Project

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Digital Cancer Biobank - zBioLink

English title Digital Cancer Biobank - zBioLink
Applicant Levesque Mitch
Number 172632
Funding scheme Biolink funds
Research institution Dermatologische Klinik Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Experimental Cancer Research
Start/End 01.02.2017 - 31.01.2020
Approved amount 441'500.00
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All Disciplines (5)

Discipline
Experimental Cancer Research
Clinical Cancer Research
Genetics
Molecular Biology
Information Technology

Keywords (8)

SLims; Cell Biobank; Drug Testing; Next Generation Sequencing; Oracle Translational Research Center; cBioPortal; Melanoma; Tissue Biobank

Lay Summary (German)

Lead
Prof. Peter WildProf. Mitch LevesequeProf. Gunnar Rätsch
Lay summary
Der jüngste dramatische Erfolg von Immun-Checkpoint-Inhibitoren war eine lange erwartete Revolution in der Krebsbehandlung. In Kombination mit der breiten Einführung von Next-Generation-Sequencing- und funktionellen Screening-Techniken verändert sich das Gesicht der biomedizinischen Forschung rapide. In Zukunft werden routinemäßige molekulare Analysen und in-vitro-pharmakologische Tests patientenspezifische Therapien unterstützen. Aber unser Verständnis, wie besondere genetische Merkmale dazu beitragen, therapeutische Reaktion vorherzusagen steckt noch in den Kinderschuhen. In diesem interdisziplinären BioLink-Projekt soll daher eine sog. digitale Biobank von Melanomproben und lebenden Zellen erzeugt werden, indem die Ressourcen von mindestens zwei Abteilungen (Dermatologie & Pathologie) miteinander verknüpft werden, wobei die genomischen und pharmakologischen Informationen bereits vorliegen. Dieses Projekt baut auf einer weltweit einzigartigen Sammlung von Gewebeproben und Datenerfassungstechniken auf. Um die Ergebnisse zu validieren ist es notwendig, die relevanten Daten und Proben in drei klar definierten Schritten zu sammeln. Im ersten Schritt wird ein Laborinformationssystem durch die Verknüpfung von zwei etablierten physikalischen Gewebe- und Zellbiobanken am UniversitätsSpital Zürich etabliert (Dermatologie & Pathologie). In einem zweiten Schritt werden Datenbankkapazitäten, Datenanalyse- und Visualisierungswerkzeuge zur Unterstützung der in silico Forschung mit den verfügbaren genomischen und klinischen Metadaten bereitgestellt. Dritter Schritt ist die Definition von rational gewählten Behandlungsschemata für jeden einzelnen Melanompatienten auf der Basis von ex vivo Testung von Proben. Unser Zwei-Jahres-Projekt wird durch die Konzentration auf das maligne Melanom initiiert und realisierbar gemacht. Zunächst wird ein Pilotprogramm mit 150 sorgfältig ausgewählten Melanompatienten durchgeführt. 
Direct link to Lay Summary Last update: 09.01.2017

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Peripheral Blood TCR Repertoire Profiling May Facilitate Patient Stratification for Immunotherapy against Melanoma
Hogan Sabrina A., Courtier Anaïs, Cheng Phil F., Jaberg-Bentele Nicoletta F., Goldinger Simone M., Manuel Manuarii, Perez Solène, Plantier Nadia, Mouret Jean-François, Nguyen-Kim Thi Dan Linh, Raaijmakers Marieke I.G., Kvistborg Pia, Pasqual Nicolas, Haanen John B.A.G., Dummer Reinhard, Levesque Mitchell P. (2019), Peripheral Blood TCR Repertoire Profiling May Facilitate Patient Stratification for Immunotherapy against Melanoma, in Cancer Immunology Research, 7(1), 77-85.

Collaboration

Group / person Country
Types of collaboration
SPHN Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Associated projects

Number Title Start Funding scheme
177080 MIG-ART - MRI gestützte adaptive Radio-Onkologie 01.06.2018 R'EQUIP

Abstract

The recent dramatic success of immune checkpoint inhibitors has been a long awaited revolution in cancer treatment. Combined with the broad adoption of next-generation-sequencing (NGS) and functional drug screening techniques, the face of biomedical research is changing rapidly. In the future, routine molecular analysis and in vitro pharmacological testing will support patient-tailored therapies. But our understanding of how particular features in high-dimensional datasets contribute to or predict therapeutic response is still in its infancy. Thus, the current proposal is intended to link various biobanks at the University Hospital Zürich (USZ) to follow-up on an initial study by the group of Prof. Mitch Levesque (co-leader of this proposal) that identified a significant predictive biomarker of response to both currently available immune checkpoint inhibitors in melanoma (anti-CTLA4 and anti-PD1).Clinical cancer specimens are unique and finite. They are also a critical foundation for precision medicine (PM). In general, clinical specimens such as blood, tissue or cell samples are annotated and stored in biospecimen banks (biobanks) that are typically associated with and maintained by a specific clinical center. In this interdisciplinary BioLink project, we propose to generate a digital biobank of melanoma specimens and living cells by linking the resources of at least two departments (Dept. of Dermatology & Pathology, and potentially Oncology and Hematology), where the genomic and pharmacological information is recorded and presented in searchable, digital files that are stored with the clinical metadata in a database. This pioneering project builds on a worldwide unique collection of tissue specimens and data acquisition techniques present in Zürich. It has the potential to transform PM by making data that represents the quantitative molecular and functional makeup of clinical samples accessible for research. This project will address the urgent clinical need of establishing a better stratification of metastatic melanoma patients for the most efficacious therapy. This will be based on the methods developed by the group of Prof. Levesque and recently presented at ASCO 2016. But in order to validate and expand their findings, it is necessary to gather the relevant data and samples from the USZ in three well-defined steps. The first is to establish the laboratory information system SLims (Genohm SA, Lausanne) by linking two established physical tissue and cell biobanks at the University Hospital Zürich (Dept. of Pathology and Dermatology), the second is to establish database capabilities, data analytics, and visualization tools (cBioPortal, The Hyve, Cambridge, USA) to support in silico research with the available genomic and clinical/phenotypic metadata, and the third is to define personalized, rationally chosen treatment regimens for each individual melanoma patient to prolong life after ex vivo pharmacologic testing of melanoma cells (precision medicine).We will meet these important challenges through the development and the implementation of a new, integrated strategy that is focused on the combined analysis of immune signatures and genetics as well as all available clinical parameters. Our two-year project will be initiated and made feasible by focusing on malignant melanoma and builds on the results and advances achieved by the project team. In the past, the applicants have successfully established facilities to convert physical specimens into digital files representing their genomic states. A pilot program of a carefully selected set of 150 specimens will be carried out, comparing features of tumors and matching living cells. Specifically, the unique technical capabilities and resources the project team will bring to bear on melanoma include 1) unique, annotated clinical tissue and cell resources including the two largest cancer tissue and cell biobanks in Switzerland, 2) technologies to generate genetic barcodes and drug response data of melanoma samples in a high-throughput manner, 3) a novel framework (Oracle Translational Research Center Platform) for linking metadata in the clinic, and 4) (bio-) informatics tools to define and visualize the networks perturbed in melanoma. Associated challenges will be solved by the development of a digital biobank application, using the cBioPortal software (The Hyve, Cambridge) that visualizes different biobanking initiatives. Another result and unique feature of the project will be the prospective generation of a digital biobank sui generis for all types of disease, called zBioLink. Besides conventional tissue and cell samples, sequencing results will be systematically collected and integrated with clinical outcome information and pharmacological in vitro data. The project will extend the current histopathological and genetic characterization of cancer tissue to the level of functional drug response data. In addition, the zBioLink project will establish a general framework for bringing basic research discoveries to the clinics for patients’ benefit and provide an environment for clinical and basic scientists to collaborate efficiently. The project team has already implemented a tumor-board in molecular-oncology and immuno-oncology at the University Hospital Zürich, where selected patients from the pilot study with metastatic disease can be discussed. Access to data will be provided by the Research Data Service Center, USZ. The project will democratize precision medicine research by linking these efforts and presenting the data of tissues and living cells in a graphical user interface (zBioLink). Linked biobank databases of this scale will facilitate the realization of systems medicine as a milestone on the way to an effective PM program that enables the identification of predictive biomarkers and potential drug targets across large cohorts of cancer patients. We anticipate that the project will be completed within two years. Alignment with national initiatives (Swiss Biobanking Platform, Swiss Institute of Bioinformatics) is intended to allow for collaborations and harmonization of standards across Switzerland.
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