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Multiregional single nuclei RNA-seq and WGS of prostate cancer

This study investigates the clonal evolution and metastatic dissemination of prostate cancer using multiregional single-nuclei RNA sequencing (snRNA-seq) and low-pass whole-genome sequencing (WGS) data from 43 spatially distinct tumor areas in five patients with locally advanced prostate cancer, including both primary and regional lymph node samples. We employed the Chromium Next GEM Single Cell 3’ Kit (v3/3.1, 10x Genomics) for single-nuclei transcriptome profiling and constructed bulk WGS libraries using the NEBNext Ultra II FS DNA Library Prep Kit (New England Biolabs) from the same pool of nuclei extracted from each area. snRNA-seq data were aligned to the human genome (GRCh38-1.2.0_premrna) using 10x Genomics Cell Ranger v5.0.0, while WGS reads were aligned to the human reference genome (GRCh38) with BWA MEM, achieving an average sequencing depth of 0.3X for low-pass WGS and 16X after resequencing.

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Data Access Policy for Genomic Data

DATA ACCESS AGREEMENT 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 Rigshospitalet 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: Rigshospitalet 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. Rigshospitalet: Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark 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/w eb_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 Rigshospitalet within 30 days of any changes or departures of Authorised Personnel. 13. The User Institution will notify Rigshospitalet prior to any significant changes to the protocol for the Project. 14. The User Institution will notify Rigshospitalet as soon as it becomes aware of a breach of the terms or conditions of this agreement. 15. Rigshospitalet 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 Rigshospitalet. 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. 19. This agreement (and any dispute, controversy, proceedings or claim of whatever nature arising out of this agreement or its formation) shall be construed, interpreted and governed by the laws of Denmark and shall be subject to the exclusive jurisdiction of the Danish courts. Agreed for User Institution Signature: Name: Title: Institute: Address: Date: Principal Investigator I confirm that I have read and understood this Agreement. Signature: Name: Title: Date: Agreed for Rigshospitalet Signature: Name: Title: Date: APPENDIX I – DATASET DETAILS APPENDIX II ––PROJECT DETAILS APPENDIX III –– PUBLICATION POLICY APPENDIX I – DATASET DETAILS (to be completed by the data producer before passing to applicant) Dataset reference (EGA Study ID and Dataset Details) EGAS50000000927 Name of project that created the dataset Clonal Evolution and Transcriptional Plasticity Shape Metastatic Dissemination Routes in Prostate Cancer Names of other data producers/collaborators Migle Mikutenaite, Evdoxia Karadoulama, Francesco Favero, Alessio Locallo, Francisco German Rodriguez Gonzalez, Daria Kiriy, Tina Keshavarzian, Kira Furlano, Markus Graefen, Robert G Bristow, Clarissa Gerhäuser, Christoph Plass, Guido Sauter, Ronald Simon, Mathieu Lupien, Sarah Minner, Thorsten Schlomm, Joachim Weischenfeldt Specific limitations on areas of research None Minimum protection measures required Successful applicants should have access to a secure server. The dataset, or any data which relates to it containing sensitive genetic information, should remain on this server. Applicants should also provide a list of individuals who will have access to the dataset. 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 Rigshospitalet 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. Rigshospitalet 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 12 months after these data were first made available on the relevant hosting database, unless Rigshospitalet 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 Rigshospitalet.

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
EGAS50000000927 Transcriptome Sequencing

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 Quality Report
Located in
EGAF50000330305 cram 56.5 GB
EGAF50000330306 crai 890.1 kB
EGAF50000330307 cram 58.5 GB
EGAF50000330308 crai 1.0 MB
EGAF50000330309 cram 129.5 GB
EGAF50000330310 crai 2.2 MB
EGAF50000330311 cram 49.7 GB
EGAF50000330312 crai 802.4 kB
EGAF50000330313 cram 152.3 GB
EGAF50000330314 crai 2.6 MB
EGAF50000330315 crai 1.0 MB
EGAF50000330316 cram 50.5 GB
EGAF50000330317 cram 53.3 GB
EGAF50000330318 crai 946.4 kB
EGAF50000330319 cram 29.6 GB
EGAF50000330320 crai 508.4 kB
EGAF50000330321 cram 85.1 GB
EGAF50000330322 crai 1.7 MB
EGAF50000330323 cram 65.9 GB
EGAF50000330324 crai 1.2 MB
EGAF50000330325 crai 1.5 MB
EGAF50000330326 cram 82.2 GB
EGAF50000330327 cram 34.4 GB
EGAF50000330328 crai 689.4 kB
EGAF50000330329 cram 55.3 GB
EGAF50000330330 crai 1.0 MB
EGAF50000330331 cram 61.5 GB
EGAF50000330332 crai 1.1 MB
EGAF50000330333 cram 66.1 GB
EGAF50000330334 crai 1.2 MB
EGAF50000330335 cram 124.1 GB
EGAF50000330336 crai 2.1 MB
EGAF50000330337 cram 151.7 GB
EGAF50000330338 crai 2.7 MB
EGAF50000330339 cram 105.1 GB
EGAF50000330340 crai 1.8 MB
EGAF50000330341 crai 1.5 MB
EGAF50000330342 cram 77.3 GB
EGAF50000330343 cram 92.0 GB
EGAF50000330344 crai 1.8 MB
EGAF50000330345 cram 83.9 GB
EGAF50000330346 crai 1.4 MB
EGAF50000330347 cram 95.7 GB
EGAF50000330348 crai 1.8 MB
EGAF50000330349 crai 1.6 MB
EGAF50000330350 cram 85.7 GB
EGAF50000330351 cram 55.6 GB
EGAF50000330352 crai 1.0 MB
EGAF50000330353 cram 108.4 GB
EGAF50000330354 crai 2.3 MB
EGAF50000330355 cram 144.5 GB
EGAF50000330356 crai 2.9 MB
EGAF50000330357 cram 32.7 GB
EGAF50000330358 crai 596.5 kB
EGAF50000330359 crai 1.2 MB
EGAF50000330360 cram 66.8 GB
EGAF50000330361 cram 62.4 GB
EGAF50000330362 crai 1.2 MB
EGAF50000330363 cram 65.5 GB
EGAF50000330364 crai 1.2 MB
EGAF50000330365 cram 44.3 GB
EGAF50000330366 crai 813.7 kB
EGAF50000330367 cram 111.3 GB
EGAF50000330368 crai 1.9 MB
EGAF50000330369 cram 42.7 GB
EGAF50000330370 crai 763.3 kB
EGAF50000330371 cram 56.0 GB
EGAF50000330372 crai 973.8 kB
EGAF50000330373 cram 91.0 GB
EGAF50000330374 crai 1.9 MB
EGAF50000330375 cram 52.0 GB
EGAF50000330376 crai 1.0 MB
EGAF50000330377 cram 73.6 GB
EGAF50000330378 crai 1.5 MB
EGAF50000330379 cram 99.6 GB
EGAF50000330380 crai 1.8 MB
EGAF50000330381 cram 56.4 GB
EGAF50000330382 crai 1.0 MB
EGAF50000330383 cram 58.4 GB
EGAF50000330384 crai 1.0 MB
EGAF50000330385 cram 60.8 GB
EGAF50000330386 crai 1.1 MB
EGAF50000330387 cram 53.1 GB
EGAF50000330388 crai 903.8 kB
EGAF50000330389 cram 40.3 GB
EGAF50000330390 crai 771.7 kB
EGAF50000330391 cram 221.0 MB
EGAF50000330392 crai 38.8 kB
EGAF50000330393 cram 14.6 GB
EGAF50000330394 crai 1.1 MB
EGAF50000330395 cram 220.7 MB
EGAF50000330396 crai 37.1 kB
EGAF50000330397 crai 40.2 kB
EGAF50000330398 cram 232.2 MB
EGAF50000330399 crai 53.5 kB
EGAF50000330400 cram 358.4 MB
EGAF50000330401 cram 302.4 MB
EGAF50000330402 crai 43.9 kB
EGAF50000330403 cram 296.4 MB
EGAF50000330404 crai 46.6 kB
EGAF50000330405 cram 208.7 MB
EGAF50000330406 crai 37.8 kB
EGAF50000330407 cram 30.9 GB
EGAF50000330408 crai 2.3 MB
EGAF50000330409 cram 281.2 MB
EGAF50000330410 crai 44.0 kB
EGAF50000330411 cram 307.3 MB
EGAF50000330412 crai 47.2 kB
EGAF50000330413 crai 40.7 kB
EGAF50000330414 cram 253.6 MB
EGAF50000330415 cram 346.0 MB
EGAF50000330416 crai 51.1 kB
EGAF50000330417 cram 277.5 MB
EGAF50000330418 crai 41.6 kB
EGAF50000330419 cram 3.3 GB
EGAF50000330420 crai 337.6 kB
EGAF50000330421 cram 290.0 MB
EGAF50000330422 crai 42.1 kB
EGAF50000330423 cram 103.7 kB
EGAF50000330424 crai 297 Bytes
EGAF50000330425 cram 248.0 MB
EGAF50000330426 crai 40.7 kB
EGAF50000330427 cram 16.8 GB
EGAF50000330428 crai 1.1 MB
EGAF50000330429 cram 248.9 MB
EGAF50000330430 crai 38.5 kB
EGAF50000330431 cram 291.5 MB
EGAF50000330432 crai 44.3 kB
EGAF50000330433 cram 282.5 MB
EGAF50000330434 crai 44.2 kB
EGAF50000330435 cram 366.8 MB
EGAF50000330436 crai 53.5 kB
EGAF50000330437 cram 209.1 MB
EGAF50000330438 crai 37.4 kB
EGAF50000330439 cram 20.5 GB
EGAF50000330440 crai 1.5 MB
EGAF50000330441 cram 220.3 MB
EGAF50000330442 crai 38.1 kB
EGAF50000330443 cram 308.9 MB
EGAF50000330444 crai 48.1 kB
EGAF50000330445 cram 308.6 MB
EGAF50000330446 crai 48.1 kB
EGAF50000330447 cram 235.1 MB
EGAF50000330448 crai 38.8 kB
EGAF50000330449 cram 299.9 MB
EGAF50000330450 crai 47.1 kB
EGAF50000330451 cram 308.5 MB
EGAF50000330452 crai 45.5 kB
EGAF50000330453 cram 292.2 MB
EGAF50000330454 crai 45.2 kB
EGAF50000330455 cram 618.7 MB
EGAF50000330456 crai 73.8 kB
EGAF50000330457 crai 39.9 kB
EGAF50000330458 cram 240.3 MB
EGAF50000330459 crai 653.9 kB
EGAF50000330460 cram 8.6 GB
EGAF50000330461 cram 19.1 GB
EGAF50000330462 crai 1.4 MB
EGAF50000330463 cram 14.0 GB
EGAF50000330464 crai 1.0 MB
EGAF50000330465 cram 328.8 MB
EGAF50000330466 crai 48.3 kB
EGAF50000330467 cram 289.4 MB
EGAF50000330468 crai 44.6 kB
EGAF50000330469 cram 262.8 MB
EGAF50000330470 crai 41.8 kB
EGAF50000330471 cram 274.2 MB
EGAF50000330472 crai 44.0 kB
EGAF50000330473 cram 325.2 MB
EGAF50000330474 crai 46.0 kB
EGAF50000330475 cram 270.1 MB
EGAF50000330476 crai 42.8 kB
EGAF50000330477 crai 672.7 kB
EGAF50000330478 cram 32.7 GB
EGAF50000330479 crai 584.8 kB
EGAF50000330480 cram 13.4 GB
EGAF50000330481 crai 512.0 kB
EGAF50000330482 cram 12.4 GB
EGAF50000330483 cram 13.2 GB
EGAF50000330484 crai 532.0 kB
EGAF50000330485 cram 66.1 GB
EGAF50000330486 crai 2.8 MB
EGAF50000330487 cram 15.4 GB
EGAF50000330488 crai 599.8 kB
EGAF50000330489 cram 6.9 GB
EGAF50000330490 crai 370.7 kB
EGAF50000330491 cram 6.5 GB
EGAF50000330492 crai 271.3 kB
EGAF50000330493 cram 38.9 GB
EGAF50000330494 crai 788.5 kB
EGAF50000330495 crai 2.3 MB
EGAF50000330496 cram 30.9 GB
192 Files (3.6 TB)