EN
Infrastructure INF:
Central Data- and Biobank
Project leaders:
PD Dr. med. Marcial Sebode, PhD
Prof. Dr. med. Frank Ückert
Summary
The proposed CRC has a clear vision to elucidate the mechanisms of hepatic immune regulation. In order to do so, the analysis of human biomaterial is vital. The aim of this infrastructure project is to create a versatile and flexible IT infrastructure in order to maximise the benefit derived from human data and biomaterial for all PIs of this consortium. This will be achieved through a central and fair coordination of the respective needs, the standardised acquisition, processing and storage of human biomaterial and the management of clinical and experimental data. Fresh tru-cut liver biopsies and surgery-derived biomaterial will be processed as needed by the respective projects. In addition, liver tissue, peripheral venous blood mononuclear cells, serum, bile fluid, stool and urine have already been collected in a central biobank that will be further expanded within this CRC. The centralised sample acquisition and processing will increase quality through adherence to standard operating procedures (SOP) and maximise the efficient use of human biomaterial for the whole consortium. A study protocol for fine-needle aspiration (FNA) liver biopsies will be established to provide liver tissue for immune cell deep phenotyping studies and to enable follow-up tissue sampling during the course of disease in the future. The Central Data- and Biobank will be integrated into a technical infrastructure, strictly complying with the European Union General Data Protection Regulation (EU GDPR), that implements a semantic data integration platform to allow interactive querying and innovative data-centred visualisations to increase accessibility of biomaterial and clinical as well as experimental data for the whole CRC. We will liaise with Bonn, Zolotareva & Baumbach (SP01) to enable their synergistic data analysis. The focus of this project is twofold: 1) The Central Data- and Biobank will serve the consortium to reach the specific project aims by providing a large, high-quality biobank with clinically well-characterised biosamples. 2) An innovative, flexible and advanced data integration platform is provided that allows the merging of clinical, omics and experimental human-derived data. The platform also includes a user-centred visualisation infrastructure.
Project plan
Our central infrastructure project is to support the consortium in reaching the specific project aims by providing a large, high-quality biobank with clinically well-characterised biosamples and an IT infrastructure with integration of clinical and omics data. In order to achieve this goal, our work programme includes three work packages (WPs) intended to meet the following objectives (summarised in graphical abstract):
WP1: To guarantee high-quality biobanking and the coordinated distribution of biosamples according to the needs of individual CRC projects.
WP2: To develop a protocol for and apply fine-needle aspiration (FNA) of liver tissue for serial biopsies.
WP3: To provide a central IT infrastructure for the whole CRC.
Project related publications
Poch T#, Krause J#, Casar C, Liwinski T, Glau L, Kaufmann M, Ahrenstorf AE, Hess LU, Ziegler AE, Martrus G, Lunemann S, Sebode M, Li J, Schwinge D, Krebs CF, Franke A, Friese MA, Oldhafer KJ, Fischer L, Altfeld M, Lohse AW, Huber S, Tolosa E#, Gagliani N#, Schramm C#. Single-cell atlas of hepatic T cells reveals expansion of liver-resident naive-like CD4+ T cells in primary sclerosing cholangitis. J Hepatol 2021;75:414-423. doi: 10.1016/j.jhep.2021.03.016. Open Access.
Dudek M, Pfister D, Donakonda S, Filpe P, Schneider A, Laschinger M, Hartmann D, Hüser N, Meiser P, Bayerl F, Inverso D, Wigger J, Sebode M, Öllinger R, Rad R, Hegenbarth S, Anton M, Guillot A, Bowman A, Heide D, Müller F, Ramadori P, Leone V, Garcia-Caceres C, Gruber T, Seifert G, Kabat AM, Mallm JP, Reider S, Effenberger M, Roth S, Billeter AT, Müller-Stich B, Pearce EJ, Koch-Nolte F, Käser R, Tilg H, Thimme R, Boettler T, Tacke F, Dufour JF, Haller D, Murray PJ, Heeren R, Zehn D, Böttcher JP, Heikenwälder M, Knolle PA. Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH. Nature 2021;592:444-449. doi: 10.1038/s41586-021-03233-8.
van Heesch S, Witte F, Schneider-Lunitz V, Schulz JF, Adami E, Faber AB, Kirchner M, Maatz H, Blachut S, Sandmann CL, Kanda M, Worth CL, Schafer S, Calviello L, Merriott R, Patone G, Hummel O, Wyler E, Obermayer B, Mücke MB, Lindberg EL, Trnka F, Memczak S, Schilling M, Felkin LE, Barton PJR, Quaife NM, Vanezis K, Diecke S, Mukai M, Mah N, Oh SJ, Kurtz A, Schramm C, Schwinge D, Sebode M, Harakalova M, Asselbergs FW, Vink A, de Weger RA, Viswanathan S, Widjaja AA, Gärtner-Rommel A, Milting H, Dos Remedios C, Knosalla C, Mertins P, Landthaler M, Vingron M, Linke WA, Seidman JG, Seidman CE, Rajewsky N, Ohler U, Cook SA, Hubner N. The Translational Landscape of the Human Heart. Cell 2019;178:242-260.e29. doi: 10.1016/j.cell.2019.05.010. Open Access.
Sebode M#, Peiseler M#, Franke B, Schwinge D, Schoknecht T, Wortmann F, Quaas A, Petersen BS, Ellinghaus E, Baron U, Olek S, Wiegard C, Weiler-Normann C, Lohse AW, Herkel J, Schramm C. Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms. J Hepatol 2014;60:1010-6. doi: 10.1016/j.jhep.2013.12.027.
Peiseler M#, Sebode M#, Franke B, Wortmann F, Schwinge D, Quaas A, Baron U, Olek S, Wiegard C, Lohse AW, Weiler-Normann C, Schramm C, Herkel J. FOXP3+ regulatory T cells in autoimmune hepatitis are fully functional and not reduced in frequency. J Hepatol 2012;57:125-32. doi: 10.1016/j.jhep.2012.02.029.
Lablans M, Schmidt EE, Ückert F. An Architecture for Translational Cancer Research As Exemplified by the German Cancer Consortium. JCO Clin Cancer Inform 2018;2:1-85. doi: 10.1200/CCI.17.00062.
Lauk K, Peters M-C, Velthaus J-L, Nürnberg S, Ückert F. Use of Process Modelling for Optimization of Molecular Tumour Boards. Applied Sciences 2022;12:3485. https://doi.org/10.3390/ app12073485. Open access.
Ahlbrandt J, Lablans M, Glocker K, Stahl-Toyota S, Maier-Hein K, Maier-Hein L, Ückert F. Modern Information Technology for Cancer Research: What's in IT for Me? An Overview of Technologies and Approaches. Oncology 2020;98:363-369. doi: 10.1159/000493638. Open access.
Glocker K, Ahlbrandt J, Knurr A, Horak P, Heining C, Ückert F. Finding Options Beyond Standard of Care in Oncology: A Proposal for Workflows Utilizing Knowledge Databases. Stud Health Technol Inform 2019;264:950-953. doi: 10.3233/SHTI190364.
Proynova R, Alexandre D, Lablans M, Van Enckevort D, Mate S, Eklund N, Silander K, Hummel M, Holub P, Ückert F. A Decentralized IT Architecture for Locating and Negotiating Access to Biobank Samples. Stud Health Technol Inform 2017;243:75-79.
# equally contributing authors