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ctDNA monitoring using patient-specific sequencing and integration of variant reads - Breast cohort

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to individual parts per million. This resulted in median Area Under the Curve (AUC) values of 0.98 in advanced cancers, and 0.80 in early stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that the INVAR may be applied without requiring personalized sequencing panels, so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.

Request Access

Policy for access to data included in the following publication; ctDNA monitoring using patient-specific sequencing and integration of variant reads

~~~ Definitions: Confidential Information: means any information provided by the Data Provider relating to the Data Data: The managed access dataset(s) to which the User Institution has requested access, as detailed in Schedule B. Data Provider: THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE of The Old Schools, Trinity Lane, Cambridge CB2 1TN, United Kingdom and the Cambridge University Hospitals NHS Foundation Trust of Addenbrooke’s Hospital, Cambridge, CB2 0QQ; represented by staff of the Rosenfeld Group at the Cancer Research UK Cambridge Institute, and contactable by email at Rosenfeld.LabAdmin@cruk.cam.ac.uk or future email as updated; or future representatives as indicated in Data Access Committee(s) for the dataset(s) defined in Schedule B. Data Subject: means an individual who participated in research studies from whom the Data was derived. External Collaborator: A collaborator of the User, working for an institution other than the User Institution. Personal Data: means information and/or data about one or more living person who is the subject of personal data and who can be identified from that information, as provided under the General Data Protection Regulation (EU) 2016/679 (as amended from time to time), including but not limited to surname, initials, date of birth, address and postcodes, national insurance number, hospital number or NHS number. Project: The research project for which the User Institution has requested access to these Data, as defined in Schedule B. Publications: Includes, without limitation, articles published in print journals, electronic journals, reviews, books, posters and other written and verbal presentations of research. User: The principal investigator for the Project. User Institution(s): The Institution that has requested access to the Data. User Institution is referred to within this Agreement as “You” (and “Your” shall be construed accordingly). Data Provider will provide access to Data to the User Institution under the following Terms and Conditions: 1. You agree to preserve, at all times, the confidentiality and privacy of information and Data pertaining to Data Subjects. In particular, you undertake not to use, or attempt to use the Data to compromise or otherwise breach or infringe the confidentiality and privacy of information on Data Subjects. You agree to protect the confidentiality of Data Subjects in any Publications that you prepare by taking all reasonable care to limit the possibility of identification. You agree not to attempt to link Data to any other data source on the same samples, link the Data to any person or otherwise identify any Data Subject from the Data. 2. You agree not to transfer or disclose the Data, in whole or part, to others, except to persons within the User Institution for carrying out the Project or as reasonably necessary for Data/safety monitoring or programme management. If You wish to disclose the Data to a collaborator outside the User Institution, the third party must make a separate application for access to the Data. 3. You agree to use the Data for the advancement of medical research, and solely for the approved purpose and Project described in Schedule B and for no other purpose. 4. You agree that Data may be reissued from time to time, with suitable versioning. If the reissue is at the request of Data Subjects and/or other ethical scrutiny or concerns, you will destroy earlier versions of the Data, and upon request of Data Provider, provide written certification of such destruction. Your obligations as set out in this form pertaining to the Data and its use will continue to operate in full force and effect after Data is destroyed. 5. You agree to acknowledge in any Publication based in whole or part on the Data, the published paper(s) from which the Data derives, and the version of the Data. 6. You agree and acknowledge that the researchers of this study, the original Data creators, depositors, or copyright holders, and the Data Provider: a) bear no legal responsibility or liability for the accuracy or comprehensiveness of the Data, or from any use of the Data including further analysis or interpretation of such Data; and b) shall have no liability for any direct or indirect, consequential, or incidental damages or losses whatsoever arising out of Your use of the Data, or from the unavailability of, or lack of access to, the Data for whatever reason; and c) disclaim any and all representations, conditions or warranties (either express, implied or statutory) regarding the Data, including accuracy of the Data or that the Data corresponds with a particular description or is fit for a particular purpose. 7. You understand and acknowledge that the Data is owned by Data Provider and its collaborators and is protected by copyright, database rights and other intellectual property rights. You agree that you shall not reproduce or copy the Data, except as reasonably required to carry out the Project and for no other purpose, or sell all or any part of the Data in any circumstances. 8. You recognise that by granting You access to Data, no rights or ownership or intellectual property rights in or relating to the Data are transferred to You. 9. Upon any breach by You of the terms set out in this form, You will be required to destroy the Data in Your possession, and upon request, provide written certification to the Data Provider of such destruction. Your obligations as set out in this form pertaining to the Data and its use will continue to operate in full force and effect after Data is destroyed. 10. You accept that it may be necessary for the Data Provider to alter the terms of use of the Data from time to time. As an example, this may include specific provisions relating to the Data required by Data Provider or collaborator parties. In the event that changes are required, the Data Provider or their appointed agent will contact You to inform You of the changes and You may elect either to accept the changes or to destroy the Data in Your possession and cease its use. Your obligations as set out in this form pertaining to the Data and its use will continue to operate in full force and effect after Data is destroyed. 11. You agree that the Data is protected by and subject to applicable international laws. You are responsible for ensuring compliance with any such laws. The Data Provider reserves the right to request and inspect Your data security and management documentation to ensure the adequacy and compliance of data protection measures pertaining to storage and use of Data. 12. If the Data includes any identifiable Personal Data, You agree to: (a) take appropriate technical and organisational measures against the unauthorised or unlawful processing and/or use of the Data, any data derived from the Data and/or and all Confidential Information, against the accidental loss or destruction of, or damage to, such data and information. (b) ensure that the measures referred to in (a) shall include the measures set out in Schedule A. (c) restrict access to the Data, any data derived from the Data and all other Confidential Information to employees who strictly need access to such data and/or information to undertake the Project, and shall ensure that all such employees are reliable, and informed of the confidential nature of such data and/or information and the importance of processing it securely. (d) For the avoidance of doubt, You undertake not to disclose to a third party, whether in connection with the Project or otherwise, any data and/or information contained in or derived from the Data which constitutes Personal Data. Schedule A 1.1 You acknowledge and agree that the Data is pseudonymised Data and that You will become the Data Controller on receipt of such Data. 1.2 You will only process the Data for the purpose of carrying out the Project. 1.3 You agree that safeguards required under Article 89(1) of GDPR, and relevant conditions under the Data Protection Act 2018, are satisfied, and in particular that: (i) the processing of Data under or in connection with this Agreement is in the public interest; and (ii) if applicable, the Project has been subject to ethical review by an appropriate institutional review board or independent ethics committee. 1.4 The Data Provider does not intend to provide any information that may lead to You being able to identify any individual from whom any Data has been obtained. 1.5 You agree that You shall not analyse or make any use of any Data where it is reasonably foreseeable that such analysis or use may lead to the identification of any Data Subject or compromise the anonymity of any Data Subject in any way. 1.6 You shall notify the Data Provider immediately of any actual or suspected breach of security which involves the Data. Schedule B Name of the applicant and co-applicant(s), including affiliations, titles and contact details. For dataset deposited at EGA, applicants must have registered accounts at EGA. Student applicants must include their supervisors as a co-applicant. Name of registered user; Email; Job title; Supervisor*; Title of Project (in less than 30 words) Data Requested (please indicate relevant publication(s) describing the data, accession number(s) and/or relevant links to data, and [where relevant] details of and links to the respective Data Access Committee(s) (DAC)) Research Project: Please provide a clear description of the project and its specific aims in no more than 750 words. This should include specific details of what you plan to do with the data and include key references. Brief description of the infrastructure and experience for handling the requested data securely Signature of authorized signatory of User Institution Signature; Name; Title; Date; Signature of Principal Investigator I confirm that I have read and understood the TERMS AND CONDITIONS as set forth in this DATA ACCESS REQUEST FORM. Signature; Name; Title; Date; ~~~~~~~ Data Access Request Form, V1 CRUK-CI, Rosenfeld Lab, July 2019 ~~~

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
EGAS00001004446 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
EGAF00004173596 fq.gz 536.3 MB
EGAF00004173597 fq.gz 1.2 GB
EGAF00004173598 fq.gz 567.4 MB
EGAF00004173599 fq.gz 1.2 GB
EGAF00004173600 fq.gz 569.5 MB
EGAF00004173601 fq.gz 1.3 GB
EGAF00004173602 fq.gz 601.4 MB
EGAF00004173603 fq.gz 1.3 GB
EGAF00004173604 fq.gz 336.8 MB
EGAF00004173605 fq.gz 753.8 MB
EGAF00004173606 fq.gz 337.7 MB
EGAF00004173607 fq.gz 709.1 MB
EGAF00004173608 fq.gz 534.2 MB
EGAF00004173609 fq.gz 1.2 GB
EGAF00004173610 fq.gz 650.1 MB
EGAF00004173611 fq.gz 1.4 GB
EGAF00004173612 fq.gz 370.4 MB
EGAF00004173613 fq.gz 736.7 MB
EGAF00004173614 fq.gz 316.8 MB
EGAF00004173615 fq.gz 697.3 MB
EGAF00004173616 fq.gz 294.2 MB
EGAF00004173617 fq.gz 664.5 MB
EGAF00004173618 fq.gz 609.9 MB
EGAF00004173619 fq.gz 1.3 GB
EGAF00004173620 fq.gz 679.6 MB
EGAF00004173621 fq.gz 1.5 GB
EGAF00004173622 fq.gz 293.9 MB
EGAF00004173623 fq.gz 693.7 MB
EGAF00004173624 fq.gz 645.1 MB
EGAF00004173625 fq.gz 1.4 GB
EGAF00004173626 fq.gz 276.8 MB
EGAF00004173627 fq.gz 625.0 MB
EGAF00004173628 fq.gz 337.6 MB
EGAF00004173629 fq.gz 648.1 MB
EGAF00004173630 fq.gz 333.0 MB
EGAF00004173631 fq.gz 714.7 MB
EGAF00004173632 fq.gz 654.5 MB
EGAF00004173633 fq.gz 1.3 GB
EGAF00004173634 fq.gz 316.9 MB
EGAF00004173635 fq.gz 679.1 MB
EGAF00004173704 fq.gz 570.7 MB
EGAF00004173705 fq.gz 1.3 GB
EGAF00004173706 fq.gz 239.6 MB
EGAF00004173707 fq.gz 542.2 MB
EGAF00004173708 fq.gz 262.6 MB
EGAF00004173709 fq.gz 602.9 MB
EGAF00004173710 fq.gz 205.9 MB
EGAF00004173711 fq.gz 454.0 MB
EGAF00004173712 fq.gz 336.0 MB
EGAF00004173713 fq.gz 696.4 MB
EGAF00004173714 fq.gz 257.8 MB
EGAF00004173715 fq.gz 616.8 MB
EGAF00004173716 fq.gz 289.8 MB
EGAF00004173717 fq.gz 609.6 MB
EGAF00004173718 fq.gz 252.1 MB
EGAF00004173719 fq.gz 559.4 MB
EGAF00004173720 fq.gz 240.3 MB
EGAF00004173721 fq.gz 550.0 MB
EGAF00004173722 fq.gz 183.2 MB
EGAF00004173723 fq.gz 382.8 MB
EGAF00004173724 fq.gz 283.8 MB
EGAF00004173725 fq.gz 548.6 MB
EGAF00004173726 fq.gz 227.8 MB
EGAF00004173727 fq.gz 484.0 MB
EGAF00004173728 fq.gz 284.0 MB
EGAF00004173729 fq.gz 655.7 MB
EGAF00004173730 fq.gz 295.7 MB
EGAF00004173731 fq.gz 598.9 MB
EGAF00004173732 fq.gz 243.7 MB
EGAF00004173733 fq.gz 524.2 MB
EGAF00004173734 fq.gz 227.1 MB
EGAF00004173735 fq.gz 526.7 MB
EGAF00004173736 fq.gz 258.1 MB
EGAF00004173737 fq.gz 554.9 MB
EGAF00004173738 fq.gz 243.2 MB
EGAF00004173739 fq.gz 534.0 MB
EGAF00004173740 fq.gz 258.6 MB
EGAF00004173741 fq.gz 596.5 MB
EGAF00004173742 fq.gz 284.3 MB
EGAF00004173743 fq.gz 555.8 MB
EGAF00004174034 fq.gz 266.9 MB
EGAF00004174035 fq.gz 566.5 MB
EGAF00004174036 fq.gz 214.1 MB
EGAF00004174037 fq.gz 493.2 MB
EGAF00004174038 fq.gz 261.2 MB
EGAF00004174039 fq.gz 539.4 MB
EGAF00004174040 fq.gz 265.9 MB
EGAF00004174041 fq.gz 547.9 MB
EGAF00004174042 fq.gz 272.0 MB
EGAF00004174043 fq.gz 605.4 MB
EGAF00004174044 fq.gz 286.5 MB
EGAF00004174045 fq.gz 659.4 MB
EGAF00004174046 fq.gz 284.5 MB
EGAF00004174047 fq.gz 586.1 MB
EGAF00004174048 fq.gz 321.3 MB
EGAF00004174049 fq.gz 755.1 MB
EGAF00004174050 fq.gz 365.5 MB
EGAF00004174051 fq.gz 705.4 MB
EGAF00004174052 fq.gz 262.9 MB
EGAF00004174053 fq.gz 569.4 MB
EGAF00004174054 fq.gz 299.4 MB
EGAF00004174055 fq.gz 726.2 MB
EGAF00004174056 fq.gz 278.7 MB
EGAF00004174057 fq.gz 632.7 MB
EGAF00004174058 fq.gz 262.4 MB
EGAF00004174059 fq.gz 538.7 MB
EGAF00004174060 fq.gz 254.2 MB
EGAF00004174061 fq.gz 603.3 MB
EGAF00004174062 fq.gz 411.2 MB
EGAF00004174063 fq.gz 802.7 MB
EGAF00004174064 fq.gz 297.5 MB
EGAF00004174065 fq.gz 596.3 MB
EGAF00004174066 fq.gz 284.9 MB
EGAF00004174067 fq.gz 633.8 MB
EGAF00004174068 fq.gz 309.9 MB
EGAF00004174069 fq.gz 673.3 MB
EGAF00004174070 fq.gz 276.7 MB
EGAF00004174071 fq.gz 559.8 MB
EGAF00004174072 fq.gz 264.8 MB
EGAF00004174073 fq.gz 621.5 MB
EGAF00004174074 fq.gz 323.1 MB
EGAF00004174075 fq.gz 627.7 MB
EGAF00004174076 fq.gz 246.5 MB
EGAF00004174077 fq.gz 558.4 MB
EGAF00004174078 fq.gz 358.9 MB
EGAF00004174079 fq.gz 757.4 MB
EGAF00004174080 fq.gz 240.0 MB
EGAF00004174081 fq.gz 557.7 MB
EGAF00004174082 fq.gz 230.2 MB
EGAF00004174083 fq.gz 506.8 MB
EGAF00004176881 fq.gz 7.0 GB
EGAF00004176882 fq.gz 7.2 GB
EGAF00004176883 fq.gz 6.8 GB
EGAF00004176884 fq.gz 7.0 GB
EGAF00004176885 fq.gz 7.3 GB
EGAF00004176886 fq.gz 7.6 GB
EGAF00004176887 fq.gz 7.2 GB
EGAF00004176888 fq.gz 7.6 GB
EGAF00004176889 fq.gz 4.3 GB
EGAF00004176890 fq.gz 4.5 GB
EGAF00004176891 fq.gz 4.1 GB
EGAF00004176892 fq.gz 4.2 GB
EGAF00004176894 fq.gz 6.8 GB
EGAF00004176895 fq.gz 7.0 GB
EGAF00004176896 fq.gz 8.0 GB
EGAF00004176897 fq.gz 8.2 GB
EGAF00004176898 fq.gz 4.2 GB
EGAF00004176899 fq.gz 4.4 GB
EGAF00004176900 fq.gz 3.9 GB
EGAF00004176901 fq.gz 4.1 GB
EGAF00004176903 fq.gz 3.8 GB
EGAF00004176904 fq.gz 4.0 GB
EGAF00004176905 fq.gz 7.2 GB
EGAF00004176906 fq.gz 7.4 GB
EGAF00004176907 fq.gz 8.5 GB
EGAF00004176908 fq.gz 8.9 GB
EGAF00004176909 fq.gz 4.0 GB
EGAF00004176910 fq.gz 4.1 GB
EGAF00004176911 fq.gz 8.2 GB
EGAF00004176912 fq.gz 8.6 GB
EGAF00004176913 fq.gz 3.6 GB
EGAF00004176914 fq.gz 3.7 GB
EGAF00004176915 fq.gz 4.1 GB
EGAF00004176916 fq.gz 4.2 GB
EGAF00004176917 fq.gz 3.7 GB
EGAF00004176918 fq.gz 3.9 GB
EGAF00004176919 fq.gz 7.4 GB
EGAF00004176920 fq.gz 7.7 GB
EGAF00004176921 fq.gz 3.9 GB
EGAF00004176922 fq.gz 4.1 GB
EGAF00004176923 fq.gz 7.2 GB
EGAF00004176924 fq.gz 7.5 GB
EGAF00004176925 fq.gz 3.1 GB
EGAF00004176926 fq.gz 3.2 GB
EGAF00004176927 fq.gz 3.5 GB
EGAF00004176928 fq.gz 3.6 GB
EGAF00004176929 fq.gz 2.6 GB
EGAF00004176930 fq.gz 2.7 GB
EGAF00004176931 fq.gz 4.1 GB
EGAF00004176932 fq.gz 4.2 GB
EGAF00004176933 fq.gz 3.5 GB
EGAF00004176934 fq.gz 3.7 GB
EGAF00004176935 fq.gz 3.5 GB
EGAF00004176936 fq.gz 3.7 GB
EGAF00004176937 fq.gz 3.2 GB
EGAF00004176938 fq.gz 3.3 GB
EGAF00004176939 fq.gz 3.1 GB
EGAF00004176940 fq.gz 3.2 GB
EGAF00004176941 fq.gz 2.2 GB
EGAF00004176942 fq.gz 2.3 GB
EGAF00004176943 fq.gz 3.2 GB
EGAF00004176944 fq.gz 3.3 GB
EGAF00004176945 fq.gz 2.8 GB
EGAF00004176946 fq.gz 2.9 GB
EGAF00004176947 fq.gz 3.8 GB
EGAF00004176948 fq.gz 4.0 GB
EGAF00004176949 fq.gz 3.4 GB
EGAF00004176950 fq.gz 3.6 GB
EGAF00004176951 fq.gz 3.0 GB
EGAF00004176952 fq.gz 3.2 GB
EGAF00004176953 fq.gz 3.0 GB
EGAF00004176954 fq.gz 3.2 GB
EGAF00004176955 fq.gz 3.2 GB
EGAF00004176956 fq.gz 3.4 GB
EGAF00004176957 fq.gz 3.1 GB
EGAF00004176958 fq.gz 3.2 GB
EGAF00004176959 fq.gz 3.4 GB
EGAF00004176960 fq.gz 3.5 GB
EGAF00004176961 fq.gz 3.2 GB
EGAF00004176962 fq.gz 3.4 GB
EGAF00004176963 fq.gz 3.3 GB
EGAF00004176964 fq.gz 3.4 GB
EGAF00004176965 fq.gz 2.8 GB
EGAF00004176966 fq.gz 2.9 GB
EGAF00004176967 fq.gz 3.1 GB
EGAF00004176968 fq.gz 3.2 GB
EGAF00004176969 fq.gz 3.2 GB
EGAF00004176970 fq.gz 3.3 GB
EGAF00004176971 fq.gz 3.5 GB
EGAF00004176972 fq.gz 3.7 GB
EGAF00004176973 fq.gz 3.8 GB
EGAF00004176974 fq.gz 3.9 GB
EGAF00004176975 fq.gz 3.3 GB
EGAF00004176976 fq.gz 3.4 GB
EGAF00004176977 fq.gz 4.3 GB
EGAF00004176978 fq.gz 4.5 GB
EGAF00004176979 fq.gz 4.0 GB
EGAF00004176980 fq.gz 4.2 GB
EGAF00004176981 fq.gz 3.2 GB
EGAF00004176982 fq.gz 3.4 GB
EGAF00004176983 fq.gz 3.4 GB
EGAF00004176984 fq.gz 3.5 GB
EGAF00004176985 fq.gz 4.6 GB
EGAF00004176986 fq.gz 4.7 GB
EGAF00004176987 fq.gz 3.4 GB
EGAF00004176988 fq.gz 3.5 GB
EGAF00004176989 fq.gz 3.6 GB
EGAF00004176990 fq.gz 3.8 GB
EGAF00004176991 fq.gz 4.1 GB
EGAF00004176992 fq.gz 4.3 GB
EGAF00004176993 fq.gz 3.1 GB
EGAF00004176994 fq.gz 3.2 GB
EGAF00004176995 fq.gz 3.6 GB
EGAF00004176996 fq.gz 3.7 GB
EGAF00004176997 fq.gz 3.8 GB
EGAF00004176998 fq.gz 4.0 GB
EGAF00004176999 fq.gz 3.2 GB
EGAF00004177000 fq.gz 3.4 GB
EGAF00004177001 fq.gz 3.5 GB
EGAF00004177002 fq.gz 3.7 GB
EGAF00004177003 fq.gz 3.6 GB
EGAF00004177004 fq.gz 3.8 GB
EGAF00004177005 fq.gz 3.2 GB
EGAF00004177006 fq.gz 3.3 GB
EGAF00004177007 fq.gz 3.2 GB
EGAF00004177008 fq.gz 3.2 GB
EGAF00004177009 fq.gz 4.3 GB
EGAF00004177010 fq.gz 4.5 GB
EGAF00004177011 fq.gz 2.9 GB
EGAF00004177012 fq.gz 3.0 GB
EGAF00004177057 csv 7.0 MB
261 Files (620.3 GB)