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APERIM: Advanced bioinformatics platform for PERsonalised cancer IMmunotherapy

Deliverables

SOP for TCR repertoire

Evaluated and implemented SOPs. SOPs for TCR repertoire. Samples used for generating data to develop the tools and validate the software: melanoma, colorectal cancer, and ovarian cancer.

Evaluation of the analytical pipeline for cancer vaccines

Evaluated and implemented SOPs. Samples used for generating data to develop the tools and validate the software: melanoma, glioblastoma, and breast cancer.

CRCclassifier

A decision support model using the clinical parameters and the image descriptors derived from the analyses in task 2.1. The model will be a validated prototype using the available data. Samples used for generating data to develop the tools and validate the software: colorectal cancer.

SOPs for TIL quantification

Evaluated and implemented SOPs. SOPs for routine application in pathology labs. Samples used for generating data to develop the tools and validate the software: colorectal cancer.

TCR2epitope

Software tool for predicting epitope characteristics from the primary sequence information of TCRs. The software will include a method for identifying specificity of TCR-pMHC interaction (UU) as well as a web-database for TCRs with known specificities (MU). The data will be provided by NKI. Samples used for generating data to develop the tools and validate the software: melanoma, colorectal cancer, and ovarian cancer

Immuno Oncoclogy Suite

Database for molecular data (whole-exome sequencing data, microsatellite status, FACS data), clinical data (information about cancer patients, TNM staging, and density values of TILs used for immune score estimation), and imaging data (scanned whole-slide H&E images and stained IHC images) generated from colorectal cancer samples in WP2.

epitopeselector

Software for selecting epitopes from large number of candidates. Samples used for generating data to develop the tools and validate the software: melanoma, glioblastoma, and breast cancer.

RDF database

RDF version of the database ImmunoOncologySuite and SPARQL graphical editor

digital TILsorter

Method and software for TIL reconstruction employing a) deconvolution method (CNIC) and develop the algorithm for enumeration of immune cells, stromal cells, and tumour cells (I-MED). Samples used for generating data to develop the tools and validate the software: colorectal cancer.

Webpage

Institution of APERIM web page: A webpage is an absolute requirement for dissemination Furthermore it supports the communication within the consortium.

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Publications

Designing string-of-beads vaccines with optimal spacers

Author(s): Benjamin Schubert, Oliver Kohlbacher
Published in: Genome Medicine, Issue 8/1, 2016, Page(s) 1-10, ISSN 1756-994X
DOI: 10.1186/s13073-016-0263-6

FRED 2 – An Immunoinformatics Framework for Python

Author(s): Benjamin Schubert, Mathias Walzer, Hans-Philipp Brachvogel, András Szolek, Christopher Mohr, Oliver Kohlbacher
Published in: Bioinformatics, 2016, Page(s) btw113, ISSN 1367-4803
DOI: 10.1093/bioinformatics/btw113

qPortal: A platform for data-driven biomedical research

Author(s): Christopher Mohr, Andreas Friedrich, David Wojnar, Erhan Kenar, Aydin Can Polatkan, Marius Cosmin Codrea, Stefan Czemmel, Oliver Kohlbacher, Sven Nahnsen
Published in: PLOS ONE, Issue 13/1, 2018, Page(s) e0191603, ISSN 1932-6203
DOI: 10.1371/journal.pone.0191603

VDJdb: a curated database of T-cell receptor sequences with known antigen specificity

Author(s): Mikhail Shugay, Dmitriy V Bagaev, Ivan V Zvyagin, Renske M Vroomans, Jeremy Chase Crawford, Garry Dolton, Ekaterina A Komech, Anastasiya L Sycheva, Anna E Koneva, Evgeniy S Egorov, Alexey V Eliseev, Ewald Van Dyk, Pradyot Dash, Meriem Attaf, Cristina Rius, Kristin Ladell, James E McLaren, Katherine K Matthews, E Bridie Clemens, Daniel C Douek, Fabio Luciani, Debbie van Baarle, Katherine Kedzier
Published in: Nucleic Acids Research, Issue 46/D1, 2017, Page(s) D419-D427, ISSN 0305-1048
DOI: 10.1093/nar/gkx760

Neoantigens Generated by Individual Mutations and Their Role in Cancer Immunity and Immunotherapy

Author(s): Mirjana Efremova, Francesca Finotello, Dietmar Rieder, Zlatko Trajanoski
Published in: Frontiers in Immunology, Issue 8, 2017, ISSN 1664-3224
DOI: 10.3389/fimmu.2017.01679

Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade

Author(s): Pornpimol Charoentong, Francesca Finotello, Mihaela Angelova, Clemens Mayer, Mirjana Efremova, Dietmar Rieder, Hubert Hackl, Zlatko Trajanoski
Published in: Cell Reports, Issue 18/1, 2017, Page(s) 248-262, ISSN 2211-1247
DOI: 10.1016/j.celrep.2016.12.019

Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival

Author(s): Bernhard Mlecnik, Marc Van den Eynde, Gabriela Bindea, Sarah E Church, Angela Vasaturo, Tessa Fredriksen, Lucie Lafontaine, Nacilla Haicheur, Florence Marliot, Daphné Debetancourt, Géraldine Pairet, Anne Jouret-Mourin, Jean-Francois Gigot, Catherine Hubert, Etienne Danse, Cristina Dragean, Javier Carrasco, Yves Humblet, Viia Valge-Archer, Anne Berger, Franck Pagès, Jean-Pascal Machiels, Jérôm
Published in: JNCI: Journal of the National Cancer Institute, Issue 110/1, 2017, Page(s) 97-108, ISSN 0027-8874
DOI: 10.1093/jnci/djx123

Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution

Author(s): Mirjana Efremova, Dietmar Rieder, Victoria Klepsch, Pornpimol Charoentong, Francesca Finotello, Hubert Hackl, Natascha Hermann-Kleiter, Martin Löwer, Gottfried Baier, Anne Krogsdam, Zlatko Trajanoski
Published in: Nature Communications, Issue 9/1, 2018, ISSN 2041-1723
DOI: 10.1038/s41467-017-02424-0

Computational genomics tools for dissecting tumour–immune cell interactions

Author(s): Hubert Hackl, Pornpimol Charoentong, Francesca Finotello, Zlatko Trajanoski
Published in: Nature Reviews Genetics, Issue 17/8, 2016, Page(s) 441-458, ISSN 1471-0056
DOI: 10.1038/nrg.2016.67

Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability

Author(s): Bernhard Mlecnik, Gabriela Bindea, Helen K. Angell, Pauline Maby, Mihaela Angelova, David Tougeron, Sarah E. Church, Lucie Lafontaine, Maria Fischer, Tessa Fredriksen, Maristella Sasso, Amélie M. Bilocq, Amos Kirilovsky, Anna C. Obenauf, Mohamad Hamieh, Anne Berger, Patrick Bruneval, Jean-Jacques Tuech, Jean-Christophe Sabourin, Florence Le Pessot, Jacques Mauillon, Arash Rafii, Pierre Laure
Published in: Immunity, Issue 44/3, 2016, Page(s) 698-711, ISSN 1074-7613
DOI: 10.1016/j.immuni.2016.02.025

Targeting of cancer neoantigens with donor-derived T cell receptor repertoires

Author(s): E. Stronen, M. Toebes, S. Kelderman, M. M. van Buuren, W. Yang, N. van Rooij, M. Donia, M.-L. Boschen, F. Lund-Johansen, J. Olweus, T. N. Schumacher
Published in: Science, Issue 352/6291, 2016, Page(s) 1337-1341, ISSN 0036-8075
DOI: 10.1126/science.aaf2288

The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis

Author(s): B. Mlecnik, G. Bindea, A. Kirilovsky, H. K. Angell, A. C. Obenauf, M. Tosolini, S. E. Church, P. Maby, A. Vasaturo, M. Angelova, T. Fredriksen, S. Mauger, M. Waldner, A. Berger, M. R. Speicher, F. Pages, V. Valge-Archer, J. Galon
Published in: Science Translational Medicine, Issue 8/327, 2016, Page(s) 327ra26-327ra26, ISSN 1946-6234
DOI: 10.1126/scitranslmed.aad6352

ImmunoNodes – graphical development of complex immunoinformatics workflows

Author(s): Benjamin Schubert, Luis de la Garza, Christopher Mohr, Mathias Walzer, Oliver Kohlbacher
Published in: BMC Bioinformatics, Issue 18/1, 2017, ISSN 1471-2105
DOI: 10.1186/s12859-017-1667-z

New strategies for cancer immunotherapy: targeting regulatory T cells

Author(s): Francesca Finotello, Zlatko Trajanoski
Published in: Genome Medicine, Issue 9/1, 2017, ISSN 1756-994X
DOI: 10.1186/s13073-017-0402-8

TIminer: NGS data mining pipeline for cancer immunology and immunotherapy

Author(s): Elias Tappeiner, Francesca Finotello, Pornpimol Charoentong, Clemens Mayer, Dietmar Rieder, Zlatko Trajanoski
Published in: Bioinformatics, 2017, ISSN 1367-4803
DOI: 10.1093/bioinformatics/btx377

Application of nonsense-mediated primer exclusion (NOPE) for preparation of unique molecular barcoded libraries

Author(s): Dmitriy A. Shagin, Maria A. Turchaninova, Irina A. Shagina, Mikhail Shugay, Andrew R. Zaretsky, Olga I. Zueva, Dmitriy A. Bolotin, Sergey Lukyanov, Dmitriy M. Chudakov
Published in: BMC Genomics, Issue 18/1, 2017, ISSN 1471-2164
DOI: 10.1186/s12864-017-3815-2

MAGERI: Computational pipeline for molecular-barcoded targeted resequencing

Author(s): Mikhail Shugay, Andrew R. Zaretsky, Dmitriy A. Shagin, Irina A. Shagina, Ivan A. Volchenkov, Andrew A. Shelenkov, Mikhail Y. Lebedin, Dmitriy V. Bagaev, Sergey Lukyanov, Dmitriy M. Chudakov
Published in: PLOS Computational Biology, Issue 13/5, 2017, Page(s) e1005480, ISSN 1553-7358
DOI: 10.1371/journal.pcbi.1005480