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Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation.

We profiled CD34+ enriched cells from GCSF mobilized bone marrow samples (n = 4) using single-cell RNA sequencing (10X) with targeted genotyping, and single-cell DNA methylation (RRBS) with single-cell RNA sequencing (Smart-Seq2) and targeted genotyping. A 5th CH bone marrow aspirate sample was obtained to validate observed results.

Request Access

Individuals who wish to download sequencing data for this publication will need approval from the Single-cell Multiomics Clonal Hematopoiesis Data Access Committee and abide by the following rules for data use.

These terms and conditions govern access to the managed access datasets (details of which are set out in Appendix I) to which the User Institution has requested access. The User Institution agrees to be bound by these terms and conditions. Definitions Authorised Personnel: The individuals at the User Institution to whom Single-cell Multiomics Glioma Team Data Access Committee grants access to the Data. This includes the User, the individuals listed in Appendix II and any other individuals for whom the User Institution subsequently requests access to the Data. Details of the initial Authorised Personnel are set out in Appendix II. Data: The managed access datasets to which the User Institution has requested access. Data Producers: Single-cell Multiomics Glioma Team Data Access Committee and the collaborators listed in Appendix I responsible for the development, organisation, and oversight of these Data. External Collaborator: A collaborator of the User, working for an institution other than the User Institution. Project: The project for which the User Institution has requested access to these Data. A description of the Project is set out in Appendix II. Publications: Includes, without limitation, articles published in print journals, electronic journals, reviews, books, posters and other written and verbal presentations of research. Research Participant: An individual whose data form part of these Data. Research Purposes: Shall mean research that is seeking to advance the understanding of genetics and genomics, including the treatment of disorders, and work on statistical methods that may be applied to such research. User: The principal investigator for the Project. User Institution(s): The Institution that has requested access to the Data. Single-cell Multiomics Glioma Team Data Access Committee: Weill Cornell Medicine, Belfer Research Building, 14th Floor, Room 1428, 413 East 69th Street, New York, NY 10021 1. The User Institution agrees to only use these Data for the purpose of the Project (described in Appendix II) and only for Research Purposes. The User Institution further agrees that it will only use these Data for Research Purposes which are within the limitations (if any) set out in Appendix I. 2. The User Institution agrees to preserve, at all times, the confidentiality of these Data. In particular, it undertakes not to use, or attempt to use these Data to compromise or otherwise infringe the confidentiality of information on Research Participants. Without prejudice to the generality of the foregoing, the User Institution agrees to use at least the measures set out in Appendix I to protect these Data. 3. The User Institution agrees to protect the confidentiality of Research Participants in any research papers or publications that they prepare by taking all reasonable care to limit the possibility of identification. 4. The User Institution agrees not to link or combine these Data to other information or archived data available in a way that could re-identify the Research Participants, even if access to that data has been formally granted to the User Institution or is freely available without restriction. 5. The User Institution agrees only to transfer or disclose these Data, in whole or part, or any material derived from these Data, to the Authorised Personnel. Should the User Institution wish to share these Data with an External Collaborator, the External Collaborator must complete a separate application for access to these Data. 6. The User Institution agrees that the Data Producers, and all other parties involved in the creation, funding or protection of these Data: a) make no warranty or representation, express or implied as to the accuracy, quality or comprehensiveness of these Data; b) exclude to the fullest extent permitted by law all liability for actions, claims, proceedings, demands, losses (including but not limited to loss of profit), costs, awards damages and payments made by the Recipient that may arise (whether directly or indirectly) in any way whatsoever from the Recipient’s use of these Data or from the unavailability of, or break in access to, these Data for whatever reason and; c) bear no responsibility for the further analysis or interpretation of these Data. 7. The User Institution agrees to follow the Fort Lauderdale Guidelines (http://www.wellcome.ac.uk/stellent/groups/corporatesite/@policy_communications/documents/web_document/wtd003207.pdf ) and the Toronto Statement (http://www.nature.com/nature/journal/v461/n7261/full/461168a.html). This includes but is not limited to recognising the contribution of the Data Producers and including a proper acknowledgement in all reports or publications resulting from the use of these Data. 8. The User Institution agrees to follow the Publication Policy in Appendix III. This includes respecting the moratorium period for the Data Producers to publish the first peer-reviewed report describing and analysing these Data. 9. The User Institution agrees not to make intellectual property claims on these Data and not to use intellectual property protection in ways that would prevent or block access to, or use of, any element of these Data, or conclusion drawn directly from these Data. 10. The User Institution can elect to perform further research that would add intellectual and resource capital to these data and decide to obtain intellectual property rights on these downstream discoveries. In this case, the User Institution agrees to implement licensing policies that will not obstruct further research and to follow the U.S. National Institutes of Health Best Practices for the Licensing of Genomic Inventions (2005) (https://www.icgc.org/files/daco/NIH_BestPracticesLicensingGenomicInventions_2005_en.pdf ) in conformity with the Organisation for Economic Co-operation and Development Guidelines for the Licensing of the Genetic Inventions (2006) (http://www.oecd.org/science/biotech/36198812.pdf ). 11. The User Institution agrees to destroy/discard the Data held, once it is no longer used for the Project, unless obliged to retain the data for archival purposes in conformity with audit or legal requirements. 12. The User Institution will notify Single-cell Multiomics Glioma Team Data Access Committee within 30 days of any changes or departures of Authorised Personnel. 13. The User Institution will notify Single-cell Multiomics Glioma Team Data Access Committee prior to any significant changes to the protocol for the Project. 14. The User Institution will notify Single-cell Multiomics Glioma Team Data Access Committee as soon as it becomes aware of a breach of the terms or conditions of this agreement. 15. Single-cell Multiomics Glioma Team Data Access Committee may terminate this agreement by written notice to the User Institution. If this agreement terminates for any reason, the User Institution will be required to destroy any Data held, including copies and backup copies. This clause does not prevent the User Institution from retaining these data for archival purpose in conformity with audit or legal requirements. 16. The User Institution accepts that it may be necessary for the Data Producers to alter the terms of this agreement from time to time. As an example, this may include specific provisions relating to the Data required by Data Producers other than Single-cell Multiomics Glioma Team Data Access Committee. In the event that changes are required, the Data Producers or their appointed agent will contact the User Institution to inform it of the changes and the User Institution may elect to accept the changes or terminate the agreement. 17. If requested, the User Institution will allow data security and management documentation to be inspected to verify that it is complying with the terms of this agreement. 18. The User Institution agrees to distribute a copy of these terms to the Authorised Personnel. The User Institution will procure that the Authorised Personnel comply with the terms of this agreement. APPENDIX I – DATASET DETAILS (to be completed by the data producer before passing to applicant) Dataset reference (EGA Study ID and Dataset Details) Name of project that created the dataset Names of other data producers/collaborators Specific limitations on areas of research Minimum protection measures required File access: Data can be held in unencrypted files on an institutional compute system, with Unix user group read/write access for one or more appropriate groups but not Unix world read/write access behind a secure firewall. Laptops holding these data should have password protected logins and screenlocks (set to lock after 5 min of inactivity). If held on USB keys or other portable hard drives, the data must be encrypted. APPENDIX II – PROJECT DETAILS (to be completed by the Requestor) Details of dataset requested i.e., EGA Study and Dataset Accession Number Brief abstract of the Project in which the Data will be used (500 words max) All Individuals who the User Institution to be named as registered users (Name of Registered User, Email, Job Title, Supervisor) All Individuals that should have an account created at the EGA (Name of Registered User, Email, Job Title) APPENDIX III – PUBLICATION POLICY Single-cell Multiomics Glioma Team Data Access Committee intend to publish the results of their analysis of this dataset and do not consider its deposition into public databases to be the equivalent of such publications. Single-cell Multiomics Glioma Team Data Access Committee anticipate that the dataset could be useful to other qualified researchers for a variety of purposes. However, some areas of work are subject to a publication moratorium. The publication moratorium covers any publications (including oral communications) that describe the use of the dataset. For research papers, submission for publication should not occur until 3 months after these data were first made available on the relevant hosting database, unless Single-cell Multiomics Glioma Team Data Access Committee has provided written consent to earlier submission. In any publications based on these data, please describe how the data can be accessed, including the name of the hosting database (e.g., The European Genome-phenome Archive at the European Bioinformatics Institute) and its accession numbers (e.g., EGAS00000000029), and acknowledge its use in a form agreed by the User Institution with Single-cell Multiomics Glioma Team Data Access Committee.

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
Cancer Genomics

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
EGAF00006215206 1655507776358 267.2 MB
EGAF00006215207 1655507776358 371.4 MB
EGAF00006215208 1655511321071 7.6 GB
EGAF00006215209 1655511321070 17.7 GB
EGAF00006215210 1655507776358 210.1 kB
EGAF00006215211 1655507776358 324.5 kB
EGAF00006215212 1655507776358 719.8 kB
EGAF00006215213 1655507776358 673.6 kB
EGAF00006215214 1655507776358 857.8 kB
EGAF00006215215 1655507776358 869.3 kB
EGAF00006215216 1655507776358 59.0 kB
EGAF00006215217 1655507776358 59.2 kB
EGAF00006215218 1655507776358 1.9 MB
EGAF00006215219 1655507776358 1.9 MB
EGAF00006215220 1655507776358 43.5 kB
EGAF00006215221 1655507776358 43.4 kB
EGAF00006215222 1655507776358 51.4 kB
EGAF00006215223 1655507776358 51.1 kB
EGAF00006215224 1655507776358 62.4 kB
EGAF00006215225 1655507776358 63.7 kB
EGAF00006215226 1655507776358 959.5 kB
EGAF00006215227 1655507776358 944.3 kB
EGAF00006215228 1655507776358 925.0 kB
EGAF00006215229 1655507776358 913.6 kB
EGAF00006215230 1655507776358 473.6 kB
EGAF00006215231 1655507776358 796.7 kB
EGAF00006215232 1655507776358 258.0 kB
EGAF00006215233 1655507776358 255.7 kB
EGAF00006215234 1655507776358 2.8 MB
EGAF00006215235 1655507776358 2.6 MB
EGAF00006215236 1655507776358 1.6 MB
EGAF00006215237 1655507776358 1.5 MB
EGAF00006215238 1655507776358 724.0 kB
EGAF00006215239 1655507776358 677.6 kB
EGAF00006215240 1655507776358 173.5 kB
EGAF00006215241 1655507776358 296.5 kB
EGAF00006215242 1655507776358 521.4 kB
EGAF00006215243 1655507776358 495.5 kB
EGAF00006215244 1655507776358 235.5 kB
EGAF00006215245 1655507776358 238.5 kB
EGAF00006215246 1655507776358 902.2 kB
EGAF00006215247 1655507776358 873.5 kB
EGAF00006215248 1655507776358 2.3 MB
EGAF00006215249 1655507776358 2.2 MB
EGAF00006215250 1655507776358 176.5 kB
EGAF00006215251 1655507776358 172.4 kB
EGAF00006215252 1655507776358 34.6 kB
EGAF00006215253 1655507776358 34.6 kB
EGAF00006215254 1655507776358 52.8 kB
EGAF00006215255 1655507776358 51.7 kB
EGAF00006215256 1655507776358 20.3 kB
EGAF00006215257 1655507776358 20.2 kB
EGAF00006215258 1655507776357 1.8 MB
EGAF00006215259 1655507776357 1.8 MB
EGAF00006215260 1655507776357 375.5 kB
EGAF00006215261 1655507776357 381.0 kB
EGAF00006215262 1655507776357 912.9 kB
EGAF00006215263 1655507776357 962.9 kB
EGAF00006215264 1655507776357 215.3 kB
EGAF00006215265 1655507776357 215.1 kB
EGAF00006215266 1655507776357 593.4 kB
EGAF00006215267 1655507776357 582.5 kB
EGAF00006215268 1655507776358 340.3 kB
EGAF00006215269 1655507776357 344.6 kB
EGAF00006215270 1655507776357 45.4 kB
EGAF00006215271 1655507776357 43.5 kB
EGAF00006215272 1655507776357 53.1 kB
EGAF00006215273 1655507776358 52.8 kB
EGAF00006215274 1655507776358 183.4 kB
EGAF00006215275 1655507776358 184.0 kB
EGAF00006215276 1655507776358 361.9 kB
EGAF00006215277 1655507776358 351.0 kB
EGAF00006215278 1655507776358 1.1 MB
EGAF00006215279 1655507776358 1.1 MB
EGAF00006215280 1655507776358 1.3 MB
EGAF00006215281 1655507776358 1.3 MB
EGAF00006215282 1655507776358 18.7 kB
EGAF00006215283 1655507776358 17.7 kB
EGAF00006215284 1655507776358 457.5 kB
EGAF00006215285 1655507776358 459.7 kB
EGAF00006215286 1655507776358 90.7 kB
EGAF00006215287 1655507776358 137.1 kB
EGAF00006215288 1655507776358 991.5 kB
EGAF00006215289 1655507776358 972.8 kB
EGAF00006215290 1655507776358 1.7 MB
EGAF00006215291 1655507776358 1.7 MB
EGAF00006215292 1655507776358 97.5 kB
EGAF00006215293 1655507776358 97.1 kB
EGAF00006215294 1655507776358 26.7 kB
EGAF00006215295 1655507776358 25.3 kB
EGAF00006215296 1655507776358 408.7 kB
EGAF00006215297 1655507776358 408.6 kB
EGAF00006215298 1655507776358 255.6 kB
EGAF00006215299 1655507776358 252.1 kB
EGAF00006215300 1655507776358 236.0 kB
EGAF00006215301 1655507776358 227.0 kB
EGAF00006215302 1655507776358 31.0 kB
EGAF00006215303 1655507776358 29.3 kB
EGAF00006215304 1655507776357 37.3 kB
EGAF00006215305 1655507776357 35.9 kB
EGAF00006215306 1655507776357 839.5 kB
EGAF00006215307 1655507776357 832.4 kB
EGAF00006215308 1655507776357 2.8 MB
EGAF00006215309 1655507776358 2.7 MB
EGAF00006215310 1655507776358 211.2 kB
EGAF00006215311 1655507776357 212.7 kB
EGAF00006215312 1655507776357 38.6 kB
EGAF00006215313 1655507776357 37.1 kB
EGAF00006215314 1655507776357 238.4 kB
EGAF00006215315 1655507776357 234.1 kB
EGAF00006215316 1655507776357 40.5 kB
EGAF00006215317 1655507776357 40.3 kB
EGAF00006215318 1655507776357 42.8 kB
EGAF00006215319 1655507776357 42.5 kB
EGAF00006215320 1655507776357 38.6 kB
EGAF00006215321 1655507776357 38.0 kB
EGAF00006215322 1655507776357 42.1 kB
EGAF00006215323 1655507776357 40.9 kB
EGAF00006215324 1655507776357 820.1 kB
EGAF00006215325 1655507776357 778.4 kB
EGAF00006215326 1655507776357 868.7 kB
EGAF00006215327 1655507776357 843.7 kB
EGAF00006215328 1655507776358 14.6 kB
EGAF00006215329 1655507776358 13.9 kB
EGAF00006215330 1655507776357 28.1 kB
EGAF00006215331 1655507776357 27.0 kB
EGAF00006215332 1655507776357 600.1 kB
EGAF00006215333 1655507776357 586.5 kB
EGAF00006215334 1655507776357 24.5 kB
EGAF00006215335 1655507776357 23.5 kB
EGAF00006215336 1655507776357 1.1 MB
EGAF00006215337 1655507776357 811.6 kB
EGAF00006215338 1655507776357 56.0 kB
EGAF00006215339 1655507776357 54.4 kB
EGAF00006215340 1655507776357 143.3 kB
EGAF00006215341 1655507776357 144.4 kB
EGAF00006215342 1655507776357 174.9 kB
EGAF00006215343 1655507776357 168.4 kB
EGAF00006215344 1655507776357 486.2 kB
EGAF00006215345 1655507776357 472.3 kB
EGAF00006215346 1655507776357 25.9 kB
EGAF00006215347 1655507776357 24.6 kB
EGAF00006215348 1655507776357 46.8 kB
EGAF00006215349 1655507776357 45.2 kB
EGAF00006215350 1655507776357 32.7 kB
EGAF00006215351 1655507776357 31.2 kB
EGAF00006215352 1655507776358 26.6 kB
EGAF00006215353 1655507776357 25.6 kB
EGAF00006215354 1655507776357 1.9 MB
EGAF00006215355 1655507776357 1.8 MB
EGAF00006215356 1655507776357 29.3 kB
EGAF00006215357 1655507776357 28.8 kB
EGAF00006215358 1655507776357 28.7 kB
EGAF00006215359 1655507776357 27.4 kB
EGAF00006215360 1655507776357 109.9 kB
EGAF00006215361 1655507776357 107.2 kB
EGAF00006215362 1655507776357 39.2 kB
EGAF00006215363 1655507776357 37.6 kB
EGAF00006215364 1655507776357 659.8 kB
EGAF00006215365 1655507776358 676.4 kB
EGAF00006215366 1655507776358 771.0 kB
EGAF00006215367 1655507776358 732.0 kB
EGAF00006215368 1655507776358 346.4 kB
EGAF00006215369 1655507776358 314.1 kB
EGAF00006215370 1655507776358 96.9 kB
EGAF00006215371 1655507776358 95.3 kB
EGAF00006215372 1655507776358 439.0 kB
EGAF00006215373 1655507776358 422.1 kB
EGAF00006215374 1655507776358 1.0 MB
EGAF00006215375 1655507776358 973.4 kB
EGAF00006215376 1655507776358 45.1 kB
EGAF00006215377 1655507776358 43.9 kB
EGAF00006215378 1655507776358 29.0 kB
EGAF00006215379 1655507776358 26.7 kB
EGAF00006215380 1655507776358 30.3 kB
EGAF00006215381 1655507776358 28.4 kB
EGAF00006215382 1655507776358 40.6 kB
EGAF00006215383 1655507776358 36.0 kB
EGAF00006215384 1655507776358 41.4 kB
EGAF00006215385 1655507776358 39.9 kB
EGAF00006215386 1655507776358 47.9 kB
EGAF00006215387 1655507776358 46.7 kB
EGAF00006215388 1655507776358 427.4 kB
EGAF00006215389 1655507776358 435.2 kB
EGAF00006215390 1655507776358 128.3 kB
EGAF00006215391 1655507776358 127.5 kB
EGAF00006215392 1655507776358 33.7 kB
EGAF00006215393 1655507776358 33.1 kB
EGAF00006215394 1655507776358 25.1 kB
EGAF00006215395 1655507776357 24.2 kB
EGAF00006215396 1655507776357 32.2 kB
EGAF00006215397 1655507776357 29.3 kB
EGAF00006215398 1655507776357 26.4 kB
EGAF00006215399 1655507776357 24.0 kB
EGAF00006215400 1655507776357 326.2 kB
EGAF00006215401 1655507776357 320.0 kB
EGAF00006215402 1655508678508 2.1 GB
EGAF00006215403 1655507776357 2.3 GB
EGAF00006215404 1655508678508 3.0 GB
EGAF00006215405 1655509526330 3.2 GB
EGAF00006215406 1655508678508 1.8 GB
EGAF00006215407 1655509526330 1.9 GB
EGAF00006215408 1655508678508 2.1 GB
EGAF00006215409 1655508678508 2.2 GB
EGAF00006215410 1655507776357 30.7 MB
EGAF00006215411 1655507776357 31.1 MB
EGAF00006215412 1655507776357 24.8 MB
EGAF00006215413 1655507776357 25.6 MB
EGAF00006215414 1655507776357 31.1 MB
EGAF00006215415 1655507776357 32.1 MB
EGAF00006215416 1655507776357 35.2 MB
EGAF00006215417 1655507776358 36.3 MB
EGAF00006215418 1655507776358 32.7 MB
EGAF00006215419 1655507776358 33.2 MB
EGAF00006215420 1655507776358 24.4 MB
EGAF00006215421 1655507776358 25.3 MB
EGAF00006215422 1655507776358 29.1 MB
EGAF00006215423 1655507776358 29.8 MB
EGAF00006215424 1655507776358 30.0 MB
EGAF00006215425 1655507776358 30.9 MB
EGAF00006215426 1655507776358 26.1 MB
EGAF00006215427 1655507776358 27.1 MB
EGAF00006215428 1655507776358 27.5 MB
EGAF00006215429 1655507776358 28.2 MB
EGAF00006215430 1655507776358 30.4 MB
EGAF00006215431 1655507776358 31.1 MB
EGAF00006215432 1655507776358 25.8 MB
EGAF00006215433 1655507776358 26.5 MB
EGAF00006215434 1655507776358 28.5 MB
EGAF00006215435 1655507776358 28.7 MB
EGAF00006215436 1655507776358 19.8 MB
EGAF00006215437 1655507776358 20.2 MB
EGAF00006215438 1655507776358 28.3 MB
EGAF00006215439 1655507776358 29.0 MB
EGAF00006215440 1655507776358 33.0 MB
EGAF00006215441 1655507776358 33.2 MB
EGAF00006215442 1655507776358 28.6 MB
EGAF00006215443 1655507776358 28.6 MB
EGAF00006215444 1655507776358 30.0 MB
EGAF00006215445 1655507776358 31.0 MB
EGAF00006215446 1655507776358 29.0 MB
EGAF00006215447 1655507776358 29.4 MB
EGAF00006215448 1655507776357 26.3 MB
EGAF00006215449 1655507776357 27.1 MB
EGAF00006215450 1655507776357 23.7 MB
EGAF00006215451 1655507776357 23.6 MB
EGAF00006215452 1655507776357 26.2 MB
EGAF00006215453 1655507776357 26.6 MB
EGAF00006215454 1655507776357 28.1 MB
EGAF00006215455 1655507776357 28.3 MB
EGAF00006215456 1655507776357 26.0 MB
EGAF00006215457 1655507776358 26.7 MB
EGAF00006215458 1655507776358 19.7 MB
EGAF00006215459 1655507776357 19.7 MB
EGAF00006215460 1655507776357 18.4 MB
EGAF00006215461 1655507776357 18.9 MB
EGAF00006215462 1655507776357 26.4 MB
EGAF00006215463 1655507776357 27.1 MB
EGAF00006215464 1655507776357 32.3 MB
EGAF00006215465 1655507776357 32.4 MB
EGAF00006215466 1655507776357 24.2 MB
EGAF00006215467 1655507776357 24.5 MB
EGAF00006215468 1655507776357 25.9 MB
EGAF00006215469 1655507776357 26.7 MB
EGAF00006215470 1655507776357 23.6 MB
EGAF00006215471 1655507776357 22.3 MB
EGAF00006215472 1655507776357 28.4 MB
EGAF00006215473 1655507776357 29.5 MB
EGAF00006215474 1655507776357 27.7 MB
EGAF00006215475 1655507776357 27.6 MB
EGAF00006215476 1655507776357 24.9 MB
EGAF00006215477 1655507776357 25.0 MB
EGAF00006215478 1655507776357 27.5 MB
EGAF00006215479 1655507776357 28.1 MB
EGAF00006215480 1655507776357 27.1 MB
EGAF00006215481 1655507776357 27.7 MB
EGAF00006215482 1655507776357 23.4 MB
EGAF00006215483 1655507776358 24.0 MB
EGAF00006215484 1655507776358 19.4 MB
EGAF00006215485 1655507776357 20.0 MB
EGAF00006215486 1655507776357 24.3 MB
EGAF00006215487 1655507776357 25.1 MB
EGAF00006215488 1655507776357 25.0 MB
EGAF00006215489 1655507776357 25.6 MB
EGAF00006215490 1655507776357 12.0 MB
EGAF00006215491 1655507776357 12.1 MB
EGAF00006215492 1655507776357 19.9 MB
EGAF00006215493 1655507776357 20.6 MB
EGAF00006215494 1655507776357 25.0 MB
EGAF00006215495 1655507776357 25.6 MB
EGAF00006215496 1655507776357 15.7 MB
EGAF00006215497 1655507776357 16.1 MB
EGAF00006215498 1655507776357 20.1 MB
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1456 Files (326.5 GB)