more received 10 mg, 15 mg, and then 20 mg of Alemtuzumab intravenously (IV) followed by 30 mg/m2/day IV on days -8 through -4 of Fludarabine. Eight days (-8) before the transplant, participants were admitted to the hospital to continue the conditioning regimen which included 140 mg/m2 IV of Melphalan on day -3. Participants received the bone marrow transplant on day 0. Prophylaxis for GVHD consisted of a calcineurin inhibitor (tacrolimus or cyclosporine) administered from day -3 through day 100 after graft infusion, with subsequent taper through day 180; methotrexate 7.5 mg/m2 on days 1, 3, and 6; and methylprednisolone 1 mg/kg per day from days 7 through 28, with subsequent taper by 20% per week. One week after the transplant continuing until the WBC is normal, participants received granulocyte-colony-stimulating factor (G-CSF). After leaving the hospital, participants attended study visits weekly during weeks 1 to 8, at day 60, weekly during weeks 9 to 14, at Day 100, at month 6, and at years 1 and 2. At all study visits, a blood collection, medical history review, and physical exam occurred. In addition, at day 100, month 6, and years 1 and 2, questionnaires to assess quality of life were completed. At select visits the following procedures were conducted: lung function testing, heart function testing, MRA and MRI scans, and neurocognitive testing.The primary outcome was 1-year EFS. Death, disease recurrence or graft rejection by 1 year were considered events for this endpoint.ConclusionsThe trial met its prespecified 1-year EFS, and significantly improved HRQL was reported posttransplant. However, although the Reduced-intensity conditioning (RIC) provided successful engraftment in most patients, the regimen cannot be considered safe for widespread adoption without modification due to the regimen-related toxicity (RRT) and high rate of chronic GVHD, which was the predominant cause of mortality.

  Study phs003470

• Exome trios in patients with gastroschisis (2019-04-08)

  Gastroschisis (MIM 230750) is a herniation of the intestines through a defect of the abdominal wall lateral to the umbilicus (usually on the right side), and it is not covered by a membrane [Ledbetter, 2012]. Gastroschisis is a congenital anomaly with increasing incidence, easy prenatal diagnosis and extremely variable postnatal outcomes. On the basis of clinical manifestations, epidemiologic charateristics, and the presence and type of additional malformations, gastroschisis could be considered a heterogeneous condition with no gene/s discovered yet. This congenital anomaly affects approximately 1-3 infancts per 10,000 live births [Calzolari et al.1995;Parker et al.,2010] Current knowledge about causative mutations/variants. To date, no single gene has been linked to gastroschisis. Some publications have tried to link this malformation to variants in genes (such as AEBP1 (adipocyte enhancer binding protein) gene [Feldkamp et al,. 2012] or the VEGF-NOS3 pathway [Lammer et al., 2008]. Previously, a Scribble mutant mouse model (circletail) was reported to exhibit gastroschisis, however recent studies demonstrated that the Scribble knockout fetus exhibits exomphalos phenotype of gastroschisis [Carnagham et al., 2013]. 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/ . This dataset contains all the data available for this study on 2019-04-08.

  Dataset EGAD00001004942

• ChIP sequencing for β-catenin and histone modifications in HCC cell lines and organoids with CTNNB1 mutations

  CTNNB1 mutation is a major driver of HCC, particularly in metabolic-associated subtype. This study utilized patient-derived tumour organoids and cell lines harbouring various endogenous CTNNB1 mutations to comprehensively map the transcriptional repertoire regulated by mutant β-catenin through ChIP-seq under normal and fatty conditions. Genome-wide binding patterns of β-catenin were integrated with ChIP-seq data for histone modifications H3K27ac and H3K27me3 to assess active and repressive chromatin states. Oleic acid treatment was used to model fatty conditions.

  Study EGAS50000001274

• cfDNA in Hereditary And High-Risk Malignancies (CHARM)

  Our goal is to improve early cancer detection by developing a blood test to predict cancer development in carriers using circulating DNA. As carriers develop cancer, they may have pre-cancerous cells which release this DNA into the blood (cell-free DNA; cfDNA), which can be detected with novel genetic technologies. We propose to use three complementary cfDNA assays:shallow whole genome sequencing (sWGS), Liquid-Biopsy Sequencing (LB-Seq) and Cell-free Methylated DNA Immunoprecipitation and High-throughput Sequencing (cfMeDip-Seq) for early cancer detection.

  Study EGAS00001006539

• DNA methylation in rhabdomyosarcoma PDX and PDX-derived primary cells

  Conditions to maintain primary tumor cells in culture are largely unknown for most tumor entities including rhabdomyosarcoma. In this collaborative study with Dr. Beat Schäfer's laboratory, we performed DNA methylation profiles of rhabdomyosarcoma patient-derived xenograft (PDX) and their matching PDX-derived primary cells (PPC), where the PPCs were developed and maintained under optimized culture conditions. We further compared DNA methylation profiles between these PDXs and PPCs. Exome sequencing and copy number analysis between these rhabdomyosarcoma PDXs and PPXs were also carried out. These analyses may help us to evaluate a feasibility of in vitro profiling of primary rhabdomyosarcoma cells from a genomic perspective.

  Study phs002051

• SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes [10x]

  CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified non-synonymous mutations in MHC-I restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding, which was associated with a loss of recognition and functional responses by CD8+ T cells isolated from HLA-matched COVID-19 patients. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through sporadically emerging escape mutations in MHC- I restricted viral epitopes.

  Study EGAS00001005060

• Whole Exome Sequences of Human Embryonic Stem Cell Lines

  Human embryonic stem cells (hESCs) are a powerful tool for the study of human development and can form the basis of cellular disease models or therapies. However, the genetic make-up and stability of hESCs has not been systematically studied at a genome-wide level with single nucleotide resolution. We therefore sequenced the whole exomes of widely available hESCs. The data generated has provided new insights about the nature of acquired variation and the genomic integrity of the cell lines. We anticipate that this online resource will enable investigators to access raw sequencing data in order to interrogate cell lines for different disease and trait-associated genetic variants.

  Study phs001343

• Dynamics of tumor ecosystems and microbiome in response to neoadjuvant atezolizumab, bevacizumab, and FOLFOX treatment in patients with unresectable colorectal cancer with liver metastasis

  This study aims to explore the effects of neoadjuvant atezolizumab, bevacizumab, leucovorin, 5-fluorouracil, and oxaliplatin (ABFOLFOX) in patients with unresectable colorectal liver metastases (CRLM), focusing on the molecular dynamics of tumor ecosystems (TE) of CRLM and their impact on treatment outcomes. The study comprises two cohorts with CRLM tissue samples analyzed with RNA sequencing and immunohistochemical staining: cross-sectional cohort A (n = 60, CRLM treated with or without neoadjuvant chemotherapy) and prospective cohort B (n = 20 with serial sampling and treated with ABFOLFOX). Shotgun metagenomic sequencing was done for stool samples from cohort B.

  Study EGAS50000000677

• Next-Generation Sequencing of RNA and DNA Isolated from Paired Fresh-Frozen and Formalin-Fixed Paraffin-Embedded Samples of Human Cancer and Normal Tissue

  Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable resource for clinical research. However, nucleic acids extracted from FFPE tissues are fragmented and chemically modified making them challenging to use in molecular studies. We analysed 23 fresh-frozen (FF), 35 FFPE and 38 paired FF/FFPE specimens, representing six different human tissue types (bladder, prostate and colon carcinoma; liver and colon normal tissue; reactive tonsil) in order to examine the potential use of FFPE samples in next-generation sequencing (NGS) based retrospective and prospective clinical studies. Two methods for DNA and three methods for RNA extraction from FFPE tissues were compared and were found to affect nucleic acid quantity and quality. DNA and RNA from selected FFPE and paired FF/FFPE specimens were used for exome and transcriptome analysis. Preparations of DNA Exome-Seq libraries was more challenging (29.5 % success) than that of RNA-Seq libraries, presumably because of modifications to FFPE tissue-derived DNA. Libraries could still be prepared from RNA isolated from two-decade old FFPE tissues. Data were analysed using the CLC Bio Genomics Workbench and revealed systematic differences between FF and FFPE tissue-derived nucleic acid libraries. In spite of this, pairwise analysis of DNA Exome-Seq data showed concordance for 70-80 % of variants in FF and FFPE samples stored for fewer than three years. RNA-Seq data showed high correlation of expression profiles in FF/FFPE pairs (Pearson Correlations of 0.90 +/- 0.05), irrespective of storage time (up to 244 months) and tissue type. A common set of 1,494 genes was identified with expression profiles that were significantly different between paired FF and FFPE samples irrespective of tissue type. Our results are promising and suggest that NGS can be used to study FFPE specimens in both prospective and retrospective archive-based studies in which FF specimens are not available.

  Study EGAS00001000737

• Somatic mutation rates scale with lifespan across mammals

  The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans. Comparative analyses can shed light on the diversity of mutagenesis across species and on long-standing hypotheses regarding the evolution of somatic mutation rates and their role in cancer and ageing. Here, we used whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found somatic mutagenesis to be dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans, although the relative contribution of each signature varied across species. Remarkably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied displaying a comparable association. Despite widely different life histories among the species surveyed, including ~30-fold variation in lifespan and ~40,000-fold variation in body mass, the somatic mutation burden at the end of lifespan varied only by a factor of ~3. These data unveil common mutational processes across mammals and suggest that somatic mutation rates are evolutionarily constrained and may be a determinant of lifespan.

  Dataset EGAD00001008032

• Enrichment of oral-derived bacteria in inflamed colorectal tumors and distinct associations of Fusobacterium in the mesenchymal subtype

  The association between colorectal cancer (CRC) clinical variables and Fusobacterium, but not other intra-tumoral bacteria, has been extensively studied. Here we leveraged whole-transcriptome sequencing from 807 CRC tumor samples from the AVANT phase III trial to dually characterize tumor gene expression and intra-tumoral bacteria. After stringent filtering, 74 high-confidence taxa were identified. 17 of these species, including 4 Fusobacterium spp., were classified as orally-derived and had a robust signal within right-sided, MSI-H, and BRAF mutant tumors. Across consensus molecular subtypes (CMS), integration of Fusobacterium animalis presence and tumor gene expression revealed that F. animalis had the greatest number of associations in mesenchymal CMS4 tumors, despite an overall lower prevalence than in immune CMS1 tumors. Pathway analysis within CMS4 revealed that F. animalis, but not other highly prevalent species, was uniquely associated with pathways for collagen degradation and formation as well as IL-6 and IL-1 cytokine signaling. These associations could explain in part why Fusobacterium has been previously associated with reduced survival in mesenchymal populations. Overall, this study identified oral-derived bacteria, including Fusobacterium, as broadly more prevalent in inflamed CRC tumors compared to the other subtypes, and the association of intra-tumoral bacteria on tumor gene expression is context- and species-specific.

  Study EGAS00001006757

• hereditary BrEAst Case CONtrol study

  The BEACCON study aimed to address the lack of power of previous studies to identify novel BC predisposition genes by performing extensive sequencing in 12,000 women (11,511 analysed following exclusions) and further enhancing power by using an ‘extreme phenotype’ design with enrichment of familial non-BRCA1 and BRCA2 cases, compared with a control population of older women with ongoing confirmation of cancer-free status at June 2019. Three-quarters of the 1303 candidate genes screened were selected based on empiric evidence from local (69 multi-case BC families) or international whole exome sequencing studies, and the remainder were included to provide detailed coverage of functional pathways with established associations with BC

  Study EGAS00001005043

• Clinical validity of post-surgery circulating tumor DNA (ctDNA) in stage III colon cancer patients treated with adjuvant chemotherapy: the PROVENC3 study

  The PROVENC3 study aimed to determine the clinical validity of post-surgery ctDNA testing in patients with stage III colon cancer treated with adjuvant chemotherapy (ACT). Blood was collected pre-surgery, post-surgery and post-adjuvant chemotherapy. Tumor-informed plasma ctDNA detection was performed through integrated whole genome sequencing (WGS) analyses of formalin-fixed paraffin-embedded tumor tissue DNA (80x), white blood cell germline DNA (40x) and plasma cell-free DNA (30x). These raw WGS data for 209 patients are shared in .cram format in this EGA submission.

  Study EGAS50000000804

• Deciphering the genomic, epigenomic and transcriptomic landscapes of pre-invasive lung cancer lesions to determine prognosis

  Background: Lung carcinoma-in-situ (CIS) lesions are the pre-invasive precursor to lung squamous cell carcinoma. However, only half progress to invasive cancer in three years, while a third spontaneously regress. Whether modern molecular profiling techniques can identify those pre-invasive lesions that will subsequently progress and distinguish them from those that will regress is unknown. Methods: Progressive and regressive CIS lesions were laser-captured and their genome, epigenome and transcriptome interrogated. We analysed 83 progressive lesions, 41 regressive and 33 normal epithelial control samples. DNA methylation and gene expression profiles were further validated using publicly available lung cancer data. Results: Somatic mutation burden was higher in progressive lesions than regressive CIS lesions, across base substitutions, rearrangements, and copy number changes. Driver mutations were present in both progressive and regressive CIS lesions, but were more numerous in progressive cases. Progressive and regressive CIS lesions had distinct epigenomic and transcriptional profiles, with a strong chromosomal instability signature. Gene expression, methylation and copy number profiles can all predict accurately which CIS lesions will progress to lung cancer. Conclusion: Pre-invasive CIS lesions that will subsequently progress to invasive lung cancer can be distinguished from those that will regress using molecular profiling. Progression is associated with a strong chromosomal instability signature. These findings inform the development of novel therapeutic targets.

  Dataset EGAD00001003883

• Deciphering Maternal-Fetal Crosstalk in the Human Placenta During Parturition Using Single-Cell RNA-Sequencing

  Labor is a complex physiological process requiring a well-orchestrated dialogue between the mother and fetus. However, the cellular contributions and communications that facilitate maternal-fetal crosstalk in labor have not been fully elucidated. In this latest version (#5), scRNA-seq was applied to decipher maternal-fetal signaling in the human placenta and chorioamniotic membranes during term labor. Samples were obtained from women who underwent spontaneous labor (n = 24) or who were delivered in the absence of spontaneous labor (n = 18) at term. Samples from previous versions (#1-3) of this study include the placental villous tree, basal plate, and chorioamniotic membranes of women across a range of pregnancy physiologic and pathologic conditions, including the processes of labor (term labor and preterm labor), and COVID-19 (version #3). Version #4 includes samples from the human myometrium during spontaneous term labor.

  Study phs001886

• BipEx_ODonovan_Cardiff

  "BipEx_EGAS000010058452_ODonovan_Cardiff Bipolar Disorder Exomes. This research project was a collaboration between Cardiff University, UK and the Stanley Center at the Broad Institute. In this project we sequenced and analyzed the whole exomes of Bipolar case/control samples from collaborators in UK. Genomic DNA from each sample was sequenced to a mean depth of 20x."

  Dac EGAC50000000130

• BipEx_Craddock_Cardiff

  "BipEx_EGAS00001005845_Craddock_Cardiff Bipolar Disorder Exomes. This research project was a collaboration between Cardiff University, UK and the Stanley Center at the Broad Institute. In this project we sequenced and analyzed the whole exomes of 2,458 Bipolar case/control samples from collaborators in UK. Genomic DNA from each sample was sequenced to a mean depth of 20x."

  Dac EGAC50000000135

• BipEx_Reif_Wurzburg

  "BipEx_EGAS00001005858_Reif_Wurzburg Bipolar Disorder Exomes. This research project was a collaboration between University Hospital Frankfurt and the Stanley Center at the Broad Institute. In this project we sequenced and analyzed the whole exomes of 823 Bipolar case/control samples from collaborators in Germany. Genomic DNA from each sample was sequenced to a mean depth of 20x."

  Dac EGAC50000000145

• BipEx_McQuillin_London

  "BipEx_EGAS00001005851_McQuillin_London Bipolar Disorder Exomes. This research project was a collaboration between University College London, UK and the Stanley Center at the Broad Institute. In this project we sequenced and analyzed the whole exomes of 3,046 Bipolar case/control samples from collaborators in UK. Genomic DNA from each sample was sequenced to a mean depth of 20x."

  Dac EGAC50000000136

• BipEx_Blackwood_Edinburgh

  "BipEx_EGAS00001005843_Blackwood_Edinburgh Bipolar Disorder Exomes. This research project was a collaboration between University of Edinburgh, UK and the Stanley Center at the Broad Institute. In this project we sequenced and analyzed the whole exomes of 932 Bipolar case/control samples from collaborators in UK. Genomic DNA from each sample was sequenced to a mean depth of 20x."

  Dac EGAC50000000134

• BipEx_Corvin_TCD

  BipEx_EGAS00001005844_Corvin_Dublin Bipolar Disorder Exomes. This research project was a collaboration between Trinity College Dublin, Ireland and the Stanley Center at the Broad Institute. In this project we sequenced and analyzed the whole exomes of 191 Bipolar case/control samples from collaborators in Ireland. Genomic DNA from each sample was sequenced to a mean depth of 20x.

  Dac EGAC50000000131

• BipEx_Ouwehand_Cambridge

  "BipEx_EGAS000010058454_Ouwehand_Cambridge Bipolar Disorder Exomes. This research project was a collaboration between Cambridge University, UK and the Stanley Center at the Broad Institute. In this project we sequenced and analyzed the whole exomes of 2,873 Bipolar case/control samples from collaborators in UK. Genomic DNA from each sample was sequenced to a mean depth of 20x."

  Dac EGAC50000000138

• BipEx_Owen_Cardiff

  "BipEx_EGAS000010058455_Owen_Cardiff Bipolar Disorder Exomes. This research project was a collaboration between Cardiff University, UK and the Stanley Center at the Broad Institute. In this project we sequenced and analyzed the whole exomes of 1,106 Bipolar case/control samples from collaborators in UK. Genomic DNA from each sample was sequenced to a mean depth of 20x."

  Dac EGAC50000000139

• BipEx_Adolfsson_Umea

  "BipEx_EGAS00001005842_Umea University Bipolar Disorder Exomes. This research project was a collaboration between Umea University, Sweden and the Stanley Center at the Broad Institute. In this project we sequenced and analyzed the whole exomes of 924 Bipolar case/control samples from collaborators in Sweden. Genomic DNA from each sample was sequenced to a mean depth of 20x."

  Dac EGAC50000000133

• MutWP1: CRUK Grand Challenge Mutographs of Cancer: pancreas (2019-04-03)

  The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. Different patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute (Illumina HiSeqX, 40X and 20X depth respectively). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development. . This dataset contains all the data available for this study on 2019-04-03.

  Dataset EGAD00001004893

• MutWP1: CRUK Grand Challenge Mutographs of Cancer: Colorectal_LCM (2020-02-20)

  The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. Different patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development. . This dataset contains all the data available for this study on 2020-02-20.

  Dataset EGAD00001005994

• Genomic characterization of a patient with AGS and CdLS transcriptomic comparison of his monocytes against healthy and disease control samples

  In this study, we describe an extreme genetic phenotype of two simultaneous genetic lesions, leading to broad alterations in immunophenotype and transcriptome. Whole Exome Sequencing and RNA-Sequencing of CD14+ monocytes was performed on the case patient, and RNA-sequencing was also performed on disease (Systemic Lupus Erythematosus) and healthy controls.

  Study EGAS00001007829

• High-Coverage Whole-Exome Sequencing Identifies Candidate Genes for Suicide in Victims with Major Depressive Disorder

  In this study, we applied an Illumina HighSeq platform-based high-coverage WES technique, which, in addition to the exons, allows the determination of 5′- and 3′-UTRs, promoters to a certain length, along with off-target sequences, such as introns, intergenic regions and infecting viruses. Brains from suicide victims (n = 23; 15 males and eight female) who had suffered from major depressive disorder and from control participants (n = 21; 14 males and seven females) who had died from other causes were used for whole-exome sequencing. Alignment files in bam format were uploaded.

  Dataset EGAD00001004082

• Tourette International Collaborative Genetics (TIC Genetics) Study - NJCTS and NIMH

  The Tourette International Collaborative Genetics (TIC Genetics) Study is an international collaboration of scientists and clinicians specialized in Tourette Disorder (TD) from more than 20 sites across the United States, Europe, and South Korea. The study was established to further our understanding of the genetic architecture of tic disorders by developing a large sample of genotypically and phenotypically well-characterized affected probands and their relatives. We employ state-of-the-art genetic technologies to identify major genetic variants contributing to TD and the most commonly comorbid disorders, such as Obsessive-Compulsive Disorder (OCD) and Attention-Deficit/Hyperactivity Disorder (ADHD). TIC Genetics is a direct result of work of the New Jersey Center for Tourette Syndrome (NJCTS) Sharing Repository (Heiman et. al., 2008; PMID: 19036136), funded by a grant from NJCTS Center of Excellence. Established in 2011 (Dietrich et. al., 2015; PMID: 24771252), the TIC Genetic study focuses on both on familial genetic variants with large effects within multiplex affected pedigrees and on de novo mutations ascertained through the analysis of apparently simplex parent-child trios with non-familial tics. In May 2017, we published a whole-exome sequencing study on apparently 311 parent-child trios (Willsey et. al., 2017; PMID: 28472652). These data, both phenotypes and sequencing data, are available through dbGaP. There were 120 subject samples included in the publication that did not have consent for sharing. These are excluded from dbGaP.In November 2021, we published a whole-exome sequencing study on 13 multiplex TD families (Cao et. al., 2021). These data, both phenotypes and sequencing data, are available through dbGaP.

  Study phs001423

• Establishing stable brain tumor stem cell lines and translational research for new treatments

  Choroid plexus carcinomas (CPCs) have dismal prognoses with limited clinical options. A lack of characterized cell lines has hindered the development of new treatment strategies. Here, we perform whole genome sequencing analyses of two cell lines established from CPCs. Whole genome sequencing (WGS),was performed in CCHE-45 and NGT131 cell lines. Both cell lines harbored pathogenic TP53 point mutations; CCHE-45 additionally displayed TP53 loss. Furthermore, alterations of the NOTCH and WNT pathways were also detected in both cell lines. Two protein-coding gene fusions, BZW2-URGCP, and CTTNBP2-ERBB4, mutations of two oncodrivers, GBP-4 and KRTAP-12-2, and several copy number alterations were observed in CCHE-45, but not NGT131. The discovered difference's importance and implications highlight the possible diversity of choroid plexus carcinoma and call for additional research to fully understand disease pathogenesis. Whole genome sequencing revealed that the two choroid plexus carcinoma cell lines shared TP53 mutations and other common pathway alterations and activation of NOTCH and WNT pathways. Noticeable differences were also observed. These cell lines can serve as valuable models to propose new treatments in these rare but deadly brain tumors.

  Study JGAS000657

• Therapeutic Targeting of Ependymoma as Informed by Oncogenic Enhancer Profiling

  Genomic sequencing has driven precision-based oncology therapy; however, genetic drivers remain unknown or non-targetable for many malignancies, demanding alternative approaches to identify therapeutic leads. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Here, we mapped active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts. Enhancer regions revealed novel oncogenes, molecular targets, and pathways, which when subjected to small molecule inhibitor or shRNA treatment, increased survival and slowed proliferation in mouse and neurosphere patient-derived models of ependymomas. This study represents one of the largest enhancer mapping study of any cancer type to date, and provides a framework for target and drug discovery for other cancers recalcitrant to therapeutic development because of their lack of known genetic drivers.

  Study EGAS00001002696

• Subtyping Sub-Saharan Esophageal Squamous Cell Carcinoma by Comprehensive Molecular Analysis

  Esophageal squamous cell carcinoma (ESCC) occurs as much as 20x more frequently in sub-Saharan Africa than Western countries. Through the UNC-Malawi project collaboration we obtained whole-exome matched tumor/normal and RNA sequencing of 59 ESCC from Malawi between 2011-2012. DNA analysis revealed similar mutations as other cohorts, while RNA analysis revealed three distinct subtypes. Mutational signature analysis revealed a pattern of mutation not previously reported in other cohorts or more broadly. Taken together this suggests the high prevalence of ESCC in the region is secondary to an as yet identified mutagen.

  Study phs001448

• Whole blood RNA sequencing of individuals from Nepal

  This study utilized blood samples collected in Lalitpur, Nepal as part of the Strategic Typhoid Alliance across Africa and Asia (STRATAA) study. The dataset comprises whole blood RNAseq of 376 febrile individuals from Nepal. Blood was collected in PAXgene tubes and sent to Monash University (Melbourne, Australia) where RNA was extracted using the PAXgene Blood RNA kit before being sent to the Wellcome Sanger Institute (Hinxton, UK) for sequencing. Library prep used NEBNext Ultra II RNA custom kits on an Agilent Bravo WS automation platform with poly(A) pulldown. After PCR, plates were purified using Agencourt AMPure XP SPRI beads and libraries were quantified using Biotium Accuclear Ultra high sensitivity dsDNA Quantitative kits. Pooled libraries were normalised to 2.8 nM. Samples were globin depleted using KAPA RNA HyperPrep with RiboErase. Libraries were then subjected to 2x100bp paired-end sequencing on Illumina NovaSeq. Each library was sequenced to an average of 80 million reads. The STRATAA study was approved by the Nepal Health Research Council (NHRC, ref 283 306/2015) and OxTREC (Oxford Tropical Research Ethics Committee, ref 39-15). All participants provided informed consent for human genetic tests.

  Dataset EGAD00001011131

• Parent-of-origin dependent DNA methylation and gene expression in the human placenta

  DNA methylation is globally reprogrammed after fertilization and the parental genomes have similar DNA methylation profiles after implantation except at the germline differentially methylated regions (gDMRs). We, and others, have previously shown that there are a large number of transient gDMRs in human blastocysts, whose differential methylation is lost in embryonic tissues after implantation. In this study we employed genome-wide allelic DNA methylation analyses of highly purified trophoblast cells from human placentas. ~40% of the transient-in-embryo gDMRs maintained their parent-of-origin-dependent biased allelic methylation. RNA sequencing-based allelic expression analyses revealed that some of the placental-specific gDMRs were associated with novel imprinted genes. This approach identified the first examples of X-linked gDMRs specific to the placenta. These findings highlight the unique regulation of allelic DNA methylation in the human placenta, which is important for understanding normal placental development and the pathogenesis of pregnancy complications.

  Study JGAS000038

• 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

• Analysis of Recurrently Protected Genomic Regions in Urine Cell-Free DNA

  This study investigated fragmentation patterns in urine and plasma cell-free DNA and evaluated the relevance of such analysis for cancer diagnostics using urine samples. Specifically, we performed whole-genome sequencing at variable depths and evaluated genome-wide coverage in urine and plasma samples, relative to known genome annotation features. Tumor/germline exome sequencing data included was used to identify genome-wide copy number changes and their effect on cfDNA fragmentation in corresponding genomic regions in urine samples. Data included in this submission is whole-genome sequencing of urine and/or plasma cell-free DNA from healthy volunteers and/or cancer patients, and whole-exome sequencing of tumor DNA and germline DNA (peripheral blood cells) from cancer patients. 

  Study phs002273

• Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls

  We created three technical replicates of cell-free DNA from AML patient plasma to assess batch effects and utility of spike-in controls for the cfMeDIP-seq method. Each set of samples were given to three different technicians with slightly different protocols. Details can be found in Wilson et al. "Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls".

  Dataset EGAD00001006986

• Single-cell profiling maps the spectrum of crosstalk between glioma cells and tumor associated macrophages

  Tumor associated macrophages (TAMs) are a heterogeneous glioma infiltrate, implicated in cancer progression. We performed single-cell RNA-sequencing, to survey TAM response-patterns in glioma.

  Study EGAS00001002185

• TONIC-Trial-cfDNA-Project

  Cell-free DNA (cfDNA) is an emerging technology to predict and monitor response to cancer treatment, including immune checkpoint blockade (ICB). However, data on cfDNA dynamics during ICB in metastatic triple negative breast cancer (mTNBC) are limited. While most applications of cfDNA involve assays that focus on mutation detection, mTNBC and multiple other cancer types are driven by copy number alterations (CNAs). We evaluate cfDNA-based copy number profile abnormality (CPA) score as a potential biomarker for monitoring ICB response in mTNBC, analyzing data from 87 patients enrolled in stage 1 and stage 2 of the TONIC-trial. We find significant concordance between cfDNA-based and tissue-based CNA profiles. Additionally, responders show a decrease in CPA scores upon ICB at week 6 (3 cycles of nivolumab). These findings underscore the potential of cfDNA-based CNA dynamics as a non-invasive biomarker for ICB early response assessment in patients with mTNBC.

  Study EGAS50000001308

• Measles oncolytic virus as an immunotherapy for recurrent/refractory pediatric medulloblastoma and atypical teratoid rhabdoid tumor

  Pediatric recurrent medulloblastoma (MB) and atypical teratoid rhabdoid tumor (ATRT) are largely incurable and warrant novel therapies. We investigated a) the safety of a measles virus variant, MV-NIS, in a pediatric phase 1 study and b) the mechanisms of MV-NIS and potential benefit of combination with immune checkpoint inhibition (ICI). Pediatric patients with recurrent MB or ATRT were treated with intratumoral injections for local recurrence or via lumbar puncture for disseminated recurrence. We evaluated local immune responses to MV-NIS with and without ICI via single-cell and bulk RNA sequencing in an intracranial, immunocompetent, syngeneic murine model. MV-NIS given intratumorally or via repeat intrathecal dosing was safe. MV-NIS prolonged survival in murine models but did not demonstrate additive benefit with ICI. No changes in tumor-infiltrating immune-cell composition or activation were observed in response to MV-NIS treatment; however, MV-NIS induced local expression of neutralizing antibodies, complement cascade, and phagocytosis-related genes.

  Study EGAS50000000811

• Multi-layered molecular characterization defines prognostic subtypes of lung adenocarcinoma in Asian never-smokers

  Multi-layered genomic studies such as the TCGA project have greatly advanced our understanding on molecular pathogenesis of lung cancer. For Asian nonsmoker patients, however, majority of studies have been limited to mutational analyses, emphasizing ethnic differences in driver mutations (e.g. more frequent EGFR mutations and ALK fusions). In essence, a comprehensive multi-layered characterization that could lead to molecular etiology and patient stratification scheme to be translated into clinical applications for this patient group is still missing. Here we report molecular profiling of tumor and matched normal tissues from 114 non-small-cell lung adenocarcinoma patients using whole exome sequencing, transcriptome sequencing, and array comparative genomic hybridization (CGH).

  Study EGAS00001003705

• Evolution and clinical impact of genetic epistasis within EGFR-mutant lung cancers

  The current understanding of tumorigenesis is largely centered on a monogenic driver oncogene model. This paradigm is incompatible with the prevailing clinical experience in most solid malignancies: monotherapy with a drug directed against an individual oncogenic driver typically results in incomplete clinical responses and eventual tumor progression1-7. By profiling the somatic genetic alterations present in over 2,000 cases of lung cancer, the leading cause of cancer mortality worldwide, we show that combinations of functional genetic alterations, i.e. genetic collectives dominate the landscape of advanced-stage disease. We highlight this polygenic landscape and evolution of advanced-stage non-small cell lung cancer (NSCLC) through the spatial-temporal genomic profiling of 7 distinct tumor biopsy specimens and 6 plasma specimens obtained from an EGFR-mutant NSCLC patient at (1) initial diagnosis of early-stage disease, (2) metastatic progression, (3) sequential treatment and resistance to 2 EGFR inhibitors, (4) death. The comprehensive genomic analysis of this case, coupled with circulating free (cf) tumor DNA profiling of additional advanced-stage EGFR-mutant NSCLC clinical cohorts with associated treatment responses uncovered features of evolutionary selection for multiple concurrent gene alterations: including the presence of EGFR inhibitor-sensitive (EGFRL858R;EGFRexon19del) or inhibitor-resistant (EGFRT790M;EGFRC797S) forms of oncogenic EGFR along with cell cycle gene alterations (e.g. in CDK4/6, CCNE1, RB1) and activating alterations in WNT/β-catenin and PI3K pathway genes, which our data suggest can cooperatively impart non-redundant functions to limit EGFR targeted therapy response and/or promote tumor progression. Moreover, evidence of an unanticipated parallel evolution of both EGFR T790M and two distinct forms of oncogenic PIK3CA was observed. Our study provides a large-scale clinical and genetic dataset of advanced-stage EGFR-mutant NSCLC, a rationale for specific polytherapy strategies such as EGFR and CDK4/6 inhibitor co-treatment to potentially enhance clinical outcomes, and prompts a re-evaluation of the prevailing paradigm of monogenic-based molecular stratification for targeted therapy. Instead, our findings highlight an alternative model of genetic collectives that operate through epistasis to drive lung cancer progression and therapy resistance.

  Study EGAS00001002604

• Somatic Genetics of lesions from a POT1 patient (2017-04-27)

  In this project we will use exome sequencing to identify somatic mutations in lesions from a patient with a germline mutation in the protection of telomeres 1 gene (POT1). This dataset contains all the data available for this study on 2017-04-27.

  Dataset EGAD00001003307

• Somatic Genetics of lesions from a POT1 patient (2016-04-20)

  In this project we will use exome sequencing to identify somatic mutations in lesions from a patient with a germline mutation in the protection of telomeres 1 gene (POT1). This dataset contains all the data available for this study on 2016-04-20.

  Dataset EGAD00001002050

• Sequencing Lymphoma

  This repository contains sequencing data to describe the genomic profiles of several B-cell lymphomas including follicular lymphoma and Hodgkin lymphoma. We have used several different high throughput sequencing technologies to interrogate genomic DNA and RNA from tumor cells obtained from lymph node biopsies and normal cells obtained from skin biopsies and peripheral blood mononuclear cells. A number of sequencing platforms for DNA, RNA, and protein were used to generate the data. These platforms include exome sequencing and a custom capture panel (NimbleGen) that targets 7.05 MB corresponding to the exons and splice sites of 1716 genes related to lymphoma biology (WUSM-LP). Other platforms include single-cell RNA-seq and Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), which was used to describe transcriptional and proteomic changes in immune cell subsets within lymphoma patients pre- and post-therapy.

  Study phs001229

• Inherited damaging mutations in immune-related genes favour the development of genetically heterogeneous synchronous colorectal cancer.

  Synchronous colorectal cancers are physically separated tumours that develop simultaneously in the intestine. To understand how common genetic and environmental backgrounds influence the development of multiple tumours, we conduct a genome-wide comparative analysis of somatic alterations of 20 syCRCs from 10 patients. We show that syCRCs have independent genetic origins, acquire discordant somatic alterations, and follow different clonal developments.

  Study EGAS00001001461

• Novel genes for Intellectual Disability identified using whole genome sequence and pathway analysis

  Intellectual Disability (ID) is one of the most common global disorders. However for ~30% of patients with ID no cause is identified, despite a clinical diagnostic odyssey that includes genome wide clinical microarray (CMA). We carefully selected 8 trios, each composed of a child with ID and brain structural defect, and both normal parents for whole genome sequencing (WGS). We conducted WGS on the trio and filtered out de novo single nucleotide variants (SNVs) and then used a pathway-based refinement to select candidates. We confirmed a de novo pathogenic SNV in ARID1B, and likely pathogenic SNVs in CACNB3, SPRY4, PHF6, SQSTM1 and UPF1 in 5 of the 8 children. All genes except ARID1B and PHF6 are previously unreported for ID. We analysed our WGS data using 4 independent algorthims for copy number and structural variation including using de novo whole genome assembly. We confirmed one likely contributory 165kb de novo CNV (missed by CMA). We conducted a validation study of over 2000 exomes for our novel candidate genes and also present a strategy to analyze the non-coding sequence space. This study provides an extensive analysis of WGS in the context of ID and yielded causative variants in >60% of cases.

  Study EGAS00001001386

• Identification of RNA biomarkers in Parkinson's disease patients

  Parkinson?s disease (PD) is an age-related, chronic and progressive neurodegenerative disorder characterized by a loss of dopaminergic neurons and subsequent motor symptoms. These overt motor symptoms are often preceded by prodromal non-motor symptoms. Though a number of genetic and environmental factors have been identified to play a role in PD, more exact methods for both diagnosing and assessing prognosis are yet to be discovered. By analyzing the transcriptome of early-stage PD patients, this study aims to identify genes (including important non-coding RNAs) and pathways altered at disease onset that may be used as novel biomarkers for PD diagnosis as well as potential new drug targets. The study consists of three main sources of data: first year blood transcriptomes, second year blood transcriptome and matched neural stem cell (NSC)/neuron transcriptomes. All transcriptome libraries were synthesized and sequenced using no-amplification non-tagging cap analysis of gene expression (nAnT-iCAGE) on the Illumina HiSeq 2500 platform. Resulting data was mapped to the human genome annotation (hg38), processed CAGE tags were clustered ready for differential expression analyses. First year blood sequencing consisted of 22 PD patients and 10 healthy controls across four lanes. In the second year, a further four lanes were sequenced containing 17 PD patients (12 patients from the first year and 5 new patients) along with 10 healthy controls and 5 first year blood samples matching the new second year patients.

  Study JGAS000119

• Altered Interactions between Circulating and Tissue-Resident CD8 T Cells with the Colonic Mucosa Define Checkpoint Inhibitor Colitis

  Therapeutic immune checkpoint blockade has revolutionized oncology, but treatments are limited by immune-related adverse events, including checkpoint inhibitor colitis (irColitis). To define molecular drivers of irColitis, we profiled ~300,000 cells from the colonic mucosa and blood of 29 patients and controls. Patients with irColitis showed expanded mucosal Tregs (regulatory T cells), CD8 tissue-resident memory T cells expressing CXCL13 and Th17 gene programs, and recirculating ITGB2 CD8 T cells. Cytotoxic CD4 T cells, recirculating CD8 T cells, and endothelial cells expressing hypoxia gene programs were further expanded in colitis associated with anti-PD-1/CTLA-4 compared to in the presence of anti-PD-1 therapy. Luminal epithelial cells in irColitis patients expressed PCSK9, PD-L1, and interferon-induced signatures associated with apoptosis, increased cell turnover, and malabsorption.Raw data files from both colon and PBMCs from irColitis patients and controls have been provided to dbGaP. Count matrices derived from raw RNA-Seq data will be available through GEO accession GSE206301.

  Study phs003418

• Single cell RNA sequencing data in "Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2"

  This dataset includes a total of 5 single cell RNA sequencing (scRNAseq) data of SARS-CoV-2 infected human alveolar stem cell culture models. Two scRNAseq data were obtained from SARS-CoV-2 infection with MOI of 1.0 (1 for control and 1 for infected case) and the other three were obtained from SARS-CoV-2 infection with MOI of 0.1 in the study entitled "Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2". The 10x Chromium Single Cell 3' Reagent kits were used to generate libraries.

  Dataset EGAD00001006242

• Genomic Sequencing of Ewing Sarcoma

  Pediatric Ewing sarcoma is a pediatric cancer that primarily arises from the bone. It is characterized by chimeric fusions of the EWS gene and an ETS family transcription factor. In this study, we performed massively parallel sequencing of a larger collection of Ewing sarcoma tumors to define the genomic landscape of this disease. We found that these tumors are among of the most genetically normal cancers currently characterized. There was also a marked absence of recurrent mutations in immediately targetable signaling transduction pathway genes. In this study we answer outstanding questions about ETS transcription factor expression, effects of treatment on mutational burden in Ewing sarcoma tumors, and describe patterns of tumor evolution. We also found that loss-of-function mutations in STAG2 were present in approximately 15% of Ewing sarcoma tumors and loss of STAG2 expression was associated with disease metastasis in this patient cohort.

  Study phs000804

• Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas

  Pheochromocytomas (PCC) and paragangliomas (PGL) are neural crest-derived tumors. We performed the integrated genomic analysis of a collection of PCC/PGL from the French COMETE network using SNP arrays, whole-exome sequencing, DNA methylation arrays, mRNA expression arrays and miRNA sequencing. We found that PCC/PGL are characterized by a low mutation rate, with few recurrent somatic mutations and focal copy number alterations (CNAs). In contrast, we detected recurrent broad CNAs strongly associated with known molecular groups, often leading to the biallelic inactivation of the known susceptibility genes of PCC/PGL. We also identified DNA methylation changes and miRNA expression clusters strongly associated with molecular groups. Of note, overexpression of the miRNA cluster 182/96/183 is specific of SDHB-mutated tumors and induces invasive traits, whereas silencing of the imprinted DLK1-MEG3 miRNA cluster due to a loss of heterozygosity of the 14q32.2 locus is a potential driver in a subset of sporadic tumors. This comprehensive analysis illustrates the functional interdependence between genomic and epigenomic dysregulations underlying PCC/PGL.

  Study EGAS00001000933

• NICHD Genomic and Proteomic Network for Preterm Birth Research (GPN)

  We performed genome-wide association studies (GWAS) to study the Spontaneous Preterm birth (SPTB). Maternal and neonatal DNA from 743 SPTB (20 to and less than 34 weeks), and 752 controls (39 to and less than 42 weeks) who fully consented for public research usage were collected from participants in several clinical centers in Alabama, Illinois, New York, North Carolina, Rhode Island, Texas, and Utah. Cases were 1:1-matched with controls according to race/ethnicity (White, Hispanics, African Americans, and Others), maternal age (<20, 20-29, 30-39, 40+), and parity (yes or no). To determine the case-control status for each participant, a Gestational Age (GA) was determined. DNA samples were taken from blood or saliva if blood was not available. Automated DNA extractions were performed on the Qiagen M48 robot, and samples were organized in 96-well plates with barcoding and sample tracking systems. Subsequent manipulations were performed on the Biomek FX liquid handling workstation with 96-channel pipetting. DNA quantitation was performed by dye-based assay on a Molecular Devices SpectraMax Plus plate reader. Samples were genotyped using Affymetrix Genome-Wide Human SNP Array 6.0. This work was conducted at the Microarray Facility at the University of Pennsylvania. Patient data were collected through chart reviews and patient interviews, which included Demographic information (parental age, race, ethnicity, etc.); Medical history (pre-pregnancy weight, height, medications, STD history, medical conditions, etc.); Social history (marital status, years of education, alcohol use and tobacco use); Obstetrical history including outcome of all prior pregnancies and dates of termination; History of preterm labor or premature rupture of membranes symptoms, evaluation or hospitalization for those symptoms in current pregnancy; Medications taken during current pregnancy; History of cervical evaluation (manually or ultrasonographically) or fetal fibronectin measurements; Pregnancy complications; Labor (type, indications, membrane status, and induction method); Delivery type and indications for cesarean section; Neonatal outcome (sex, weight, length, Apgar score, neonatal complications, admission to intensive care unit, etc.); and Maternal family history of SPTB.

  Study phs000714

• Large Scale Genotyping of Psychiatric Disorders

  Psychiatric disorders cause enormous human suffering and cost to society. The goal of this project is to elucidate the genetics of psychiatric disorders through a large consortium effort and genome-wide genotyping. The Psychiatric Genomics Consortium (PGC) (https://www.med.unc.edu/pgc) is an international consortium to pursue genome-wide analyses of common psychiatric disease. The PGC was founded in 2007 to unite investigators from around the world to conduct mega-analyses of individual genome-wide genotype data for schizophrenia (SCZ), bipolar disorder (BIP), autism (AUT), attention-deficit hyperactivity disorder (ADHD), and major depressive disorder (MDD). Subsequently, the PGC has expanded to include Tourette syndrome (TS), obsessive-compulsive disorder (OCD), eating disorders (ED), post-traumatic stress disorder (PTSD), and substance abuse (SUD). The PGC partnered with Illumina to develop the PsychChip, a custom GWAS array aimed at capturing common variation genome-wide for imputation, rare coding variation drawn from the exome chip and dense genotypes for loci with suggestive evidence for association across the initial PGC analyses of SCZ, MDD, BPD, ASD and ADHD. Samples (cases, controls, and families) were collected from Institutional Review Board-approved protocols that aim to study the genetics of psychiatric disorders. Genome-wide genotyping was performed at the Broad Institute (Cambridge, MA, USA) and the Mount Sinai School of Medicine Friedman Brain Institute (New York, NY, USA) using the PsychChip or Exome Chip.

  Study phs001413

• Peripheral blood RNA-sequencing in 4,732 participants of the INTERVAL cohort

  We performed bulk RNA-sequencing on peripheral blood collected from 4,732 blood donors recruited as part of the INTERVAL study. Using these data, we mapped gene expression and splicing quantitative trait loci (QTLs). Then, we integrated these data with protein, metabolite and lipid QTLs in the same individuals. The study aimed to identify the shared genetic etiology across transcriptional phenotypes, molecular traits and health outcomes in humans.

  Dataset EGAD00001008015

• Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4

  Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT patients in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors, but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.

  Dataset EGAD00001000850

• Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4

  Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT patients in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors, but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.

  Dataset EGAD00001000794

• Molecular and cellular composition changes after neoadjuvant letrozole and palbociclib in early luminal breast cancer

  The NeoPAL trial compared neoadjuvant letrozole-palbociclib (LP) with chemotherapy (CT) in 103 patients with high-risk early luminal breast cancer. Deconvolution of bulk RNA-seq data revealed that myoepithelial cells, normal-like fibroblasts, FOLR2+ macrophages and SELL+ CD4+ T lymphocytes accumulated after treatment (p: 0.046 to 7.2e-07). All changes were similar between the LP and CT arms.

  Study EGAS50000001021

• Microenvironment subtypes and association with tumor cell mutations and antigen expression in follicular lymphoma

  Follicular lymphoma (FL) is a B-cell lymphoma with a complex tumor microenvironment that is rich in non-malignant immune cells. We applied single-cell RNA-sequencing to characterize the immune microenvironment of FL. This provides a classification framework of the FL microenvironment, their association with FL genotypes and antigen presentation, and informs different potential immunotherapeutic strategies.

  Study EGAS00001006052

• Human papillomavirus integration induces oncogenic host gene fusions in oropharyngeal cancers

  HPV integration disrupts host genomic structure and expression, but whether these alterations promote cancer development remains unclear. Multiple genomic analyses of oropharyngeal cancers identified several host gene fusions, including recurrent FGFR3-TACC3 fusions, expressed from rearranged genomic loci adjacent to HPV integration sites. Evolutionary modeling implicated integration of virus concatemers into the host genome as a common initiating event in fusion formation. Co-expression of HPV16 E6/E7 and FGFR3-TACC3, but neither alone, was sufficient for tumor development in both xenograft and syngeneic mouse models and led to unique transcriptional programs implicated in carcinogenesis. FGFR3-TACC3 expression decreased the ubiquitination and degradation of E6 and E7, thereby increasing oncoprotein abundance. We conclude that expression of HPV16 oncoproteins and host gene fusions generated from HPV integration sites can be sufficient for cancer development.

  Study EGAS50000000892

• Convergent somatic evolution from early life in a germline ribosomopathy

  Clonal tracking of stem cells and their progeny by whole genome sequencing permits exploration of evolutionary genetics in human disease. In this study, we performed phylogenetic reconstruction of haematopoiesis using somatically acquired mutations in 323 single haematopoietic stem and progenitor cell-derived colonies from 10 individuals with an inherited disorder of ribosome assembly, Shwachman-Diamond syndrome. We observed numerous clonal expansions, with recurrent acquisition of mutually exclusive mutations (EIF6, TP53, RPL5, RPL22, PRPF8, chromosomes 7 and 15) in multiple different clones in utero or early childhood converging on the p53-dependent nucleolar surveillance pathway that monitors ribosome integrity. In contrast to clones carrying biallelic TP53 mutations, genomes derived from colonies carrying mono-allelic TP53 mutations displayed no increase in mutation burden or specific mutational signatures. Our study highlights striking loss of clonal diversity with convergent somatic evolution on the p53-dependent nucleolar surveillance pathway from early life to offset the deleterious effects of a germline mutation in a Mendelian haematopoietic disorder.

  Dataset EGAD00001009061

• Single cell chromatin accessibility allows analysis of the transposable element landscape, revealing shared features of immune tissue-residency

  Tissue adaptation is required for regulatory T (Treg) cells to function within organs. Whether this program shares similarities between different tissue-localized immune populations is poorly understood. Here, we addressed this by analyzing single-cell chromatin accessibility data, including the transposable element (TE) landscape, of CD45+ immune cells from different tissues. We identified features of organ-specific tissue adaptation across different immune cells. Focusing on tissue-Treg cells, we found that the Treg tissue adaptation program was conserved in other tissue-localized immune cells, such as amphiregulin-producing Th17 cells. Accessible TEs can act as regulatory elements but their contribution to tissue adaptation is unclear. TE landscape analysis revealed an enrichment of specific transcription factor binding motifs in TE regions within accessible chromatin peaks. TEs, specifically from the LTR family, were located in enhancer regions and associated with tissue adaptation. These findings broaden our understanding of immune tissue-residency, an important step towards organ-specific immune interventions.

  Study EGAS50000000350

• Targeted sequencing of candidate regions on chromosome 22q predisposing to multiple schwannomas

  Constitutional LZTR1 or SMARCB1 pathogenic variants have been found in ~86% of familial and ~40% of sporadic schwannomatosis cases. Hence, we performed massively parallel sequencing of the entire LZTR1, SMARCB1 and NF2 genomic loci in 35 individuals with schwannomas negative for constitutional first-hit pathogenic variants in the LZTR1/SMARCB1/NF2 coding sequences, however with 22q deletion and/or a different NF2 pathogenic variant in each tumor, including six cases with only one tumor available. Furthermore, we verified whether any other LZTR1/SMARCB1/NF2 (likely) pathogenic variant(s) could be found in 16 cases carrying a SMARCB1 constitutional variant in the 3’ untranslated region (3’-UTR) c.*17C>T, c.*70C>T or c.*82C>T. As no additional variants were found, functional studies were performed to clarify the effect of these 3’-UTR variants on the transcript. The 3’-UTR variants c.*17C>T and c.*82C>T showed pathogenicity by negatively affecting SMARCB1 transcript level. Two novel deep intronic SMARCB1 variants, c.500+883T>G and c.500+887G>A, resulting in out-of-frame missplicing of intron 4, were identified in two unrelated individuals. Further resequencing of the entire repeat - masked genomics sequences of chromosome 22q in individuals negative for pathogenic variants in the SMARCB1/LZTR1/NF2 coding- and non-coding regions revealed five potential schwannomatosis-predisposing candidate genes, i.e. MYO18B, NEFH, SGSM1, SGSM3 and SBF1, pending further verification.

  Study EGAS00001005680

• WGS of human colorectal cancer organoid exposed to genotoxic pks+ E. coli

  Organoid cultures were exposed to different E.Coli strains and a dye control. In total 25 organoid cultures were whole-genome sequenced using the Novaseq6000 platforms. The data is deposited as .bam format.

  Dataset EGAD50000000304

• Tumor mutational landscape in individuals with CMMRD

  Whole exome sequencing data from the tumors (n=16) of individuals with constitutional mismatch repair deficiency. Data was aligned to GRCh38.

  Study EGAS50000000081

• miRNA

  miRNA Sequencing of olfactory mucosa (OM) cells derived from cognitively healthy and individuals with AD exposed to traffic-related ultrafine particles (UFPs) for 72h in submerged cultures. The UFPs used for exposures were: A0 and A20. Exposures were compared to the corresponding blank samples.

  Dataset EGAD50000001532

• Whole-exome-sequencing in Motor neuron disease (MND)

  To identify the genetic cause and modifiers of Motor neuron disease (MND), we performed Whole-exome-sequencing of Motor neuron disease (MND) patients.

  Study JGAS000422

• Whole-genome-sequencing and Whole-exome-sequencing in Myopathy

  To identify the genetic cause and modifiers of Myopathy, we performed Whole-genome-sequencing and Whole-exome-sequencing of Myopathy patients.

  Study JGAS000365

• Whole-exome-sequencing in Charcot-Marie-Tooth disease (CMT)

  To identify the genetic cause and modifiers of Charcot-Marie-Tooth disease (CMT), we performed Whole-exome-sequencing of CMT patients.

  Study JGAS000337

• Department of Human Genetics at Yokohama City University (YCU) — Data Access Committee

  The Data Access Committee at Yokohama City University (Department of Human Genetics) is overseeing controlled access to data for our research manuscripts. Access is granted to bona fide researchers in line with the Data Access Agreement and DUO restrictions.

  Dac EGAC50000000770

• Fungal infection in neural tissue from Amyotrophic Lateral Sclerosis

  The study shows that fungus infection, isolated from neural tissue, can be a risk factor to develop Amyothophic lateral sclerosis (ALS).

  Study EGAS00001002473

• Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer Genome-Wide Association Study (GWAS) - Primary Scan (Stage 1) - PLCO Screening Trial

  The Cancer Genetic Markers of Susceptibility (CGEMS) prostate cancer genome-wide association study (GWAS) included genotyping approximately 550,000 SNPs (Phase 1A with HumanHap300 and Phase 1B HumanHap240, both from Illumina, San Diego, CA) in 1,172 prostate cancer patients and 1,157 controls of European ancestry from the Prostate, Lung, Colon and Ovarian (PLCO, http://www.cancer.gov/prevention/plco/) Cancer Screening Trial. The original analysis published in Nature Genetics [PMID: 17401363] included 2,282 subjects. After improvement and revisions of the original analysis, 2,252 subjects were submitted to dbGaP.

  Study phs000207

• Genomic and Transcriptomic Landscape of Fibrolamellar Hepatocellular Carcinoma

  Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare liver tumor primarily affecting adolescents and young adults. Little is known of the molecular pathogenesis. To characterize the disease we performed RNA sequencing and whole genome sequencing on FL-HCC tumors and adjacent normal tissue. The results demonstrate few consistent differences on the chromosomal level and many hundreds of alterations in the expression of RNA transcripts.

  Study phs000709

• Large Cancer Fingerprint Screening for Detection of Minimal Residual Disease.

  We describe an approach for large cancer fingerprint screening and its application to cell-free DNA from patients with cancer. Our approach involves tracking somatic mutations identified from patients' tumor biopsies, in the cell-free DNA from a blood draw.

  Study phs001977

• smallRNA-seq of isolated pancreatic islets

  In this study we performed smallRNA-sequencing, a sequencing method designed for small noncoding RNAs, to investigate the miRNA expression profile of human islets isolated from pancreata of donors without diabetes mellitus (n=3) and donors with type 2 diabetes (n=3).

  Study EGAS50000000865

• 3' mRNA- sequencing bams

  This project stores bam files from 3'RNA-seq from oesophageal adenocarcinoma at different timepoints during neoadjuvant treatment (prior, during, post treatment), which were used to analyse evolutionary and phenotype dynamics in oesophageal adenocarcinoma. Samples were collected within the clinical MEMORI trial.

  Study EGAS50000000242

• Somatic L1 retrotransposition mapping in high-grade serous ovarian carcinoma using LDI-PCR/Nanopore-sequencing

  Somatic L1 retrotransposition was mapped in high-grade serous carcinoma (HGSC) tumors using LDI-PCR/Nanopore-seq method. This method identifies somatic L1 insertions originating from two active L1 loci at chr22q12.1 and chrXp22.2. Multiple tumors from the same patient were utilised to understand L1-mediated intrapatient heterogeneity. Long-read data generated by LDI-Nanopore sequencing was aligned to the reference genome (GRCh38).

  Dataset EGAD50000001707

• Whole genome sequencing, DNA methylation, and gene expression data from gastrointestinal stromal tumor 30 patients

  We performed WGS along with genome-wide DNA methylation and gene expression analyses in 30 GIST cases to determine the genomic and epigenomic differences between KIT exon 11 557���558 deletions and other KIT exon 11 mutations.

  Study JGAS000604

• NeoRhea Bulk RNA and Single nuclei RNA & ATAC

  The aim of this study is to compare baseline and surgery samples of ER+/HER2- early breast cancer patients. Patients have been treated with endocrine therapy in combination with palbociclib. Samples have been collected pre and post treatment.

  Study EGAS50000001403

• HER2_positive_Breast_Cancer_

  We propose to definitively characterise the somatic genetics of HER2+ve breast cancer through generation of comprehensive catalogues of somatic mutations in a number of cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.

  Study EGAS00001000042

• Triple_Negative_Breast_Cancer_sequencing

  We propose to definitively characterise the somatic genetics of triple-ve breast cancer through generation of comprehensive catalogues of somatic mutations in a number of cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.

  Study EGAS00001000161

• Single-cell RNA sequencing of cytokine-induced T cell responses

  Cytokines affect T cell responses by polarising them to different phenotypes. We isolated T cells from healthy platelet donors and cultured them in resting and stimulated condition, as well as in the presence of Th2, iTreg and Th17 polarizing cocktail. To characterize the efficacy of cytokine induced porization and subpopulation specific response, we profiled single cell transcriptome five days following polarization using 10x platform (3' v2).

  Dataset EGAD00001005290

• Longitudinal analysis of treatment induced genomic alterations in gliomas

  Here, we report the longitudinal whole exome sequencing analysis of a patient with a primary GBM and two recurrences, demonstrating the heterogeneity caused by the therapy induced molecular changes and their implications for clinical decision-making. This analysis revealed the impact of temporal evolution for tumors under the pressure of treatment. We presented that while targeted treatments eliminated some sensitive clones, there were clones that were enriched leading to resistance. This study demonstrates the importance of longitudinal genomic profiling to adjust to the dynamic nature of therapy induced molecular changes to improve the outcomes of precision therapies.

  Study EGAS00001002168