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• Effect_of_FAM50_knockout_on_the_transcriptome

  A knockout clone has been generated for both FAM50A and FAM50B; knockout of the other gene is then performed and the transcriptome is analysed to look at the effect of dual gene loss.

  Study EGAS00001004836

• Efficacy and safety of entrectinib in patients with ROS1-positive advanced/metastatic non-small cell lung cancer (NSCLC) from the Blood First Assay Screening Trial (BFAST)

  BFAST is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations, identified by blood-based molecular testing. We present data from Cohort D (ROS1-positive). Patients ≥18 years old with stage IIIB/IV, ROS1-positive NSCLC detected by blood-based testing, received entrectinib 600 mg daily. At data cut-off (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint; the confirmed objective response rate (ORR) by investigator was 81.5% which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR: 73.4%, data cut-off May 2019, ≥12 months follow-up). The safety profile of entrectinib was consistent with prior reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing and support the clinical value of blood-based testing to inform clinical decision-making.

  Study EGAS50000000105

• Genomic Characterization CS-MATCH-0007 Arm B

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing, RNA sequencing and if possible, whole-genome, methylation and miRNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH clinical trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm B is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with HER2- activating mutations are treated with Afatinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002028

• Genomic Characterization CS-MATCH-0007 Arm Z1B

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm Z1B is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with CCND1, CCND2, and/or CCND3 amplifications are treated with Palbociclib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002180

• WGBS data of solid liver tumor DNA, and WGBS data of cell-free DNA derived from human blood, for CancerDetector study

  The blood samples of four liver cancer patients and four healthy people, and the solid liver tumor samples of two liver cancer patients are collected for this dataset. Blood samples were centrifuged first at 1,600 × g for 10 minutes, and then the plasma was transferred into new micro tubes and centrifuged at 16,000 × g for another 10 minutes. The plasma was collected and stored at -80⁰C. CfDNA was extracted from 5 ml plasma using the Qiagen QIAamp Circulating Nucleic Acids Kit and quantified by Qubit 3.0 Fluoromter (Thermo Fisher Scientific). Bisulfite conversion of cfDNA was performed by using EZ-DNA-Methylation-GOLD kit (Zymo Research). After that, Accel-NGS Methy-Seq DNA library kit (Swift Bioscience) was used to prepare the sequencing libraries. The DNA libraries were then sequenced with 150bp paired-end reads.

  Dataset EGAD00001004317

• DAC Portal documentation

  DAC Portal Welcome to the DAC Portal documentation! If you are involved in governance or legal aspects, technical or operational aspects, or serving as a data steward, this page will be helpful for you. By exploring these materials, you can define your own Data Access Committee (DAC) and policies, understand the minimal requirements for a DAC and a policy object, and comprehend how the EGA data access requests are managed. DAC Portal Index Setting up your account DACs and Policies Pending Request table Manage Data Requests History page Audit your DACs, policies, and datasets Deprecation User Preferences DAC API - A programmatic approach Setting up your account Register yourself as an EGA user. The Helpdesk team will validate your account (this could take up to 48 hours). After validation, you will receive an email with a link to verify your email - Make sure you click on the link to verify your account! If you don’t receive the email, please check your spam folder. Once your account is active you can login to the DAC Portal. We recommend you to check out the Take The Tour! DACs and Policies Create a DAC Click on Create a DAC Add the title and description to your DAC. Once ready, click on the ‘Create’ button. You will have to wait until the Helpdesk Team validates the creation of your DAC. Once approved by Helpdesk, your DAC will be assigned with a persistent identifier (EGAC). Edit a DAC Once your DAC is registered and approved, you can edit it and add contacts. Remember, you can add as many contacts as needed. And, you can also remove/add contacts anytime. To add a contact, you must write the username or email of a registered EGA user in the Members field. Once you have typed the whole username or email, a drop-down menu will appear where you can select the contact. Select a contact from the drop-down menu. Make sure you write the full username or email of the contact so it appears as an option. Make sure that you select one main contact. Set up the role you want to grant to the new contact of the DAC. We recommend you to check out the FAQ to learn more about the different roles! After adding all the necessary contacts and assigning roles, click on Update. This will send an email notification to the new DAC member, letting them know about the invitation to managing the DAC. Once they log into the DAC Portal, they will be able to either accept or turn down the invitation. Create a policy First, please note that all information registered in a policy metadata object will be publicly available on the EGA website. For each released dataset, all users will be able to read the policy under the “Data Access” tab. Select Create a Policy from the Policies tab. Select the DAC that you want your policy to depend on. Add the title and terms and conditions for accessing and using your data. If you already have an external website for data access requests, you can add the URL directly here (see example here). You can find a template of a Data Access Agreement (DAA) document in our Policy documentation page. The DAA template is provided for guidance only and should be adapted to suit your own purpose depending on the security policies, terms for publication or embargoes, and restrictions on data use or sharing. You can also add Data Use Ontologies (DUO) to your policy. These DUO codes are used to semantically tag the terms and conditions of using the data linked to the policy (example). For more information, you can refer to the Data Uso Ontology documentation. Once completed, make sure to click the Create button in order to register your policy. A persistent identifier (EGAP) will be assigned automatically. Edit a policy Please, note that you will not be able to edit the policy if it shows in orange. Meaning that you are a member of the DAC linked to that policy. Members don’t have edit rights. Only admins can edit objects. You can check your registered policies on My policies, available at the menu in the top-right corner. Select your policy. It will then display the information of that policy, allowing you to edit the information. Once you are done with the modifications, click Update. Pending Requests Table Table Settings Upon selecting a specific DAC, you will be presented with a customisable table showcasing all pending data access requests. This table allows you to tailor the displayed information according to your preferences by selecting desired columns. Available Columns (Displayed with the Eye Icon): Date: The date when the data access request was submitted. Full Name: Name and surname of the user submitting the request. Email: Email address associated with the user's request. Username: The username linked to the EGA account of the user submitting the request. Organisation: Affiliated organisation of the user submitting the request. Dataset: EGA accession ID for the requested EGA dataset. Dataset Title: Title of the requested dataset. DAC Comment: Space provided for internal comments related to the request. Expiration: Option to specify an expiration date for granted permissions. Check more information on the pending request table here! Table Filters By default, all data access requests are displayed. However, you have the option to apply filters to refine your view. Follow these steps to apply filters: Click on the More button. This action will reveal the different columns available for applying filters. As you select columns, the checked fields will be displayed at the top of the request table. Choose the specific values within the selected columns that you want to filter for. Click the Search button to apply the selected filters. Do you find yourself frequently applying the same filters? You can save multiple combinations of filters for easy access at any time! Here's how: Click the Save button. Provide a descriptive name for the filter combination. Click Save to confirm. To load saved filters, simply select the saved filter from the dropdown menu to apply it automatically. Check more information on filters here! Advanced Search For users requiring more granular control over their data access requests, the DAC Portal offers an Advanced Search feature using JIRA Query Language (JQL). With JQL, you can craft precise and complex queries to filter and retrieve specific data access requests based on various criteria such as date, user details, dataset attributes, and more. Using JQL's flexibility, you can create custom queries to meet your specific needs, allowing for advanced filtering options beyond the standard filters provided. You can find the Advanced Search feature following these steps: Click the … button Select Advanced To view the allowed fields for filtering and explore all available options, simply click on the info icon. Once you have written the filtering values, click the Search button to apply. Check more information on filters here! Manage Data Requests Upon logging into the DAC Portal, you'll notice a sand clock icon next to the DAC ID, indicating the number of pending requests. Click on the DAC to review these requests. Accept requests Click on the right side of the toggle button to grant access to the user. You can manage other requests before proceeding to the next step. After managing the requests, click on the Apply button. A confirmation box will appear summarising the options to be applied. Click on Yes, Confirm to proceed with granting permissions. Deny requests Click on the left side of the toggle button to deny access to the user. Provide a reason for the denial. Note that the user will receive an email with this reason. Click on the Done button. You can manage other requests before proceeding to the next step. After managing the requests, click on the Apply button. A confirmation box will appear summarising the options to be applied. Click on Yes, Confirm to proceed with denying permissions. Tips! Apply a filter to view all requests to be managed at once. Use the toggle in the row with column names to grant or deny permissions for multiple requests simultaneously. You can grant and deny permissions in the same action, simplifying the process. The confirmation box will provide a summary of all actions, including grants, denials, DAC comments, and expiration dates. History Page The History page serves as a dedicated space to view information regarding all requests managed by all DAC members. Here, you can review active permissions and revoke them as needed. Go to the History page by clicking on the "HISTORY" button from a DAC page in the DAC Portal. Here are the different row types you may find: Current permissions: row in green with a toggle button to revoke permissions on the right. Approved requests: row in green, with no toggle button. Request denied: row in red with “request denied” on the right. Permission revoked: row in red with “permission revoked” on the right. Distinctions to Note! Between Request Denied and Permission Revoked: Request Denied: Refers to requests that were rejected from the outset, indicating that access to the dataset was never granted. Permission Revoked: Indicates that permissions were previously granted but have since been revoked. Users with permissions revoked have previously accessed the dataset. Between Approved Request and Current Permissions: Approved Request: Represents an entry when a data access request has been approved in the past. Current Permissions: Denotes ongoing permissions where a user has present access to the dataset. An approved request may now appear as Permission Revoked in the present. By observing these different rows, users can gain insight into the complete history of a user's interactions and permissions regarding a dataset over time. To revoke access to a specific user for a dataset, follow these steps: Go to History page Look for the row with the specific permissions. You can use the filters! Click on the toggle button to revoke access. Add a denial reason. Bear in mind that the requester will receive the denial reason! Click on the Apply button. Check more information on the Hisotry page here! Audit your metadata objects In the DAC Portal, you can efficiently manage and audit various metadata objects pertinent to your role as a Data Controller. Upon accessing the DAC Portal, you will encounter three primary tabs on the homepage: DAC: Contains information about Data Access Committees (DACs). Policies: Provides insights into linked policies. Datasets: Displays datasets and relevant details. Within each tab, you'll find a comprehensive list of the objects you manage, these being grouped by type (DAC, Policies, Datasets), as well as by your role (member/admin). Whilst the lists give you a quick look, to check how things are connected, we've added a table at the bottom DACs and policies. DACs Let’s check which policies are linked to a specific DAC: Go to "My DACs." Select a DAC. Click on "EDIT" to see more details. You are now on this page: Scroll down to see the linked policies. Click on “List of linked policies of this DAC” and you will see a list of all policies linked to your selected DAC. Policies Do you want to view a list of datasets connected to a particular policy? Follow the same steps mentioned earlier, but head to the policy tab this time. In the policy tab, you'll find a list of all your policies. Here, you may notice two different icons next to the policy ID (EGAP): DAC Icon (): This represents the DAC. Hover your mouse over the icon to see the DAC ID. Dataset icon (): This indicates datasets falling under that policy. The number next to the icon tells you how many datasets are linked to the policy. For example, if you see "2" next to the icon, it means there are two datasets linked to that policy. If you want to check the linked datasets and their relevant information, simply click on a specific policy. You'll then find the "List of linked datasets of this policy" at the bottom of the page. Datasets Finally, in the dataset tab, by default you will see a list of all the datasets you can manage with all your DACs and policies. Yet, we've included two handy ways to organise them: DAC vs. policy: You can group by datasets, either by DAC or policy. Released vs. unreleased: You can sort out datasets based on their release status. Feel free to experiment with both options! For instance, if you want to see which DACs have unreleased datasets, simply select DAC and unreleased, and you'll get the details you need! Deprecation Do you have a bunch of metadata objects like DACs and policies that you don’t need anymore? This section shows you how to get rid of them! But what does "deprecation" mean for EGA? It's basically changing the status of a metadata object to "deprecated," which means we won't be using it in the future. In simple terms, it's like saying these objects are no longer useful. However, because we believe in making metadata FAIR, once an object has a persistent identifier, we can't just delete it. So, instead of deleting, we deprecate it. Here's a helpful tip! If you want to make a metadata object disappear from the DAC Portal, deprecate it. You won’t see it in the portal anymore! Let’s say you want to deprecate a DAC. Let’s do it! Go to "My DACs." Select a DAC. Click "EDIT" to see more details. You are now in this page: Click on the Deprecate button It will then appear a message. There are two options here: Your DAC is not linked to any policy, hence it’s ready to be deprecated. Click on “Yes. Confirm” to deprecate your DAC object! Your DAC is linked to at least one policy, and you need to either: Deprecate the linked policy first, or Link the policy to a different DAC Now, let’s say you don’t want to get rid of the policy altogether, but you want to change the DAC it’s linked to. Here's how: Go to the policy tab. Find the policy you want to change (for example, EGAP50000000019). Choose a new DAC to link it to. Click on Update. See the Edit Policy section for more details. After ensuring that the DAC we want to deprecate isn’t linked to any policy, return to the "My DACs" section and follow the steps outlined previously. This will lead you to a confirmation message. You can only deprecate DACs and Policies. To deprecate a dataset, please contact our Helpdesk team. Check more information on how deprecation works here! User Preferences We have implemented email notifications in the DAC Portal. Here’s the complete list: DACs: Pending requests Approved by Helpdesk Rejected by Helpdesk DAC Invitation Requesters: Data access request approved Data access request denied Permissions revoked Upcoming expiration date As a DAC member, you will be able to decide whether you want to receive the DAC notifications or not. For that, go to the top-right corner menu, select User Preference. You will be able to decide whether you want to receive notifications for: Approved by Helpdesk Rejected by Helpdesk DAC Invitation For pending requests, you will be able to select how often do you want to receive the notification: Daily Weekly Fortnightly As a DAC member, you are responsible for managing data access requests. Consequently, you will receive notifications for pending requests. If you prefer not to manage these requests, please arrange to be removed as a contact for your DAC. Here's a tip! Do you have a pending request that you don’t want to receive a notification? Add a DAC comment! The EGA understands that a request resolution can take some time, for this reason, if you add a comment (make sure you save it by clicking the APPLY button!) we will filter those requests at the time of sending the notification! DAC API - A programmatic approach In addition to the new DAC Portal, we are excited to announce the release of the DAC API. This enables users to programmatically manage permissions. If you are interested in learning more about the technical specifications, you can click the button below. Check out the DAC API specification!

  Documentation access/data-access-committee/dac-portal

• Exome-sequencing identifies new oncogenes and tumor suppressor genes recurrently altered in hepatocellular carcinoma

  Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. High-resolution copy number analysis of 125 tumors of which 24 were subjected to whole-exome sequencing identified 135 homozygous deletions and 994 somatic gene mutations with predicted functional consequences. We identified new recurrent alterations in 4 genes (ARID1A, RPS6KA3, NFE2L2 and IRF2) not previously described in HCC. Functional analyses demonstrated tumor suppressor properties for IRF2 whose inactivation, exclusively found in hepatitis B virus related tumors, leads to impaired TP53 function. Alternatively, inactivation of proteins involved in chromatin remodeling was frequent and predominant in alcohol related tumors. Moreover, activation of the oxidative stress metabolism and inactivation of RPS6KA3 were new pathways associated with WNT/beta-catenin activation, thereby suggesting a cooperative effect in tumorigenesis. This study shows the dramatic somatic genetic diversity in HCC, it reveals interactions between oncogene and tumor suppressor gene mutations markedly related to specific risk factors.

  Study EGAS00001000217

• Single Cell Transcriptomic Data from CD4+ T Cells from Children with MIS-C

  Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infections in the pediatric population characterized by fever, multi-organ involvement and systemic inflammation. Single-cell RNA sequencing was used to evaluate the transcriptomic signature of CD4+ T cells obtained from the peripheral blood of patients with MIS-C before (n=3) and after (n=5) immunomodulatory treatment, along with pediatric controls (n=4). Compared to controls and treated children with MIS-C, T cells obtained from pre-treatment MIS-C patients upregulated genes associated with activation, such as NF-kB signaling. This single-cell transcriptomic data was used in the context of a larger study entitled, "Notch1-CD22-Dependent Immune Dysregulation in the SARSCoV2-Associated Multisystem Inflammatory Syndrome in Children."

  Study phs003086

• Genome-Wide Association Study of HCC in Non-Asian USA Population

  This GWAS of HCC relied on existing biological and data resources from 7 USA sites and one Canadian site which allows for the integration of genetic and environmental data. Total of 2199 case patients and 1103 non cancer controls were genotyped. Case patients are defined as patients with pathological or radiological diagnosis of HCC with and without chronic hepatitis C virus infection. Study was restricted to Caucasian population without prior infection with chronic HBV infection. All DNA samples were extracted from peripheral blood. Study population of the participated sites are: Site-1: University of Texas MD Anderson Cancer Center A hospital based-case-control study was initiated at UT MD Anderson Cancer Center in 2000 and approved by the Institutional Review Board of The University of Texas M. D. Anderson Cancer Center. Study design was previously described in detailed (1-3). Written informed consent for an interview and for a biological sample was obtained from each participant. At time of diagnosis prior to treatment exposure. Case patients were recruited from the population of patients with newly diagnosed HCC who were evaluated and treated at the institution's gastrointestinal medical and surgical oncology outpatient clinics. Inclusion criteria were as follows: a pathologically confirmed diagnosis of HCC, U.S. residency, and the ability to communicate in English. Patients with concurrent or past history of other types of cancers were excluded. Control subjects were healthy spouses of patients with cancers other than liver, gastrointestinal, lung, or head and neck (smoking-related cancers) undergoing treatment at our institution. Eligibility criteria for control subjects were the same as those for patients, except that control subjects could not have ever had cancer. A short, structured questionnaire was used to screen potential control subjects on the basis of eligibility criteria. Control subjects and patients were recruited simultaneously. Case patients and control subjects were interviewed by well-trained interviewers who followed a written protocol to guide ascertainment and reduce surveillance, interviewer, and recall bias. No proxy interviews were conducted. The interviewers used a structured and validated questionnaire to collect information about demographic characteristics and potential risk factors for HCC such as personal smoking history, alcohol use, medical history, occupational history, and family history of cancer. Blood samples from cases and controls were tested for HBV and HCV. HCV antibodies, hepatitis B surface antigen, and antibodies to hepatitis B core antigen were detected by use of a third-generation enzyme-linked immunosorbent assay (ELISA) (Abbott Laboratories, North Chicago, IL). Important clinical information were retrieved from patients' medical records. Total of 1188 case patients and 278 controls from MD Anderson study were genotyped. Site-2: Mayo Clinic Case patients and controls included in the study from Mayo clinic were recruited as part of Mayo International Hepatobiliary Neoplasia Register and Biorepository. Only USA patients and controls were participated. All cases and controls signed informed consent indicating their willingness to participate in genetic studies. Epidemiological and clinical data were collected from participants and retrieved from medical records. Total of 522 HCC case patients and 182 controls were genotyped in this study. Site-3: Toronto University Molecular Epidemiology of Hepatobiliary Tumors (HBT study, CAPCR 09-0289) is a hospital-based study that includes 1710 patients diagnosed with liver, bile duct or gallbladder adenocarcinoma (Hepatocellular carcinoma - HCC; cholangiocarcinoma - CCA; and gall bladder adenocarcinoma -GBCa) recruited at University Health Network (UHN) between 2009 and 2018. HBT study is a prospective study of cancer patients that collects self-reported demographic and epidemiological data, medical records/clinical information and blood samples for research purposes. Eligible patients recruited between 2009 and March 15 2016 were selected to participate in the Genome-Wide Association Study in Patients with Hepatocellular Carcinoma (GWAS in HCC, CAPCR 15-9943-CE), a sub-study of the HBT study. Eligible prospective patients recruited after March 15 2016 signed the Addendum to the HBT consent form and became eligible to participate in the GWAS in HCC study. Total of 271 cases and 21 controls were genotyped from Toronto University Site-4: University of Pittsburgh The design of the study has been described previously (4-6). Briefly, this population-based study enrolled 120 HCC patients and 230 matched controls from black, Hispanic, and non-Hispanic white residents of Los Angeles County who were between 18 and 74 years of age at diagnosis from January 1995 through December 2001. HCC Cases were identified through the Los Angeles County Cancer Surveillance Program. We sought to recruit up to two control subjects per case from the neighborhoods where HCC patients resided at the time of diagnosis, who were matched to the index case by sex, age (within 5 years), and race (Hispanic white, non-Hispanic white, black). Blood samples (plasma and buffy coat), medical and lifestyle factors were collected from all consenting participants. Total of 65 cases and 60 controls were genotyped in this study Site-5: South Western Dallas Under IRB approval, HCC Cases and controls were prospectively collected since 2015 from the outpatient Liver clinics from Parkland Health and Hospital System and UT Southwestern Medical Center, two large health systems in Dallas TX. A Total of 31 cases and 29 controls were genotyped from site 5. Site-6: Columbia University HCC patients from Columbia are those recruited as part of the Herbert Irving Comprehensive Cancer Center Database Shared Resource which seeks to recruit all cancer patients for potential future studies. The PI is Dr. Katherine Crew AAAL5871. This resource collects sociodemographic, lifestyle and clinical data on patients as well as a blood sample. Those who indicated on their consent form that they would participate in genetic studies were included. Total of 79 case patients with HCC were genotyped from Columbia University. Site-7: University of Michigan The study population included from University of Michigan were included from a prospective study of with chronic HCV infection recruited in Ann Arbor Patients who had under- gone liver transplantation, known coinfection with HIV, life expectancy <12 months due to extra-hepatic illnesses, or were receiving HCV treatment at enrolment, were excluded. Protocol, surveys, and data forms were developed where each enrolled patient completed the same questionnaire All patients provided written informed consent before enrolment in the study. The study was approved by the institutional review board or ethics committee at the University of Michigan. Detailed study description was previously published (7). Total of 44 cases and 347 controls were genotyped Site-8: Veteran Administration Medical Center in Houston This research including written informed consent form was jointly approved by Institutional Review Boards for the Baylor College of Medicine and the Michael E. DeBakey VA Medical Center in Houston, Texas. Study details have been previously published (8). Briefly, we prospectively recruited consecutive HCV-infected veterans prior to their previously scheduled HCV clinic visit at a large tertiary care VA medical center between May 1, 2009 and December 31, 2012. Patients completed a research assistant (RA) administered survey interrogating medical and risk factor history including lifetime alcohol use, had anthropometric measurements taken, and completed a fasting venipuncture for performance of the FibroSure-ActiTest as a measure of hepatic pathology. We restricted our current analysis to individuals who were: (1) White male veterans between 18 and 70 years; (2) had no history of HCC, liver transplant, decompensated liver disease including ascites, dementia, or psychosis; (3) were serologically-confirmed to have chronic HCV and to be negative for both HIV and active HBV infection; (4) were not currently receiving anti-HCV pharmacotherapy; and (5) had FibroSURE testing shown F3/F4 fibrosis consistent with cirrhosis.

  Study phs001744

• Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines

  Pneumococcal Vaccine Study: This is a study designed to develop a detailed transcriptional and cellular profile of the immune response to pneumococcal vaccination with conjugated and non-conjugated polysaccharide vaccines in the senescent immune system of older adults. In this study, 39 healthy adults ages 60 and older that have never received pneumococcal vaccination, have been randomized to receive Prevnar 13 (Pfizer), a conjugated 13-valent vaccine or Pneumovax 23 (Merck), a non-conjugated 23-valent vaccine. Four (4) study visits occurred over 70 days at Day -7 (baseline), day 1, day 10 and day 60 (± 5d) post vaccination.Bulk RNA-sequencing data are available on the 4 time points for 31 of the participants and 1 replicate. ATAC-Doublet Detector Study: We generated single nucleus ATAC-seq (snATAC-seq) data from PBMCs of 2 baseline blood samples from the pneumococcal study. Generated data was then used to benchmark a novel computational method for detecting multiplets in snATAC-seq data, namely, AMULET (https://github.com/UcarLab/AMULET). Multiplets confound downstream analyses by introducing combined epigenomic profiles from 2 or more cells/nuclei. AMULET detects multiplets by using unique snATAC-seq data features that allow it to reliably use read counts to detect multiplets for their removal from data analyses.

  Study phs002361