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RNA-seq as a tool for evaluating human embryo competence

The majority of embryos that are created through IVF do not implant. It seems plausible that rates of implantation would improve if we had a better understanding of molecular factors affecting embryo competence. Currently, the process of selecting an embryo for uterine transfer utilizes an ad-hoc combination of morphological criteria, the kinetics of development, and genetic testing for aneuploidy. However, no single criterion can ensure selection of a viable embryo. In contrast, RNA-sequencing of embryos could yield highly dimensional data, which may provide additional insight and illuminate the discrepancies among current selection criteria. Indeed, recent advances enabling the production of RNA-sequencing (RNA-seq) libraries from single cells have facilitated the application of this technique to the study of some transcriptional events in early human development. However, these studies have not assessed the quality of their constituent embryos relative to commonly used embryological criteria. Here, we perform proof-of-principle advancement to clinical selection procedures by generating high quality RNA-seq libraries from a trophectoderm biopsy as well as the remaining whole embryo. We combine state-of-the-art embryological methods with low-input RNA-seq to develop the first transcriptome-wide approach for use in future predictive embryology studies. Specifically, we demonstrate the capacity of RNA-seq as a promising tool in preimplantation screening by showing that biopsies of an embryo can capture valuable information content available in the whole embryo from which they are derived. Furthermore, we show that this technique can be used to generate a RNA-based digital karyotype, and to identify candidate competence-associated genes. Together, these data establish the foundation for a future RNA-based diagnostic in IVF.

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Data access agreement for human embryo RNA-sequencing data

DATA ACCESS AGREEMENT (the “Agreement”) between President and Fellows of Harvard College, acting on behalf of the Harvard Department of Stem Cell and Regenerative Biology, hereinafter referred to as “Harvard” and the European Genome-phenome Archive (EGA), hereinafter referred to as “User Institution.” Harvard and User Institution may hereinafter be referred to individually as a “Party,” and collectively as the “Parties.” The effective date of this Agreement shall be the final date of execution (the “Effective Date”). WHEREAS, Harvard shall make Data, as defined below, available to User Institution as described herein. WHEREAS, the Data is being hosted by the European Genome-phenome Archive (“EGA”) and access is controlled and provided by Harvard. WHEREAS, the research contemplated by this Agreement will further the instructional and research objectives of Harvard in a manner consistent with its status as a non-profit, tax-exempt, educational institution. NOW, THEREFORE, the Parties hereto agree as follows: 1. PROJECT. Harvard shall provide the Data to User Institution for the purpose set forth in Exhibit A (the “Project”). The User Institution will notify Harvard thirty (30) days prior to any significant changes to the Project. The Data are provided at no cost. The Data shall not be used except as authorized under this Agreement. 2. USER INSTITUTION RESEARCHER. For purposes of this Agreement, a “User Institution Researcher” is an individual researcher who (i) is a faculty member, fellow, student, or employee of User Institution, (ii) needs to access the Data for the Project, and (iii) is listed in Exhibit A. The Data will be made available only to User Institution Researchers. The Data shall not be further distributed to others, including without limitation, employees or representatives of User Institution other than the User Institution Researchers, without Harvard’s prior written consent. The User Institution will notify Harvard within thirty (30) days of any changes or departures of User Institution Researchers, and Harvard may unilaterally amend Exhibit A to reflect such change or departure. 3. DATA. “Data” means the confidential and proprietary information that is described in Exhibit B, to be disclosed by Harvard for the Project to the User Institution Researchers. 4. TERM. The Term commences on the Effective Date and shall continue as long as the User Institution Researcher holds a valid EGA account, unless terminated earlier under Section 11. 5. LICENSE TO USE DATA. Subject to the terms and conditions of this Agreement and any terms of access set out by the EGA, Harvard hereby grants to User Institution and User Institution Researchers the non-exclusive rights (i) to use the Data as described in Exhibit A of this Agreement; and (ii) subject to Section 7, to publish, reproduce or use the research results and other products of the research in works such as (without limitation) academic journals, books, online publications, unpublished working papers, and reports, materials and information included in presentations for academic seminars and conferences and similar events. Under no circumstances shall the Data be used in connection with the diagnosis or treatment of human subjects. Data may be used in the form of raw data and aggregated form, however, User Institution may not publish the raw sequencing Data. Data may be combined with other data sets, except as set forth below. Nothing in this Agreement will be construed to confer on User Institution any ownership interest, license or other rights as to the Data or any other intellectual property of Harvard, except as expressly stated in this Agreement. 6. INTELLECTUAL PROPERTY. User Institution or User Institution Researchers, as the case may be, shall own the entire right, title and interest, including all patents, copyrights, and other intellectual property rights, in and to (i) all their research results based on, derived from or using the Data, and (ii) all tangible materials, inventions, discoveries, works of authorship, software, information, and data conceived or developed by them in the performance of the Project. The User Institution agrees not to make intellectual property claims on the Data themselves 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. 7. PUBLICATION. User Institution and User Institution Researchers will be free to publish the results of the research derived from, based on or using the Data after providing Harvard in advance with a thirty (30) day period in which to review each proposed publication in confidence, provided that the scope and purpose of such review will be limited to the identification of personally identifiable or confidential information contained in the publication. At the end of the 30-day review period, User Institution and User Institution Researchers will have the right to publish. For the avoidance of doubt, once a work has been reviewed, the content may be disclosed in substantially the same form on multiple occasions without additional review by Harvard. User Institution agrees to recognize the contribution of Harvard in all written or oral public disclosures concerning User Institution’s research using the Data, by either acknowledgment or co-authorship, as appropriate in accordance with scholarly standards. In any publications based on these Data, the User Institution shall 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 and Harvard. The User Institution agrees to follow the Fort Lauderdale Guidelines (https://wellcome.ac.uk/sites/default/files/wtd003207_0.pdf) and the Toronto Statement (http://www.nature.com/nature/journal/v461/n7261/full/461168a.html). 8. CONFIDENTIALITY. User Institution (i) will use reasonable care to protect the security of Data, (ii) will limit access to Data to authorized recipients as provided in Section 1; and (iii) will not at any time during or after the term of this Agreement disclose Data to any other person without first obtaining Harvard’s prior written consent (except as otherwise required by law in which case User Institution shall, unless otherwise prohibited by law, notify Harvard prior to such disclosure). User Institution will report promptly to Harvard any disclosure of Data not provided for by this Agreement of which it becomes aware. a. Confidentiality of Research Participants. User Institution 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 Exhibit B to protect these Data. The User Institution agrees to protect the confidentiality of research participants in any research papers or publications that User Institution Researchers prepare by taking all reasonable care to limit the possibility of identification. 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. The User Institution agrees only to transfer or disclose these Data, in whole or part, or any material derived from these Data, to the User Institution Researchers listed in Exhibit A. 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. 9. NO REPRESENTATIONS AND WARRANTIES. ALL DATA ARE PROVIDED “AS IS.” HARVARD MAKES NO REPRESENTATIONS OR WARRANTIES, EXPRESS OR IMPLIED, REGARDING THE DATA’S ACCURACY, COMPLETENESS, OR USE. THERE ARE NO EXPRESS OR IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR THAT THE USE OF THE DATA WILL NOT INFRINGE ANY PATENT, COPYRIGHT, TRADEMARK, OR OTHER PROPRIETARY RIGHTS OR OTHER RIGHTS OF ANY THIRD PARTY. 10. USE OF NAMES. Except as expressly provided in this Agreement, neither Party shall use or register the other Party’s name (alone or as part of another name) or any logos, seals, insignia or other words, names, symbols or devices that identify the other party, including any school, unit, division or affiliate (“Names”) for any marketing, publicity, or promotional purpose in connection with this Agreement or the Project except with the prior written approval of, and in accordance with restrictions required by, the Party whose name who is to be used. The foregoing notwithstanding, the Parties agree that each Party may respond to legitimate business inquiries with factual information regarding the existence and purpose of the relationship that is the subject of this Agreement, without written permission from the other Party. In any such statements, the relationship of the Parties shall be accurately and appropriately described. 11. TERMINATION. Harvard may terminate this Agreement for any reason by providing thirty (30) days’ prior written notice to the User Institution. Harvard may terminate this Agreement immediately if the User Institution is determined to be in breach of this Agreement. Upon the earliest to occur - either termination or expiration of this Agreement – User Institution and all User Institution Researchers will destroy any Data held, including all copies and backup copies, within a reasonable time limit, but not more than thirty (30) days from the date of termination or expiration of this Agreement, provided, however, that User Institution may retain one copy of the Data to the extent necessary to comply with the records retention requirements under any law or regulation and for the purposes of research integrity and verification. 12. LIMITATION OF LIABILITY. HARVARD, AND ALL OTHER PARTIES INVOLVED IN THE CREATION, FUNDING OR PROTECTION OF THE DATA (I) EXCLUDE TO THE FULLEST EXTENT PERMITTED BY LAW ALL LIABILITY FOR ACTIONS, CLAIMS, PROCEEDINGS, DEMANDS, LOSSES (INCLUDING LOST REVENUES OR PROFITS), COSTS, AWARDS, DAMAGES AND PAYMENTS THAT MAY ARISE (WHETHER DIRECTLY OR INDIRECTLY, AND WHETHER FROM BREACH OF THIS AGREEMENT, NEGLIGENCE, STRICT LIABILITY OR OTHER TORT, OR ANY OTHER CAUSE) IN ANY WAY WHATSOEVER FROM THIS AGREEMENT, RECIPIENT’S USE OF THE DATA, OR THE UNAVAILABILITY OF, OR BREAK IN ACCESS TO, THE DATA FOR WHATEVER REASON; AND (II) BEAR NO RESPONSIBILITY FOR THE FURTHER ANALYSIS OR INTERPRETATION OF THE DATA. User Institution assumes all liability for claims by third parties which may arise from its use, storage or disposal of the Data. 13. GOVERNING LAW. This Agreement shall be governed by and interpreted in accordance with the laws of the Commonwealth of Massachusetts (excluding conflicts of laws rules) and shall be subject to the exclusive jurisdiction of the state and federal courts sitting in the Commonwealth of Massachusetts. 14. COMPLIANCE WITH LAW. User Institution will perform under this Agreement in compliance with all requirements of all applicable laws, rules and regulations, as well as all professional standards applicable to such research. 15. INSPECTION. If requested, the User Institution will allow data security and management documentation to be inspected by Harvard to verify that it is complying with the terms of this Agreement. 16. NOTICES. Any notice under this Agreement, excluding the actual provision of Data, may be delivered in person, or sent by fax (with the original sent promptly by ordinary mail), by electronic mail, by registered or certified mail, postage prepaid, or by recognized delivery service, to the appropriate addresses listed in Exhibit C or to the most recent other contact information provided by the recipient (by means of notice complying with this paragraph), and such notice shall be deemed to have been given when so delivered, sent by fax or electronic mail, or mailed. 17. INDEPENDENT CONTRACTOR. The Parties are independent contractors and neither Party shall be deemed to be an agent or employee of the other Party. Neither Party shall have authority to make any statements, representations or commitments of any kind on behalf of the other Party, or to take any action which shall be binding on the other Party. 18. ASSIGNMENT. This Agreement and all rights and obligations hereunder shall not be assigned (whether through merger or consolidation, by operation of law, or otherwise), without the written consent of the other Party and any attempt to assign without such consent shall be void. 19. MODIFICATION. The User Institution accepts that it may be necessary for Harvard to alter the terms of this Agreement from time to time. In the event that changes are required, Harvard shall notify the User Institution to inform it of the changes and the User Institution may elect to accept the changes (in which case the Parties shall execute a written amendment to this Agreement reflecting such changes) or terminate this Agreement. Except as provided in Section 2 or in this Section 19, no modification or waiver of any provision of this Agreement or any Exhibit shall be valid unless in writing and executed by duly-authorized representatives of both Parties. A failure by one of the Parties to this Agreement to assert its rights hereunder shall not be deemed a waiver of such rights. No such failure or waiver in writing by any one of the Parties hereto with respect to any rights shall extend to or affect any subsequent breach or impair any right consequent thereon. 20. SEVERABILITY. If any provision of this Agreement is or becomes invalid or is ruled invalid by any court of competent jurisdiction or is deemed unenforceable, it is the intention of the parties that the remainder of this Agreement shall not be affected. 21. COUNTERPARTS. This Agreement may be executed in two or more counterparts, and by facsimile or electronic transmission, each of which will be deemed to be an original, but all of which together shall constitute one and the same instrument. 22. ENTIRE AGREEMENT. Unless otherwise specified, this Agreement and its Exhibits embody the entire understanding between User Institution and Harvard, and any prior or contemporaneous representations, either oral or written, are hereby superseded.

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
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
EGAF00002465986 fastq.gz 442.4 MB
EGAF00002465987 fastq.gz 462.9 MB
EGAF00002465988 fastq.gz 416.4 MB
EGAF00002465989 fastq.gz 439.7 MB
EGAF00002465990 fastq.gz 920.3 MB
EGAF00002465991 fastq.gz 922.7 MB
EGAF00002465992 fastq.gz 711.3 MB
EGAF00002465993 fastq.gz 786.7 MB
EGAF00002465994 fastq.gz 409.4 MB
EGAF00002465995 fastq.gz 403.9 MB
EGAF00002465996 fastq.gz 523.0 MB
EGAF00002465997 fastq.gz 529.0 MB
EGAF00002465998 fastq.gz 877.2 MB
EGAF00002465999 fastq.gz 958.8 MB
EGAF00002466000 fastq.gz 185.7 MB
EGAF00002466001 fastq.gz 197.0 MB
EGAF00002466002 fastq.gz 635.2 MB
EGAF00002466003 fastq.gz 655.9 MB
EGAF00002466004 fastq.gz 653.1 MB
EGAF00002466005 fastq.gz 659.8 MB
EGAF00002466006 fastq.gz 1.3 GB
EGAF00002466007 fastq.gz 1.3 GB
EGAF00002466008 fastq.gz 737.9 MB
EGAF00002466009 fastq.gz 743.3 MB
EGAF00002466010 fastq.gz 1.2 GB
EGAF00002466011 fastq.gz 1.3 GB
EGAF00002466012 fastq.gz 954.6 MB
EGAF00002466013 fastq.gz 966.0 MB
EGAF00002466014 fastq.gz 869.2 MB
EGAF00002466015 fastq.gz 891.2 MB
EGAF00002466016 fastq.gz 881.0 MB
EGAF00002466017 fastq.gz 905.5 MB
EGAF00002466018 fastq.gz 354.2 MB
EGAF00002466019 fastq.gz 390.7 MB
EGAF00002466020 fastq.gz 296.1 MB
EGAF00002466021 fastq.gz 298.2 MB
EGAF00002466022 fastq.gz 398.8 MB
EGAF00002466023 fastq.gz 407.3 MB
EGAF00002466024 fastq.gz 316.9 MB
EGAF00002466025 fastq.gz 330.7 MB
EGAF00002466026 fastq.gz 453.6 MB
EGAF00002466027 fastq.gz 472.7 MB
EGAF00002466028 fastq.gz 375.4 MB
EGAF00002466029 fastq.gz 368.8 MB
EGAF00002466030 fastq.gz 524.3 MB
EGAF00002466031 fastq.gz 525.8 MB
EGAF00002466032 fastq.gz 753.3 MB
EGAF00002466033 fastq.gz 745.3 MB
EGAF00002466034 fastq.gz 737.9 MB
EGAF00002466035 fastq.gz 732.6 MB
EGAF00002466036 fastq.gz 1.5 GB
EGAF00002466037 fastq.gz 1.7 GB
EGAF00002466038 fastq.gz 642.2 MB
EGAF00002466039 fastq.gz 623.4 MB
EGAF00002466040 fastq.gz 637.1 MB
EGAF00002466041 fastq.gz 677.5 MB
EGAF00002466042 fastq.gz 880.2 MB
EGAF00002466043 fastq.gz 846.7 MB
EGAF00002466044 fastq.gz 716.1 MB
EGAF00002466045 fastq.gz 784.9 MB
EGAF00002466046 fastq.gz 822.2 MB
EGAF00002466047 fastq.gz 160.5 MB
EGAF00002466048 fastq.gz 847.8 MB
EGAF00002466049 fastq.gz 840.9 MB
EGAF00002466050 fastq.gz 735.6 MB
EGAF00002466051 fastq.gz 737.4 MB
EGAF00002466052 fastq.gz 1.2 GB
EGAF00002466053 fastq.gz 1.2 GB
EGAF00002466054 fastq.gz 848.4 MB
EGAF00002466055 fastq.gz 861.2 MB
EGAF00002466056 fastq.gz 928.5 MB
EGAF00002466057 fastq.gz 938.5 MB
EGAF00002466058 fastq.gz 932.1 MB
EGAF00002466059 fastq.gz 1.0 GB
EGAF00002466060 fastq.gz 947.8 MB
EGAF00002466061 fastq.gz 1.0 GB
EGAF00002466062 fastq.gz 1.0 GB
EGAF00002466063 fastq.gz 1.1 GB
EGAF00002466064 fastq.gz 781.7 MB
EGAF00002466065 fastq.gz 808.7 MB
EGAF00002466066 fastq.gz 718.1 MB
EGAF00002466067 fastq.gz 714.6 MB
EGAF00002466068 fastq.gz 691.7 MB
EGAF00002466069 fastq.gz 703.4 MB
EGAF00002466070 fastq.gz 817.3 MB
EGAF00002466071 fastq.gz 818.3 MB
EGAF00002466072 fastq.gz 842.5 MB
EGAF00002466073 fastq.gz 844.0 MB
EGAF00002466074 fastq.gz 949.3 MB
EGAF00002466075 fastq.gz 960.5 MB
EGAF00002466076 fastq.gz 920.4 MB
EGAF00002466077 fastq.gz 945.7 MB
EGAF00002466078 fastq.gz 785.6 MB
EGAF00002466079 fastq.gz 799.1 MB
EGAF00002466080 fastq.gz 957.2 MB
EGAF00002466081 fastq.gz 974.4 MB
EGAF00002466082 fastq.gz 859.8 MB
EGAF00002466083 fastq.gz 857.3 MB
EGAF00002466084 fastq.gz 547.6 MB
EGAF00002466085 fastq.gz 545.6 MB
EGAF00002466086 fastq.gz 938.6 MB
EGAF00002466087 fastq.gz 957.7 MB
EGAF00002466088 fastq.gz 611.2 MB
EGAF00002466089 fastq.gz 637.1 MB
EGAF00002466090 fastq.gz 667.6 MB
EGAF00002466091 fastq.gz 681.6 MB
EGAF00002466092 fastq.gz 140.5 MB
EGAF00002466093 fastq.gz 143.0 MB
108 Files (80.0 GB)