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Longitudinal single-cell transcriptomic study in patient-derived xenografts of pediatric T-ALL

In this study, we conducted single cell full length total RNA sequencing (VASA-seq) on 13 matched pediatric T-ALL PDX samples at initial diagnosis and relapse, along with 5 non-relapsing PDX samples collected at initial diagnosis. We identified a subpopulation of T-ALL cells with stem-like cell features that expands substantially at relapse indicating resistance to first-line therapy. Chemotherapy resistance was further validated through functional testing: Two samples were subjected to in-vitro drug testing, treated with Cytarabine for three days, followed by single-cell transcriptomic analysis using 10x Genomics. Additionally, in-vivo drug testing was conducted on one sample, involving re-engraftment into mice and treatment with a combination of Vincristine, Doxorubicin, and Dexamethasone. Single-cell transcriptomic analysis using 10x Genomics was performed after 0, 15 and 30 days of treatment.

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Controlled data use for health/medical/biomedical purposes.

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 T-ALL research group at the University Hospital Heidelberg 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: T-ALL research group at the University Hospital Heidelberg 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. 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 T-ALL research group at the University Hospital Heidelberg, within 30 days of any changes or departures of Authorised Personnel. 13. The User Institution will notify T-ALL research group at the University Hospital Heidelberg, prior to any significant changes to the protocol for the Project. 14. The User Institution will notify T-ALL research group at the University Hospital Heidelberg, as soon as it becomes aware of a breach of the terms or conditions of this agreement. 15. T-ALL research group at the University Hospital Heidelberg 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 T-ALL research group at the University Hospital Heidelberg. 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. Agreed for User Institution Signature: Name: Title: Date: Principal Investigator I confirm that I have read and understood this Agreement. Signature: Name: Title: Date: Agreed for XXXXX 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) 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 T-ALL research group at the University Hospital Heidelberg, 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. T-ALL research group at the University Hospital Heidelberg, 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 XX months after these data were first made available on the relevant hosting database, unless T-ALL research group at the University Hospital Heidelberg, 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 (EGAS00001003248), and acknowledge its use in a form agreed by the User Institution with T-ALL research group at the University Hospital Heidelberg.

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
EGAS50000000582 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 Located in
EGAF50000193785 fastq.gz 1.4 GB
EGAF50000193786 fastq.gz 3.1 GB
EGAF50000193787 fastq.gz 1.6 GB
EGAF50000193788 fastq.gz 3.5 GB
EGAF50000193789 fastq.gz 1.3 GB
EGAF50000193790 fastq.gz 2.9 GB
EGAF50000193791 fastq.gz 1.4 GB
EGAF50000193792 fastq.gz 3.1 GB
EGAF50000193793 fastq.gz 2.8 GB
EGAF50000193794 fastq.gz 5.1 GB
EGAF50000193795 fastq.gz 1.1 GB
EGAF50000193796 fastq.gz 1.9 GB
EGAF50000193797 fastq.gz 2.2 GB
EGAF50000193798 fastq.gz 4.2 GB
EGAF50000193799 fastq.gz 2.5 GB
EGAF50000193800 fastq.gz 4.2 GB
EGAF50000193801 fastq.gz 985.5 MB
EGAF50000193802 fastq.gz 2.1 GB
EGAF50000193803 fastq.gz 1.0 GB
EGAF50000193804 fastq.gz 2.3 GB
EGAF50000193805 fastq.gz 1.3 GB
EGAF50000193806 fastq.gz 2.8 GB
EGAF50000193807 fastq.gz 1.5 GB
EGAF50000193808 fastq.gz 3.2 GB
EGAF50000193809 fastq.gz 3.3 GB
EGAF50000193810 fastq.gz 5.9 GB
EGAF50000193811 fastq.gz 3.4 GB
EGAF50000193812 fastq.gz 6.4 GB
EGAF50000193813 fastq.gz 2.4 GB
EGAF50000193814 fastq.gz 4.6 GB
EGAF50000193815 fastq.gz 1.5 GB
EGAF50000193816 fastq.gz 2.8 GB
EGAF50000193817 fastq.gz 1.8 GB
EGAF50000193818 fastq.gz 3.4 GB
EGAF50000193819 fastq.gz 1.5 GB
EGAF50000193820 fastq.gz 2.7 GB
EGAF50000193821 fastq.gz 1.7 GB
EGAF50000193822 fastq.gz 3.2 GB
EGAF50000193823 fastq.gz 1.0 GB
EGAF50000193824 fastq.gz 1.9 GB
EGAF50000193825 fastq.gz 1.3 GB
EGAF50000193826 fastq.gz 2.8 GB
EGAF50000193827 fastq.gz 1.1 GB
EGAF50000193828 fastq.gz 2.3 GB
EGAF50000193829 fastq.gz 1.1 GB
EGAF50000193830 fastq.gz 2.5 GB
EGAF50000193831 fastq.gz 969.1 MB
EGAF50000193832 fastq.gz 2.0 GB
EGAF50000193833 fastq.gz 1.0 GB
EGAF50000193834 fastq.gz 1.9 GB
EGAF50000193835 fastq.gz 1.3 GB
EGAF50000193836 fastq.gz 2.5 GB
EGAF50000193837 fastq.gz 1.5 GB
EGAF50000193838 fastq.gz 2.6 GB
EGAF50000193839 fastq.gz 1.4 GB
EGAF50000193840 fastq.gz 2.7 GB
EGAF50000193841 fastq.gz 1.5 GB
EGAF50000193842 fastq.gz 3.2 GB
EGAF50000193843 fastq.gz 1.8 GB
EGAF50000193844 fastq.gz 3.8 GB
EGAF50000193845 fastq.gz 3.2 GB
EGAF50000193846 fastq.gz 6.1 GB
EGAF50000193847 fastq.gz 1.6 GB
EGAF50000193848 fastq.gz 3.0 GB
EGAF50000193849 fastq.gz 2.9 GB
EGAF50000193850 fastq.gz 1.9 GB
EGAF50000193851 fastq.gz 5.4 GB
EGAF50000193852 fastq.gz 1.3 GB
EGAF50000193853 fastq.gz 3.6 GB
EGAF50000193854 fastq.gz 2.6 GB
EGAF50000193855 fastq.gz 1.2 GB
EGAF50000193856 fastq.gz 2.5 GB
EGAF50000193857 fastq.gz 1.4 GB
EGAF50000193858 fastq.gz 3.2 GB
EGAF50000193859 fastq.gz 3.0 GB
EGAF50000193860 fastq.gz 1.3 GB
EGAF50000193861 fastq.gz 3.0 GB
EGAF50000193862 fastq.gz 5.5 GB
EGAF50000193863 fastq.gz 1.8 GB
EGAF50000193864 fastq.gz 3.4 GB
EGAF50000193865 fastq.gz 3.4 GB
EGAF50000193866 fastq.gz 1.9 GB
EGAF50000193867 fastq.gz 1.3 GB
EGAF50000193868 fastq.gz 2.2 GB
EGAF50000193869 fastq.gz 3.3 GB
EGAF50000193870 fastq.gz 1.5 GB
EGAF50000193871 fastq.gz 1.6 GB
EGAF50000193872 fastq.gz 3.4 GB
EGAF50000193873 fastq.gz 2.3 GB
EGAF50000193874 fastq.gz 4.7 GB
EGAF50000193875 fastq.gz 1.2 GB
EGAF50000193876 fastq.gz 2.7 GB
EGAF50000193877 fastq.gz 2.8 GB
EGAF50000193878 fastq.gz 1.3 GB
EGAF50000193879 fastq.gz 1.4 GB
EGAF50000193880 fastq.gz 3.0 GB
EGAF50000193881 fastq.gz 1.1 GB
EGAF50000193882 fastq.gz 2.3 GB
EGAF50000193883 fastq.gz 1.2 GB
EGAF50000193884 fastq.gz 2.6 GB
EGAF50000193885 fastq.gz 2.9 GB
EGAF50000193886 fastq.gz 1.5 GB
EGAF50000193887 fastq.gz 1.4 GB
EGAF50000193888 fastq.gz 2.6 GB
EGAF50000193889 fastq.gz 3.0 GB
EGAF50000193890 fastq.gz 1.5 GB
EGAF50000193891 fastq.gz 3.6 GB
EGAF50000193892 fastq.gz 2.0 GB
EGAF50000193893 fastq.gz 1.7 GB
EGAF50000193894 fastq.gz 3.7 GB
EGAF50000193895 fastq.gz 1.4 GB
EGAF50000193896 fastq.gz 3.2 GB
EGAF50000193897 fastq.gz 1.6 GB
EGAF50000193898 fastq.gz 3.5 GB
EGAF50000193899 fastq.gz 2.8 GB
EGAF50000193900 fastq.gz 1.2 GB
EGAF50000193901 fastq.gz 1.5 GB
EGAF50000193902 fastq.gz 2.8 GB
EGAF50000193903 fastq.gz 2.3 GB
EGAF50000193904 fastq.gz 4.2 GB
EGAF50000193905 fastq.gz 1.1 GB
EGAF50000193906 fastq.gz 1.5 GB
EGAF50000193907 fastq.gz 2.1 GB
EGAF50000193908 fastq.gz 2.9 GB
EGAF50000193909 tar.gz 121.7 MB
EGAF50000193910 tar.gz 139.1 MB
EGAF50000193911 tar.gz 22.8 MB
EGAF50000193912 tar.gz 19.5 MB
EGAF50000193913 tar.gz 19.8 MB
EGAF50000193914 tar.gz 110.8 MB
EGAF50000193915 tar.gz 102.7 MB
131 Files (304.0 GB)