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• Genomic profiling for metastatic uveal melanoma from a phase I study of the protein kinase C inhibitor AEB071

  Up to 50% of patients with uveal melanoma (UM) develop metastatic disease, for which there is no effective systemic treatment. This study aimed to evaluate the safety and efficacy of the orally available protein kinase C inhibitor, AEB071, in patients with metastatic UM, and to perform genomic profiling of metastatic tumor samples, with the aim to propose combination therapies. Metastatic UM patients (n=153) were treated with AEB071 in a Phase I, single-arm study. Patients received total daily doses of AEB071 ranging from 450 to 1400 mg. First-cycle dose-limiting toxicities (DLTs) were observed in 13 patients (13%). These were most commonly gastrointestinal system toxicities and were dose related, occurring at doses > 700 mg/day. Preliminary clinical activity was observed, with 3% of patients achieving a partial response and 50% with stable disease (median duration 15 weeks). High-depth, targeted next-generation DNA sequencing (NGS) was performed on 89 metastatic tumor biopsy samples. Mutations previously identified in UM were observed, including mutations in GNAQ, GNA11, BAP1, SF3B1, PLCB4, and amplification of chromosome arm 8q. GNAQ/GNA11 mutations were observed at a similar frequency (93%) as previously reported, confirming a therapeutic window for inhibition of the downstream effector PKC in metastatic UM. In conclusion, the protein kinase C inhibitor AEB071 was well tolerated and modest clinical activity was observed in metastatic UM. The genomic findings were consistent with previous reports in primary UM. Together, our data allow envisaging combination therapies of PKC inhibitors with other compounds in metastatic UM.

  Study phs001953

• Rare Diseases Clinical Research Network (RDCRN) Vasculitis Clinical Research Consortium (VCRC) Longitudinal Protocol for Polyarteritis Nodosa

  The development and validation of accurate biological markers and predictors of disease activity and outcome in Polyarteritis Nodosa (PAN), a form a idiopathic vasculitis, would have a major positive impact on the clinical care of patients with this rare disease, be an important advance in the design of clinical trials and feasibility of new drug development, and provide important insight into the pathogenesis of this condition. Current measures of disease activity, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), while helpful in selected settings, are mostly considered highly flawed and markers whose poor correlation with disease flares makes them inadequate to help guide therapy. Similarly, ESR and CRP are clearly unhelpful as diagnostic tests for vasculitis. The current state of clinical investigation for vasculitis relies heavily upon determination of disease status solely by clinical presentation and investigator opinion. Thus, discovery and validation of more precise markers that quantifiably measure activity, predict disease course, and correlate with an important biological process, would be of great importance. Knowledge to be gained from this study could potentially be highly important. Discovery of effective biomarkers of vasculitis and assessment of long term disease course and complications by the collection of clinical and diagnostic imaging studies proposed could lead to better care and less toxic treatment regimens. Furthermore, insight into the pathophysiology of vasculitis could be gained and this might lead to better treatments and improved outcomes in terms of reduction of vascular and treatment related complications. Ideally, excellent biomarkers reflect a sophisticated understanding of the pathophysiology of a disease.

  Study phs000590

• A Machine Learning Tool Integrating Circulating Cell-Free DNA Methylation with Clinical Variables for Non-Invasive Diagnosis of Liver Graft Pathology

  Liver Transplant Recipients (LTRs) with elevated liver enzymes can develop graft injury due to various etiologies, such as T-cell mediated rejection (TCMR) and NASH (NASH-LT). While liver biopsy is the gold standard method for diagnosis of graft pathology, it is invasive and is associated with risks. The goal of our study was to develop a Machine Learning (ML) tool integrating clinical variables with methylation patterns on circulating DNA in plasma as a non-invasive diagnostic tool of graft injury. We generated methylation profiles of circulating DNA in a pilot study of 43 LTRs (11 NASH-LT, 19 TCMR, and 13 Control-LT), and developed an L2 multinomial logistic regression ML approach across 101 bootstrapped models to distinguish between the graft conditions. NASH was associated with distinctive methylation patterns on genes involved in fatty acid metabolism, while methylation of platelet-derived growth factors was identified in patients with TCMR. Our ML model achieved a mean multi-classification accuracy of 0.91, with mean specificity and sensitivity of 0.94 and 0.91, respectively. The model was found to be particularly adept at detecting TCMR and Control-LT, with true positive rates (TPRs) of 95% and 90%, and areas under the curve (AUROC) of 0.992 and 0.985, respectively. For NASH-LT, the models achieved a performance with a TPR of 82% and an AUROC of 0.991. These preliminary results suggest that our newly developed ML tool, leveraging cell-free DNA methylation and clinical variables, is a promising non-invasive classifier of graft pathology.

  Study EGAS00001007171

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

  iTHER is a prospective national precision oncology program aiming to define tumor molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory pediatric tumors in order to identify relevant aberrations to inform treatment. From April 2017 to April 2021, 302 samples of 253 patients were included. Comprehensive molecular profiling utilizing lcWGS, WES, RNAseq, Affymetrix, and/or 850k methylation profiling was performed for 226 samples. Germline pathogenic variants were identified in 16% of patients. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with priority levels very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%). Diagnosis was revised or refined in 8 patients (3.5%). Spatial and temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analysis. Of 137 patients with follow-up beyond 12 months, 21 molecularly matched treatments were applied in 19 patients (13.9%) with modest response. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates feasibility of comprehensive molecular profiling across all ages, tumor types and stages in pediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants within a clinically relevant timeframe. Therefore, WES and RNAseq is implemented into standard clinical care at the Princess Máxima Center for all children. Improved access to targeted treatments within biology-driven combination trials is required to eventually improve survival.

  Study EGAS00001007099

• Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses

  Background Single-cell RNA sequencing (scRNAseq) is a powerful tool for studying complex biological systems, such as tumour heterogeneity and tissue microenvironments. However, the sources of technical and biological variation in primary solid tumour tissues and patient-derived mouse xenografts for scRNAseq, are not well understood. Here, we used low temperature (6°C) protease and collagenase (37°C) to identify the transcriptional signatures associated with tissue dissociation across a diverse scRNAseq dataset comprising 128,481 cells from patient cancer tissues, patient-derived breast cancer xenografts and cancer cell lines.Results We observe substantial variation in standard quality control (QC) metrics of cell viability across conditions and tissues. From FACS sorted populations gated for cell viability, we identify a sub-population of dead cells that would pass standard data filtering practices, and quantify the extent to which their transcriptomes differ from live cells. We identify a further subpopulation of transcriptomically “dying” cells that exhibit up-regulation of MHC class I transcripts, in contrast with live and fully dead cells. From the contrast between tissue protease dissociation at 37°C or 6°C, we observe that collagenase digestion results in a stress response. We derive a core gene set of 512 heat shock and stress response genes, including FOS and JUN, induced by collagenase (37°C), which are minimized by dissociation with a cold active protease (6°C). While induction of these genes was highly conserved across all cell types, cell type-specific responses to collagenase digestion were observed in patient tissues. We observe that the yield of cancer and non-cancer cell types varies between tissues and dissociation methods.Conclusions The method and conditions of tumour dissociation influence cell yield and transcriptome state and are both tissue and cell type dependent. Interpretation of stress pathway expression differences in cancer single cell studies, including components of surface immune recognition such as MHC class I, may be especially confounded. We define a core set of 512 genes that can assist with identification of such effects in dissociated scRNA-seq experiments.

  Study EGAS00001003753

• Multi-Site Collaborative Study for Genotype-Phenotype Associations in Alzheimer's disease and Longitudinal follow-up of Genotype-Phenotype Associations in Alzheimer's disease and Neuroimaging component of Genotype-Phenotype Associations in Alzheimer's disease

  GenADA is a multi-site collaborative study, involving GlaxoSmithKline Inc and nine medical centres in Canada, to develop a dataset containing 1000 Alzheimer's disease patients and 1000 ethnically-matched controls in order to associate DNA sequence (allelic) variations in candidate genes with Alzheimer's disease phenotypes. The study consists of both retrospective and prospective components, that is, patients with an existing diagnosis of Alzheimer's disease as well as newly diagnosed patients were enrolled in the study. Thus, clinical data was retrospectively or prospectively obtained on Day 1 of entry into GenADA. Where possible, biological relatives with Alzheimer's (up to third degree relationship such as cousins) and unaffected siblings of AD cases were also recruited. Note that recruitment numbers for biological relatives were lower than expected and genotypic data has not been submitted to dbGap for these subjects. The purpose of this study is: To identify DNA sequence variations (genotype) in candidate genes that are associated with the clinical symptoms and behavioural features of Alzheimer's disease (phenotype), which differ between study participants with and without the disease. To identify other genotype-phenotype associations in cognitively impaired study participants such as age of onset, family history, rate of cognitive decline, patterns of behavioural/psychiatric non-cognitive symptoms factors, response to treatment co-morbid conditions, and risks/exposure. The final subject recruitment for this study included 875 Alzheimer's disease patients, 850 ethnically-matched controls, and 37 family members. GenADA LONG is a longitudinal assessment to the original GenADA study. Eligible subjects were recruited from five of the nine memory clinics that participated in the GenADA study. Mild to moderate AD participants, a matched subset of controls, and biological related siblings (both affected and unaffected) or other blood relatives affected with AD, were initially examined a minimum of 12 months from recruitment into the original GenADA study, then at two further intervals of 12 and 18 months after time of entry into GenADA LONG. This enables an evaluation of the disease progression in AD patients and a determination of whether controls show evidence of cognitive decline. The overall goal of this extension study is to identify genetic differences and environmental influences that modulate the age of onset of the disease, the course of the disease, and/or biomarkers for neurodegenerative processes. Three of the five memory clinics that participated in the GenADA LONG study recruited eligible patients into GenADA Imaging. A concurrent neuroimaging sub-study was conducted at three of the five memory clinics participating in GenADA LONG. Eligible AD cases with mild to moderate AD, who were recruited into the original GenADA study and participated in the GenADA LONG extension study, were enrolled. Additionally, controls that showed signs of cognitive decline, as part of the assessment in GenADA LONG, were imaged at baseline, 12 and 18 month scanning intervals. The objective of this study is to find genes that: affect changes in AD brain volume measure by magnetic resonance in order to investigate how well change in brain volume predicts other key clinical measures in AD, such as neurodegenerative scales; that correlate changes in brain volume for other genotype-phenotype associations in cognitively impaired study participants; and that correlate with other clinically applicable magnetic resonance measures of pathology that can be conducted at the same time as structural volume measures, and are complementary to the volume measures. The ultimate aim of this research is to obtain a better understanding and definition of Alzheimer's Disease in order to develop new improved medicines.

  Study phs000219

• Prematurity and Respiratory Outcomes Program (PROP) Core Database Protocol (PROP-BioLINCC)

  Data Access NOTE: Please refer to the "Authorized Access" section below for information about how access to the data from this accession differs from many other dbGaP accessions. Objectives: The Prematurity and Respiratory Outcomes Program (PROP) was performed to identify suitable predictors of respiratory outcomes that may serve as surrogate endpoints in future trials of prevention and therapy of respiratory diseases in preterm infants.Background: Acute and chronic respiratory morbidities are common in premature births, and can pose significant risk to the infant's health, particularly during the first two years of life. One such condition is bronchopulmonary dysplasia (BPD) where infants require oxygen therapy due to abnormal repair and impaired lung development after acute lung injury. BPD poses a high mortality risk, even in infants that survive the initial hospitalization. Regardless of BPD diagnosis, preterm infants frequently return for medical care due to symptoms of post-prematurity respiratory disease (PRD), which includes intermittent or chronic wheezing, cough without cold, poor growth, apnea and cyanosis, and lower respiratory tract infections. Impaired lung function can persist into adulthood, contributing to chronic respiratory diseases including asthma and emphysema.However, at the time of the PROP study, there were no objective measures to predict which preterm infants would have persistent respiratory problems after discharge from the hospital. Furthermore, improved survival rates of premature infants and the high prevalence of lasting respiratory morbidities highlight the need for more comprehensive strategies to address both short-term and long-term respiratory complications. Thus, the Prematurity and Respiratory Outcomes Program (PROP) was formed to investigate multiple research hypotheses on the molecular mechanisms that contribute to respiratory disease risk of premature neonates over the first year of life. Specifically, PROP investigators hypothesized that in survivors of extreme prematurity to 36 weeks postmenstrual age (PMA), specific biologic, physiologic and clinical data obtained during the initial hospitalization will predict respiratory morbidity between discharge and 1 year corrected age. Participants: A total of 835 infants were enrolled.Design: PROP was a collaboratively developed multicenter prospective cohort study of very preterm infants from birth through the time of discharge from the NICU and up to one year corrected age.Clinical data included maternal and infant demographics, co-morbidities, and daily infant respiratory, nutritional, and medication data until discharge. These were prospectively collected from birth using medical record review and family interviews. After discharge, phone interviews were conducted with the infant's main caregiver at 3, 6, 9 and 12 months corrected age to assess domains of respiratory morbidity. At 6 and 12 months corrected age, a survey of environmental respiratory irritant exposures and an assessment for gastroesophageal reflux disease were also completed. A standardized physical exam was performed at 36-40 weeks PMA and again at one year corrected age. The exam focused on anthropometrics, vital signs, and respiratory system signs. At 34-41 weeks PMA and within one week of anticipated discharge based on physiologic stability, a set of non-invasive respiratory assessments were performed to assess physiologic biomarkers in infants that were not mechanically ventilated or receiving non-invasive positive pressure ventilation. Respiratory inductance plethysmography (RIP) was performed before and after inhaled albuterol to assess potential airway reactivity. During the RIP study, continuous pulse oximetry was performed during quiet sleep in order to analyze oxygen desaturations and apneas. Standardized oxygen requirement challenge tests were performed at about 36 weeks PMA, and at about 40 weeks PMA if the infant was still hospitalized and was not eligible for, or failed, the previous challenge. Failure was defined as SpO2 20 seconds at any point in the testing. Infants breathing ambient air or that passed the 36 week challenge test underwent a hypoxia challenge consisting of a 15-minute trial of FiO2 of 0.15. Failure was defined as SpO2 The primary outcome was respiratory morbidity, as measured by the presence or absence of substantial post-prematurity respiratory disease (PRD) up to one year corrected age. PRD was classified as a positive response in at least one of four morbidity domains during at least two separate parental interviews. The domains were respiratory medications, hospitalizations for cardiopulmonary cause, respiratory symptoms, and home technology dependence (oxygen, ventilator, or CPAP/BiPAP). Mortality from a respiratory cause was also incorporated.

  Study phs004117

• All you need to know about our new DAC Portal

  With the DAC Portal, it is possible to streamline the process of managing access to sensitive data, ensuring that researchers have the necessary resources to advance scientific discovery while maintaining the highest standards of data protection and privacy. We know that, as a new tool, its first use can be complex. For this reason, in this article we will try to show all the elements of interest. Enjoy! Credentials: who needs to create a new user to access the DAC Portal and who doesn't? Only new users (since September the 12th) need to create an EGA account to access the DAC Portal. The EGA team went one step ahead by creating EGA accounts for former DAC members to login to the DAC Portal. These accounts are linked to the personal email used in the DAC structure: To check the linked email, DAC members can paste the DAC ID right after this link: https://metadata.ega-archive.org/dacs/ (e.g. https://metadata.ega-archive.org/dacs/EGAC00001002543) In case of password oblivion, it is possible to set a new one. All the process is channelled through the personal email. Some DAC members may be interested in updating the DAC email. This action can be done contacting our Helpdesk team. For the correct functioning of the DAC Portal, users must add the missing information of the DAC Profile. For a deeper dive, check out our documentation. The first step: knowing your workspace on the Portal Once logged in to the platform using the EGA User credentials, note the sections available: DACs and Policies. In the first one it is possible to check all user's registered DACs by default. It provides a comprehensive overview of each DAC, including its EGA accessions (EGAC), title, status, and the number of data access requests associated with each DAC. Whereas the Policies section is where users can manage and view all their registered policies, along with their associated EGA accessions, links, and titles. A drop-down menu is available with shortcuts to the most useful pages in the top right corner. It is possible to check DACs and policies, as well as creating new ones. In this menu, users can also contact the Helpdesk team using the “Need Help?” section to make inquiries about DACs and policies. Comprehending the DACs list & making the most of all the features Colours are crucial in the DAC's section as they will indicate the user role and the status in every committee, namely: Yellow: you are the administrator of the DAC and have full control to add other contacts, modify the content, and manage data access requests. Orange: you are a member of the DAC and have the authority to manage data access requests but cannot make any changes to the content. Blue: you have been invited to join the DAC and need to either accept or decline the invitation. Grey: the DAC is currently pending validation by the EGA Helpdesk team. Red: the DAC has been declined by the EGA Helpdesk team. Discover more information on how to view the message from Helpdesk containing the declination reason or how to validate or reject a DAC invitation by taking the tour of the DAC Portal. How to create, register and edit a DAC Creating a DAC is an easy process that only requires users to complete the necessary information. After that, the EGA Helpdesk team will review the proposal and validate the proposal. Once the DAC is validated it is possible for authorised users with admin role to edit it at any time, ensuring that all information and contacts associated with the committee is accurate and up to date. Membership management is controlled by searching for the EGA user looking for their username, email, or organisation. Please, note that for a person's details to appear in this search engine, they must have registered as a EGA user. Data Access Committee administrators manage two types of permissions that apply to contacts: Main contact and Role. Both can be modified at any time: Main contact refers to the primary person we firstly contact for any inquiry about the DAC (please, note that we can contact all DAC members, and this refers to the person we will contact first). Role defines the actions that can be taken by each contact. There are two possible status, admin and member, details of which can be found in the Take the Tour. Keep in mind that, to save the modifications, it is always necessary to click on “Update”. Moreover, it is also possible to delete any contact in a DAC whenever it is needed. The data request process: how to manage access requests The data request process is now channelled through the EGA website. Once a user sends a request access, the petition will go directly to the DAC Portal profile of the DAC members liked to the requested dataset. Whenever a request is received, a sand clock symbol will be displayed next to the DAC responsible for the dataset involved. By clicking on the DAC, it is possible to discover more information about requester(s). In this section, DAC Portal users will also be able to modify the display of the data access requests. It is possible to group requests by dataset accession or username, depending on the user preferences. Additionally, it is possible to isolate specific requests by user or dataset. To accept a request, users must slide the button to the right. Once the button turns green, it signifies that the request is accepted; the requester will be granted access to the requested dataset. To make lives easier, we have implemented a “Select all” button to easily accept or revoke multiple requests at once. To decline requests, it is necessary to slide the button to the left. A red button means the requester will not be granted access to the dataset. The DAC Portal will always ask to submit the reason why the data access was denied. Please, note that any decision, grant or denial, must be confirmed clicking the "Apply" button. This will update the status of the request and notify the requester accordingly. Taking control of the activity in the DAC Portal: checking the requests history The History button is a useful feature that allows users to access a list of all the requests that have been granted. This is especially useful for auditing purposes, as it enables to keep track of who has been granted access to the data and when. To facilitate control for those users with several requests we have included a filtering option. It allows to filter requests by user, mail, dataset, EGA ID, and date (these are combinable to boost the search). Don't forget about policies: creation, management, and update Similarly to the DACs section, in the Policies one users can manage and view all their registered policies. By clicking on any policy, it is possible to view its details as well as making any necessary updates or modifications. The sheets symbol and its adjacent number indicate the quantity of objects using a policy. By clicking in the location symbol users will go directly to the DAC page on the DAC Portal to see more information about that DAC. DAC Portal users can create new policies. The first step requires to link the policy to a registered DAC. After defining the title, users can either add a link to an external URL containing terms & conditions or write the policy content directly on the DAC Portal. Keep in mind that both options can be included. Data Use Ontology (DUO) codes can be added to new policies. These codes are used to specify the permitted and prohibited uses of the data. Please, note that some of them require a modifier to provide additional specificity. Find out more by checking out this specific content on the DAC Portal Tour. Policies can be modified at any given time by clicking on one registered policy, which will display the current information.

  Blog new-dac-portal

• Cellular Diversity of the Developing Human Cerebral Cortex

  We sought to characterize cellular heterogeneity in the human cerebral cortex at a molecular level during cortical neurogenesis. We captured single cells and generated sequencing libraries using the C1TM Single-Cell Auto Prep System (Fluidigm), the SMARTer Ultra Low RNA Kit (Clontech), and the Nextera XT DNA Sample Preparation Kit (Illumina). We performed unbiased clustering of the single cells and further examined transcriptional variation among cell groups interpreted as radial glia. Within this population, the major sources of variation related to cell cycle progression and the stem cell niche from which radial glia were captured. We found that outer subventricular zone radial glia (oRG cells) preferentially express genes related to extracellular matrix formation, migration, and stemness, including TNC, PTPRZ1, FAM107A, HOPX, and LIFR and related this transcriptional state to the position, morphology, and cell behaviors previously used to classify the cell type. Our results suggest that oRG cells maintain the subventricular niche through local production of growth factors, potentiation of growth factor signals by extracellular matrix proteins, and activation of self-renewal pathways, thereby contributing to the developmental and evolutionary expansion of the human neocortex. For study version 2, we have updated this data set to include additional primary cells that we infer to represent microglia, endothelial cells, and immature astrocytes, as well as additional cells from the developing neural retina, and from iPS-cell derived cerebral organoids. The genes distinguishing these cell populations may reveal biological processes supporting the diverse functions of these cell types as well as vulnerabilities of specific cell types in human genetic diseases and in viral infections. For study version 3, we have updated the data set to include additional primary cells, including those published in Nowakowski et al., 2017 (PMID:29217575). For study version 4, we have additionally performed parallel analyses of transcriptomes and physiological responses of 476 single cells isolated from developing human cortex. As a result, we were able to identify physiological response profiles of specific progenitor and neuronal cell types during human cortical development.For study version 5, we have additionally performed bulk RNA sequencing of organotypic primary cultures from the developing human cortex with or without exposure to SARS-CoV-2 to understand the infectability and transcriptomic effects of SARS-CoV-2 on the developing human cortex.For study version 6, we investigated the impact of LIFR signaling on neural proliferation and differentiation of human oRG cells. Specifically, we isolated oRG cells from the primary developing neocortex and cultured them for four weeks with and without LIF treatment. We then performed single-cell RNA sequencing using the Chromium Single Cell 3’ Reagent Kits (v3.1, Dual index) from 10x Genomics to understand the molecular and cellular changes of oRG differentiation upon LIF treatment.

  Study phs000989

• Using Genomics to Reduce Breast Cancer Disparities in the African Diaspora

  Differences in breast cancer incidence and mortality rates between North American Caucasian and African American women are well-described and transcend socioeconomic issues. Black women are diagnosed with breast cancer at a younger median age; have more clinically aggressive disease and stage-for-stage; and have higher mortality rates than age-matched Caucasian women. Black women in West Africa, the origin of the slave trade in the US in the 19th century and thus the founder population for most African Americans, have even higher rates of early-onset, poor-prognosis breast cancer than African American women. Racial difference in the distribution of intrinsic molecular subtypes has been well characterized in the US and throughout the African Diaspora as well. Despite the large efforts on characterizing racial/ethnic differences, however, the reasons women of African ancestry are disproportionately affected by breast cancer incidence and mortality remain poorly understood - largely due to paucity of data on inherent genomic differences that contribute to the disparities in incidence and progression of breast cancer across populations. West Africa Breast Cancer Study (WABCS) is an initiative that aims to comprehensively understand the genetic architecture of breast cancer in West Africans, the founder population of a large proportion of black women in the United States. The objective of the study was to provide a better understanding of the molecular genetic factors that influence prognosis in Nigerian breast cancer patients, and determine which of these alterations may be amenable to available therapy. To that end, we examined the molecular features of breast cancers of indigenous African women using a combination of whole-genome, whole-exome, and transcriptome sequencing (WGS, WES, and RNA-seq) on 194 tumors from Nigerian patients. The goal of this project was to obtain answers to two related research questions using an unscreened population without genetic admixture in Nigeria: 1) why are women of African ancestry more likely to develop aggressive young onset breast cancer? 2) What are the associated genomic and non-genomic risk factors? We hypothesize that the genomic determinants of breast cancer molecular subtypes in women of African ancestry are also molecular drivers of tumor progression and represent targets for interventions to improve clinical outcomes and close the mortality gap. By identifying causal links between genetic variants that promote aggressive tumor progression in Nigerian women in comparison to women from different population found in TCGA and ICGC, the present dataset will have significant public health impact on millions of women in the African Diaspora. The potential to identify novel pathways for interventions to reduce the increasing mortality gap between women of African and European ancestry is huge

  Study phs001687

• Metagenomic Analysis of the Structure and Function of the Human Gut Microbiota in Crohn's Disease

  Inflammatory bowel diseases (IBD), such as Crohn's disease, are chronic, immunologically mediated disorders that have severe medical consequences. The current hypothesis is that these diseases are due to an overly aggressive immune response to a subset of commensal enteric bacteria. Studies to date on IBD have suggested that the disorder may be caused by a combination of bacteria and host susceptibility; however the etiologies of these diseases remain an enigma. In this application, we propose to develop and demonstrate the ability to profile Crohn's disease at an unprecedented molecular level by elucidation of specific biomarkers (bacterial strains, genes, or proteins) that correlate to disease symptoms. To achieve this goal, we will employ a multidisciplinary approach based on metagenomic and metaproteomic molecular tools to elucidate the composition of the commensal microbiota in monozygotic twins that are either healthy or exhibit Crohn's disease (for concordant, both are diseased; for discordant, one is healthy and one is diseased). The central hypotheses of this proposal are (1) that specific members and/or functional activities of the gastrointestinal (GI) microbiota differ in patients with Crohn's disease as compared to healthy individuals, and (2) that it will be possible to elucidate microbial signatures which correlate with the occurrence and progression of this disease by integration of data obtained from 16S rRNA-based molecular fingerprinting, metagenomics, and metaproteomics approaches. To address these hypotheses, three specific aims are proposed: 1) Obtain data on community gene content (metagenome) in a subset of healthy twins and twins with Crohn's Disease to assess potential differences in the metabolic capabilities of the gut microbiota associated with CD, 2) Obtain data on community protein content (metaproteome) in a subset of healthy twins and twins with Crohn's Disease to assess the state of expressed proteins associated with CD, 3) Apply various statistical clustering and classification methods to correlate/associate microbial community composition, gene and protein content with patient metadata, including metabolite profiles and clinical phenotype. The ultimate goal of these efforts is to identify novel biomarkers for non-invasive diagnostics of CD and to eventually identify drug targets (i.e. bacterial strains) for cure or suppression of disease symptoms. PUBLIC HEALTH RELEVANCE: This study aims to unravel the contribution of the bacteria that normally inhabit the human gastrointestinal tract to Crohn's disease by using a multidisciplinary approach to study changes in the structure and function of gut microbial communities in three sets of patient cohorts who have Crohn's disease. These results will be compared with those obtained from the study of healthy individuals and have the potential to identify new biomarkers of disease severity, location, and progression.

  Study phs000257

• Prevention and Early Treatment of Acute Lung Injury Network - Vitamin D to Improve Outcomes by Leveraging Early Treatment (PETAL VIOLET-BioLINCC)

  Data Access NOTE: Please refer to the "Authorized Access" section below regarding accessing data through the BioData Catalyst ecosystem. The data from this accession is not available for download through dbGaP. Biospecimens: Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from PETAL VIOLET include Plasma and Whole Blood. Please note that use of biospecimens in genetic research is subject to a tiered consent. Specimens may not be used to produce commercial products.Objectives: To evaluate the effect of short-term vitamin D supplementation on mortality among critically ill patients with a vitamin D deficiency.Background: Observational data indicate that vitamin D deficiency is common among critically ill patients and constitutes a potentially modifiable risk factor associated with longer lengths of stay in the hospital and intensive care unit (ICU), lung and other organ injury, prolonged mechanical ventilation, and death. In a previous phase 2 trial, vitamin D supplementation administered to vitamin D-deficient, critically ill patients was associated with lower observed mortality than placebo at 28 days and at 6 months. Because of the need for a larger, phase 3 trial, the PETAL-VIOLET study was initiated to determine if early administration of high-dose vitamin D3 would reduce all-cause mortality among critically ill patients with a vitamin D deficiency.Participants: 1360 patients underwent randomization, 690 were assigned to the vitamin D group and 668 were assigned to the placebo group. Of the 1078 patients confirmed to have a vitamin D deficiency by liquid chromatography-tandem mass spectrometry (LC-MS-MS), 538 had been assigned to the vitamin D group and 540 had been assigned to the placebo group.Design: PETAL-VIOLET was a multicenter, double-blind, placebo-controlled, phase 3 trial. Patients were enrolled within 12 hours after the clinician's decision to admit the patient to the ICU from the emergency department, hospital ward, operating room, or outside facility. Patients were tested for vitamin D deficiency, with a threshold of plasma 25-hydroxyvitamin D level of less than 20 ng per milliliter. Patients were randomly assigned in a 1:1 ratio, stratified according to site, to receive either a single enteral (administered orally or through a nasogastric or orogastric tube) dose of 540,000 IU of vitamin D3 or matched placebo, in liquid form, administered within 2 hours after randomization.Conclusions: After the first interim analysis, the data and safety monitoring board recommended that the trial be stopped for futility.A single 540,000 IU enteral dose of vitamin D3 administered early during critical illness rapidly corrected vitamin D deficiency but did not provide an advantage over placebo with respect to mortality or other clinically important end points.

  Study phs003879

• PanCuRx Translational Research Initiative

  The goal of the PanCuRx TRI is to seek solutions to the high fatality rate of pancreatic adenocarcinoma (PDAC), the most common type of pancreatic cancer, by generating new knowledge about the genetics and biology of the disease, mechanisms of how tumours grow and tailored treatment options. PDAC is the fourth leading cause of cancer death in Canada and is expected to become the second-leading cause of cancer death within the next decade. The current five-year survival rate of eight per cent is the lowest of all epithelial cancers. There are major clinical challenges to treating the disease, including the fact that PDAC spreads to other parts of the body early so surgical removal of the tumour benefits few patients, that PDAC has proven relatively resistant to systemic therapies such as chemotherapy and that there has been limited benefit from the use of newer molecular targeted agents. The PanCuRx team has created the world’s first resource of tumour-purified PDAC whole genomes; more than 500 PDAC samples, with combined clinical annotation, have been successfully sequenced and analyzed at the Ontario Institute for Cancer research in Toronto. The resulting clinical genomic resource created from this data has led to multiple new findings that have established a framework to better understand PDAC biology and lays the foundation for new genomic approaches to better understanding the disease. The team also launched a clinical trial called COMPASS (Comprehensive Molecular Characterization of Advanced Ductal Pancreas Adenocarcinoma for Better Treatment Selection: A Prospective Study), which is recruiting patients with advanced PDAC (both locally advanced and metastatic) at The Princess Margaret Cancer Centre (PM) in Toronto. The study uses the molecular results from individual patient tumours to guide selection of better second line treatment on a case-by-case basis. The primary objective of the initial study was to assess the feasibility of collecting tumour materials from patients with advanced PDAC and delivering results within 56 days of biopsy. Having achieved this objective, the trial has expanded to other cancer centres across Canada. Pancreatic cancer is one of the most deadly forms of cancer and outcomes have not improved in four decades. The PanCuRx initiative is providing a better understanding of the disease and actively applying new knowledge to cancer patients through clinical trials. This knowledge will help to improve quality of life and prolong survival for pancreatic cancer patients worldwide.

  Study EGAS00001002543

• sn-RNAseq profiling of the impact of a cytokine storm model in human cardiac organoids

  We developed conditions to model conditions of diastolic dysfunction caused by inflammatory factors in human cardiac organoids. Our organoid model is based on conditions promoting maturation (Mills et al., PNAS, 2017 and Voges et al., In Revision) and incorporating human pluripotent stem cell derived cardiomyocytes, epicardial cells, fibroblasts, endothelial cells and pericytes. Following 15 days of differentiation (Voges et al., Development, 2017) we formed human cardiac organoids incorporating both our multicellular differentiation (Mills et al., PNAS, 2017) and additional endothelial cells (Voges et al., In Revision). After another 12 days of maturation in 5 days maturation medium and 5 days weaning medium (Voges et al., In Revision) human cardiac organoids were either treated with weaning medium or “cardiac cytokine storm” comprised of 100 ng/ml IFNg, 10 ng/ml IL-1 β and 10 µg/ml poly(I:C). After 48 hours human cardiac organoids were harvested and snap frozen in -80C before nuclei isolation and single nuclei RNA sequencing.Pooled hCO (~40) were homogenized in 4 mL lysis buffer (300 mM sucrose, 10 mM Tris-HCl (pH = 8), 5 mM CaCl2, 5 mM magnesium acetate, 2 mM EDTA, 0.5 mM EGTA, 1 mM DTT)(all Sigma-Aldrich) with 30 strokes of a dounce tissue grinder (Wheaton). Large pieces of hCO were allowed to settle and homogenate was passed through pre-wetted 40 µm cell strainers (Becton Dickinson). Remaining hCO material in the douncer was resuspended in 4 mL and the douncing and filtering steps were repeated twice. All steps of the homogenization were performed on ice. The filtered homogenate was centrifuged at 1500 x g for 5 min at 4oC. Nuclei pellets were then re-suspended in PBS. A fraction of resuspended nuclei were then stained with hoechst nuclear stain (1:500 dilution) and counted on a haemocytometer under fluorescent microscope.The nuclei were then re-centrifuged (1500 x g for 5 min at 4°C) and resuspended at a density to load ~5,000 nuclei per sample. Cell were loaded into the Chromium Controller (10X Genomics) for gel bead emulsion (GEM) formation. Library preparation was conducted according to the manufacturer’s recommended protocol using the Chromium Next GEM Single Cell 3’ GEM, Library & Gel Bead Kit v3.1. Libraries were sequenced on the NextSeq 500/550 v2 (Illumina) with 150 bp reads.In the snRNA-seq we note the lower than expected percentage of non-myocytes and the loss of endothelial cells (Mills et al., PNAS, 2017 and Voges et al., In Revision), indicating the protocol requires further optimization for hCO samples.

  Study EGAS00001005174

• Beyond BRCA deficiency: Clinical and molecular predictors of survival in patients with BRCA-deficient tubo-ovarian high-grade serous carcinoma

  Homologous recombination DNA repair deficient (HRD) tumors account for about 50% of tubo-ovarian high-grade serous carcinomas (HGSC) and are associated with a high response to platinum-based chemotherapy. However, a subset of patients with HRD tumors have unexpected resistance to chemotherapy and experience short survival. Our study compared BRCA-deficient and proficient HGSC among patients with short (<3 years, the lowest quartile of overall survival (OS)) versus longer-term (>3 year OS) to identify prognostic markers and potential therapeutic opportunities. Primary tumors from a cohort of patients with advanced-stage HGSC (n=154) enriched for those with HRD tumors and short survival (n=42) were analyzed using whole-genome sequencing, bulk RNA-sequencing, and DNA methylation profiling. A subset of HRD tumors (n=143) were characterized for immune cell densities by multiplex immunofluorescence. Clinicopathological features were assessed in 1,389 patients with HGSC, including 282 with pathogenic germline BRCA variants (gBRCApv). Findings were validated in two international HGSC cohorts: the Ovarian Tumor Tissue Analysis consortium (n=5,875) and Multisciplinary Ovarian Cancer Outcome Group (n=895). In gBRCApv-carriers, residual disease following surgical cytoreduction was not associated with shorter OS unlike in non-carriers where it was strongly associated. While most patients with gBRCApv had a more favorable OS compared to non-carriers, a survival advantage was not apparent in those with variants located outside of BRCA1 exon 10/23 and BRCA2 exon 11/27. Patient survival correlated with HRD score, such that those with a score ≥63 had significantly longer OS compared to those with HRD scores of 42-63 and <42. While higher HRD scores were associated with better survival outcomes, most gBRCApv carriers with a short survival had tumor HRD scores that exceeded the threshold typically considered predictive of a good response to carboplatin or PARP inhibitors. BRCA2-deficient HGSC with loss of the tumor suppressor NF1 was associated with exceptionally favorable outcome (median OS 17 years), whereas amplification of both PIK3CA and RAD21, was associated with poor outcome in BRCA2-deficient HGSC (median OS 2.9 years). The density of tumor-infiltrating CD8+ PD-1+ T cells was prognostic for OS in gBRCApv-carriers. In summary, rather than simply the presence or absence of a germline BRCA pathological variant influencing patient survival, the co-occurrence of specific somatic gene alterations, the extent of immune cell infiltration, the level of homologous recombination deficiency, and BRCA-variant location may modify clinical outcomes in patients with BRCA-deficient HGSC. Analysis of exceptional outcome patients, in this case gBRCApv-carriers with an atypically short survival, may identify determinants of outcome applicable to the wider HGSC patient population.

  Study EGAS00001008059

• Detection of Colorectal Cancer Susceptibility Loci Using Genome-Wide Sequencing

  The Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) is a collaborative effort comprised of a coordinating center and scientific researchers from well-characterized cohort and case-control studies. This international consortium aims to accelerate the discovery of common and rare genetic risk variants for colorectal cancer by conducting large-scale meta-analyses of existing and newly generated genome-wide association study (GWAS) data, whole genome sequencing, replicating and fine-mapping of genetic discoveries, and investigating how genetic risk variants are modified by environmental risk factors. To expand these efforts, we assembled case-control sets or nested case-control sets from 6 different North American or European studies. Summary descriptions and study participant inclusions/exclusion criteria for each of these studies are detailed below. Cancer Prevention Study II (CPS II): The CPS II Nutrition cohort is a prospective study of cancer incidence and mortality in the United States, established in 1992 and described in detail elsewhere (Calle et al., 2002 PMID:12015775; Campbell et al., 2014 PMID:25472679). At enrollment, participants completed a mailed self-administered questionnaire including information on demographic, medical, diet, and lifestyle factors. Follow-up questionnaires to update exposure information and to ascertain newly diagnosed cancers were sent biennially starting in 1997. Reported cancers were verified through medical records, state cancer registry linkage, or death certificates. The Emory University Institutional Review Board approves all aspects of the CPS II Nutrition Cohort. We restricted to samples that had blood DNA source. Controls were matched to cases in a case/control ratio of 2:1 on reference year and sex. Darmkrebs: Chancen der Verhütung durch Screening (DACHS): This German study was initiated as a large population-based case-control study in 2003 in the Rhine-Neckar-Odenwald region (southwest region of Germany) to assess the potential of endoscopic screening for reduction of colorectal cancer risk and to investigate etiologic determinants of disease, particularly lifestyle/environmental factors and genetic factors. Cases with a first diagnosis of invasive colorectal cancer (International Classification of Diseases 10 codes C18-C20) who were at least 30 years of age (no upper age limit), German speaking, a resident in the study region, and mentally and physically able to participate in a one-hour interview, were recruited by their treating physicians either in the hospital a few days after surgery, or by mail after discharge from the hospital. Cases were confirmed based on histologic reports and hospital discharge letters following diagnosis of colorectal cancer. All hospitals treating colorectal cancer patients in the study region participated. Based on estimates from population-based cancer registries, more than 50% of all potentially eligible patients with incident colorectal cancer in the study region were included. Community-based controls were randomly selected from population registries, employing frequency matching with respect to age (5-year groups), sex, and county of residence. Controls with a history of colorectal cancer were excluded. Controls were contacted by mail and follow-up calls. The participation rate was 51%. During an in-person interview, data were collected on demographics, medical history, family history of CRC, and various life-style factors, as were blood and mouthwash samples. Routine formalin-fixed, paraffin-embedded (FFPE) tumor samples from the patients enrolled were requested from the pathology institutes and used for tumor tissue analyses. This analysis includes participants with blood source DNA that were recruited up to 2010 in this ongoing study. Controls were matched to cases on reference age and sex in a case/control ratio of 2:1. Health Professionals Follow-up Study (HPFS): A parallel prospective study to the NHS (Nurses' Health Study). The HPFS cohort comprised 51,529 men aged 40-75 who, in 1986, responded to a mailed questionnaire (Rimm et al., 1990 PMID:2090285). Participants provided information on health related exposures, including current and past smoking history, age, weight, height, diet, physical activity, aspirin use, and family history of colorectal cancer. Colorectal cancer and other outcomes were reported by participants or next-of-kin and were followed up through review of the medical and pathology record by physicians. Overall, more than 97% of self-reported colorectal cancers were confirmed by medical record review. Information was abstracted on histology and primary location. Incident cases were defined as those occurring after the subject provided the blood sample. Prevalent cases were defined as those occurring after enrollment in the study but before the subject provided the blood sample. Follow-up evaluation has been excellent, with 94% of the men responding to date. Colorectal cancer cases were ascertained through January 1, 2008. In 1993-1995, 18,825 men in the HPFS mailed blood samples by overnight courier, which were aliquoted into buffy coat and stored in liquid nitrogen. In 2001-2004, 13,956 men in the HPFS who had not provided a blood sample previously mailed in a swish-and-spit sample of buccal cells. Incident cases were defined as those occurring after the subject provided a blood or buccal sample. Prevalent cases were defined as those occurring after enrollment in the study in 1986, but before the subject provided either a blood or buccal sample. Participants with histories of cancer (except nonmelanoma skin cancer), ulcerative colitis, or familial polyposis, case-control sets were excluded. Control participants were required to be free of invasive colorectal cancer and non-invasive (stage 0 in situ) colorectal cancer. For this study, only European ancestry participants with blood source DNA and incident colorectal cancer cases were eligible for selection. Since enrollment year and sex matched exactly, controls were randomly selected in a case/control ratio of 2:1. Nurses Health Study (NHS): The NHS cohort began in 1976 when 121,700 married female registered nurses age 30-55 years returned the initial questionnaire that ascertained a variety of important health-related exposures (Belanger et al., 1978 PMID:248266). Since 1976, follow-up questionnaires have been mailed every 2 years. Colorectal cancer and other outcomes were reported by participants or next-of-kin and followed up through review of the medical and pathology record by physicians. Overall, more than 97% of self-reported colorectal cancers were confirmed by medical-record review. Information was abstracted on histology and primary location. The rate of follow-up evaluation has been high: as a proportion of the total possible follow-up time, follow-up evaluation has been more than 92%. Colorectal cancer cases were ascertained through June 1, 2008. In 1989-1990, 32,826 women in NHS I mailed blood samples by overnight courier, which were aliquoted into buffy coat and stored in liquid nitrogen. In 2001-2004, 29,684 women in NHS I who did not previously provide a blood sample mailed a swish-and-spit sample of buccal cells. Incident cases were defined as those occurring after the subject provided a blood or buccal sample. Prevalent cases were defined as those occurring after enrollment in the study in 1976 but before the subject provided either a blood or buccal sample. Participants with histories of cancer (except nonmelanoma skin cancer), ulcerative colitis, or familial polyposis, case-control sets were excluded. For this study, only European ancestry participants with blood source DNA and incident colorectal cancer cases were eligible for selection. Since enrollment year and sex matched exactly, controls were randomly selected in a case/control ratio of 2:1. Prostate, Lung, Colorectal and Ovarian Cancer Screening Trail (PLCO): PLCO enrolled 154,934 participants (men and women, aged between 55 and 74 years) at ten centers into a large, randomized, two-arm trial to determine the effectiveness of screening to reduce cancer mortality. Sequential blood samples were collected from participants assigned to the screening arm. Participation was 93% at the baseline blood draw. White colorectal cancer cases with a family history of colorectal cancer (no history of ulcerative colitis, Crohn's Disease, diverticulitis, Gardner's syndrome, Familial Polyposis) and successful genotyping from previous Peters GWAS were selected for this project. Controls were matched to cases on reference age and sex in a case/control ratio of 2:1. Women's Health Initiative (WHI): WHI is a long-term national health study that has focused on strategies for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women. The original WHI study included 161,808 postmenopausal women enrolled between 1993 and 1998. The Fred Hutchinson Cancer Research Center in Seattle, WA serves as the WHI Clinical Coordinating Center for data collection, management, and analysis of the WHI. The WHI has two major parts: a partial factorial randomized Clinical Trial (CT) and an Observational Study (OS); both were conducted at 40 Clinical Centers nationwide. The CT enrolled 68,132 postmenopausal women between the ages of 50-79 into trials testing three prevention strategies. If eligible, women could choose to enroll in one, two, or all three of the trial components. The components are: Hormone Therapy Trials (HT): This double-blind component examined the effects of combined hormones or estrogen alone on the prevention of coronary heart disease and osteoporotic fractures, and associated risk for breast cancer. Women participating in this component with an intact uterus were randomized to estrogen plus progestin (conjugated equine estrogens [CEE], 0.625 mg/d plus medroxyprogesterone acetate [MPA] 2.5 mg/d) or a matching placebo. Women with prior hysterectomy were randomized to CEE or placebo. Both trials were stopped early, in July 2002 and March 2004, respectively, based on adverse effects. All HT participants continued to be followed without intervention until close-out. Dietary Modification Trial (DM): The Dietary Modification component evaluated the effect of a low-fat and high fruit, vegetable and grain diet on the prevention of breast and colorectal cancers and coronary heart disease. Study participants were randomized to either their usual eating pattern or a low-fat dietary pattern. Calcium/Vitamin D Trial (CaD): This double-blind component began 1 to 2 years after a woman joined one or both of the other clinical trial components. It evaluated the effect of calcium and vitamin D supplementation on the prevention of osteoporotic fractures and colorectal cancer. Women in this component were randomized to calcium (1000 mg/d) and vitamin D (400 IU/d) supplements or a matching placebo. The Observational Study (OS) examines the relationship between lifestyle, environmental, medical and molecular risk factors and specific measures of health or disease outcomes. This component involves tracking the medical history and health habits of 93,676 women not participating in the CT. Recruitment for the observational study was completed in 1998 and participants were followed annually for 8 to 12 years. All centrally confirmed White cases of invasive colorectal cancer, or death from colorectal cancer were selected as potential cases from the March, 2011 database. Case priory lists are: 1) have positive family history of colorectal cancer; 2) randomly select cases until we get a total of n=800 cases. Control participants were required to be White, free of invasive colorectal cancer and non-invasive (stage 0 in situ) colorectal cancer. Centrally denied cases of colorectal cancer were not allowed into the control pool. Case and control participants were subject to the following exclusion criteria: (1) had prior history of colorectal cancer at baseline; (2) had no available DNA (DNA searching as Nov 15, 2012); (3) cannot be deposited to dbGaP; (4) lost to follow-up after enrollment; (5) selected for WHI study M26 Phase II. Controls were matched to cases in a case/control ratio of 2:1. In order to get 2 cases with 1 control, cases were grouped by enrollment year (a total of 5 groups). For each year group, around 50% cases were selected to match controls. In total, 401 cases were selected to match controls. Matching was done on enrollment year, which was matched exactly. For additional information, see dbGaP: phs000200 and ClinicalTrials: NCT00000611.

  Study phs001554

• AmsterdamUMC Data Access Committee for the study "Multi-omic analysis of thyroid dysfunction in Down Syndrome"

  The current data access committee reviews and assesses data requests of researchers that seek to gain access to data acquired as part of the "Multi-omic analysis of thyroid dysfunction in Down Syndrome" study as performed at the AmsterdamUMC, Amsterdam, Netherlands.

  Dac EGAC50000000186

• Patient-derived xenograft models of head and neck cancers

  Establishment and characterization of two patient-derived xenograft models from HNSCC patients , initiatlly treatment-naive, and for which cetuximab-acquired resistant model couterparts have been generated. All models have been characterized at genomic level. HNSCC tissues were obtained from surgical resections at Cliniques universitaires St Luc in Brussels (Belgium).

  Dac EGAC50000000502

• MethylBERT enables read-level DNA methylation pattern identification and tumour deconvolution using a Transformer-based model

  This is the DAC for the study "MethylBERT enables read-level DNA methylation pattern identification and tumour deconvolution using a Transformer-based model" of Pavlo Lutsik (DKFZ B370/KU Leuven, pavlo.lutsik@kuleuven.be) and Clarissa Gerhauser (DKFZ B370, c.gernauser@dkfz.de)

  Dac EGAC50000000497

• Dac for "ARHGAP11A Maintains Cortical Progenitor Identity Through RHOA–ROCK Signalling During Human Brain Development" with Julia.ladewig@zi-mannheim.de, Department of Translational Brain Research. Moritz Mall, m.mall@dkfz-heidelberg.de, German Cancer Research Center (DKFZ). Yannick Hass, yannick.hass@zi-mannheim.de, Department of Translational Brain Research. Anne Hoffrichter, anne.hoffrichter@zi-mannheim.de, Department of Translational Brain Research, Central Institute of Mental Health

  Dac EGAC00001003603

• Single-cell RNA-sequencing for peripheral blood mononuclear cells from COVID-19 patients and healthy controls of Japanese

  We performed single-cell RNA-sequencing of peripheral blood mononuclear cells obtained from COVID-19 patients and healthy controls.

  Study JGAS000593

• Single-cell RNA-sequencing for peripheral blood mononuclear cells from COVID-19 patients and healthy controls of Japanese

  We performed single-cell RNA-sequencing of peripheral blood mononuclear cells obtained from COVID-19 patients and healthy controls.

  Study JGAS000543

• WGS of 11 MPNSTs, 7 ANNUBPs and 7 blood and normal tissue controls

  Whole-genome sequencing (WGS) of 11 MPNSTs, 7 ANNUBPs and 7 controls (6 blood and 1 normal tissue) sequenced for Magallon-Lorenz, 2026. Sequenced at BGI with DNBseq technology (2x150bp) following standard protocols. Raw fastq files provided.

  Dataset EGAD50000002492

• cfDNA sWGS BAM — Metastatic colorectal cancer

  Plasma cirDNA sWGS for metastatic colorectal adenocarcinoma at diagnosis prior to systemic therapy. Libraries DSP/SSP (per sample). Sequencing by IntegraGen (2022–2024). Alignment: GRCh38 with BWA-MEM; BAMs sorted/indexed; delivered as primary mapped reads only (filters/MAPQ in analysis metadata). Controlled access

  Dataset EGAD50000001879

• HOVON152 Trial shallow Whole Genome Sequencing

  Associated with Molecular profiling of HGBCL-DH-BCL2 patients treated in the HOVON-152 triaL. Targeted sequencing of 30 samples from 30 High-grade B-cell lymphoma patients. Targeted sequencing was used for identify genomic alterations associated with patient outcome.

  Dataset EGAD50000002094