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Extreme phenotypes define epigenetic and metabolic signatures in cardiovascular diseases

Improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis are ongoing healthcare challenges. Using plasma biomarkers analysis coupled with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (obese and lipodystrophy) and comparing these to lean individuals and blood donors, the present study identifies the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells and shows that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers. The characterisation of the same obese group, six months after bariatric surgery shows the loss of the patterns of abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individuals, this occurs via the establishment of novel gene expression landscapes. Netosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention. Taken together, by integrating across data layers, the observed molecular and metabolic differences form a disease signature that is able to discriminate, amongst the blood donors, those individuals with a higher likelihood of having cardiometabolic syndrome, even when not presenting with the classic features.

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Data access commitee regulating access to data generated in Seyres et al. 2021, including H3K27ac, RRBS and RNAseq in monocytes, neutrophils, platelets and macrophages of people presenting an extreme phenotype.

Thank you for your interest in the datasets generated by the EPomes (Extreme Phenotype omics) consortium. To apply for access, please submit a brief research proposal (no more than one page) and a signed Data Access Agreement to m.frontini@exeter.ac.uk. Your application will then be considered by the Data Access Committee. If successful, you will receive a link to the raw data on EGA for the requested accessions. Who should sign the Data Access Agreement? The immediate users of the data and the principal investigator / lab head should sign “for and on behalf of User”. The user institution’s official contact (typically the Technology Transfer Officer) should sign (and ideally stamp) “for and on behalf of User Institution”. If you have any further questions, please email m.frontini@exeter.ac.uk.   Dataset accession number(s) requested: Research proposal:   EPomes CONSORTIUM DATA ACCESS AGREEMENT This agreement governs the terms on which access will be granted through the Data Access Committee (DAC) to the data (RNA-sequencing, ChIP-sequencing, RRBS-sequencing) available in the European Genome- phenome Archive (EGA) by the European Bioinformatics Institute, the UK Outstation of the European Molecular Biology Laboratory for and mandated by the members of the PCHI-C Consortium. In signing this agreement, you are agreeing to be bound by the terms and conditions of access set out in this agreement. For the sake of clarity, the terms of access set out in this agreement apply both to the User and the User’s Institution (as defined below). User Institution and User are referred to within the agreement as “You” and “Your” shall be construed accordingly. Definitions: The DAC means the Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes consortium that manage access to all data submitted by it to the EGA. EPomes consortium means the consortium of researchers involved in the generation and analysis of the dataset described in the manuscript “Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes consortium” in currently on BioRxiv. EGA means the European Genome-phenome Archive, a permanent archive of controlled access data generated for biomedical research and deposited to enable data sharing. The EGA is described on the website http://www.ebi.ac.ukl/ega. Data means all and any human genetic or phenotype data obtained from the EGA.
Data Subject means a person, who has been informed of the purpose for which the Data is held and has given his/her informed consent thereto. User means a researcher whose User Institution has previously completed this Data Access Agreement and has received acknowledgement of its acceptance. Publications means, without limitation, articles published in print journals, electronic journals, reviews, books, posters and other written and verbal presentations of research, including social media. User Institution means the organisation at which the User is employed, affiliated or enrolled. Terms and Conditions: In signing this Agreement: 1. You agree to use the Data only for the advancement of medical research and according to the consent obtained from sample donors. 
 2. You agree to preserve, at all times, the confidentiality of information and Data pertaining to Data Subjects. In particular, You undertake not to identify or attempt to identify any Data Subject. 
 3. You agree not to attempt to link the data provided under this agreement to other information or archive data available for the data sets provided, even if access to that data has been formally granted to you, or it is freely available without restriction, without specific permission being sought from the relevant access committees. 4. You agree not to transfer or disclose the Data, in whole or part, or any identifiable material derived from the Data, to others, except as necessary for data/safety monitoring or programme management. Should You wish to share the Data with a collaborator outwith the same Institution, the third party must make a separate application for access to the Data. 
 5. You agree to use the data for the approved purpose and project described in your application; use of the data for a new purpose or project will require a new application and approval. 
 6. You accept that Data will be updated from time to time, with suitable versioning. If the reissue is at the request of sample donors and/or other ethical scrutiny, You will destroy earlier versions of the Data. 
 7. You accept that the DAC, the Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes consortium Consortium, or the funders of the Data or any part of the Data supplied: 
a) bear no legal responsibility for the accuracy or comprehensiveness of the Data; and
b) accept no liability for indirect, consequential, or incidental, damages or losses arising from use of the Data, or from the unavailability of, or break in access to, the Data for whatever reason. 
 8. You understand and acknowledge that the Data may be protected by copyright and other intellectual property rights, and that duplication, except as reasonably required to carry out Your research with the Data, or sale of all or part of the Data on any media may not be permitted. Users of the data are solely responsible for establishing the nature of and complying with any such intellectual property restrictions. 
 9. You recognise that nothing in this agreement shall operate to transfer to the User Institution any intellectual property rights relating to the Data. The User Institution has the right to develop intellectual property based on comparisons with their own data. 
 10. You accept that this agreement will terminate immediately upon any breach of this agreement by You and You will be required to destroy any Data held. 
 11. You accept that it may be necessary for the Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes consortium Consortium or its appointed agent to alter the terms of this agreement from time to time in order to address new concerns. In this event, the EGA or its appointed agent will contact You to inform You of any changes and You agree that Your continued use of the Data shall be dependent on the parties entering into a new version of the Agreement. 
 12. You agree that you will submit a report to the DAC, if requested, on completion of the agreed purpose. The DAC agrees to treat the report and all information, data, results, and conclusions contained within such report as confidential information belonging to the User Institution. 
 13. You accept that the Data may be protected by and subject to international laws, including but not limited to applicable laws on the protection of personal data, and that You are responsible for ensuring compliance with any such applicable law. You undertake to implement or have implemented adequate technical and organisational security measures to protect Data. The DAC reserves the right to request and inspect data security and management documentation to ensure the adequacy of data protection measures, particularly in countries that have no national laws comparable to those which pertain in the EEA. 
 DAA ver1, 2021 For and on behalf of User Name of Applicant(s): Signature of Applicant(s): Date: For and on behalf of User Institution Signature of Institutional or Administrative Authority: Print name: User Institution: Date: WHEN SUBMITTING THIS DOCUMENT, PLEASE INCLUDE ALL PAGES OF THE AGREEMENT WITH THIS SIGNATURE PAGE   APPENDIX 1 Publications Policy The Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes Consortium anticipates that data generated from the project will be used by others, such as required for developing new analytical methods, in understanding epigenetics, for integrative analysis and for other uses. Authors who use data from the project must acknowledge the Consortium using the following wording "This study makes use of data generated by the Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes Consortium. A full list of the investigators who contributed to the generation of the data is available in “Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes consortium” BioRxiv. Users must also cite the primary publication mentioned above. Users should note that the Consortium bears no responsibility for the further analysis or interpretation of these data, over and above that published by the Consortium. DAA ver1, 2021

Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001003780 Other

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
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815 Files (2.1 TB)