Abstract Spatial transcriptomics enables in-depth molecular characterization of samples on a morphology and RNA level while preserving spatial location. Integrating the resulting multi-modal data is an unsolved problem, and developing new solutions in precision medicine depends on improved methodologies. Here, we introduce AESTETIK, a convolutional deep learning model that jointly integrates spatial, transcriptomics, and morphology information to learn accurate spot representations. AESTETIK yielded substantially improved cluster assignments on widely adopted technology platforms (e.g., 10x Genomics™, NanoString™) across multiple datasets. We achieved performance enhancement on structured tissues (e.g., brain) with a 21% increase in median ARI over previous state-of-the-art methods. Notably, AESTETIK also demonstrated superior performance on cancer tissues with heterogeneous cell populations, showing a two-fold increase in breast cancer, 79% in melanoma, and 21% in liver cancer. We expect that these advances will enable a multi-modal understanding of key biological processes.

Authors Kalin Nonchev, Sonali Andani, Joanna Ficek-Pascual, Marta Nowak, Bettina Sobottka, Tumor Profiler Consortium, Viktor Hendrik Koelzer, and Gunnar Rätsch

Submitted MedRxiv

Link DOI

Authors Sarah Volinsky-Fremond, Nanda Horeweg, Sonali Andani, Jurriaan Barkey Wolf, Maxime W. Lafarge, Cor D. de Kroon, Gitte Ørtoft, Estrid Høgdall, Jouke Dijkstra, Jan J. Jobsen, Ludy C. H. W. Lutgens, Melanie E. Powell, Linda R. Mileshkin, Helen Mackay, Alexandra Leary, Dionyssios Katsaros, Hans W. Nijman, Stephanie M. de Boer, Remi A. Nout, Marco de Bruyn, David Church, Vincent T. H. B. M. Smit, Carien L. Creutzberg, Viktor H. Koelzer & Tjalling Bosse

Submitted Nature Medicine

DOI

Authors Sonali Andani, Boqi Chen, Joanna Ficek-Pascual, Simon Heinke, Ruben Casanova, Bettina Sobottka, Bernd Bodenmiller, Tumor Profiler Consortium, Viktor H Kölzer, Gunnar Rätsch

Submitted medRxiv

Authors Nikolaos Papandreou, Sonali Andani, Andreea Anghel, Milos Stanisavljevic

Submitted US Patent 16822136

Authors Sarah Fremond, Sonali Andani, Jurriaan Barkey Wolf, Jouke Dijkstra, Sinéad Melsbach, Jan J. Jobsen, Mariel Brinkhuis, Suzan Roothaan, Ina Jurgenliemk-Schulz, Ludy CHW. Lutgens, Remi A. Nout, Elzbieta M. van der Steen-Banasik, Stephanie M. de Boer, Melanie E. Powell, Naveena Singh, Linda R. Mileshkin, Helen J. Mackay, Alexandra Leary, Hans W. Nijman, Vincent T.H.B.M. Smit, Carien L. Creutzberg, Nanda Horeweg, Viktor H Koelzer, Tjalling Bosse

Submitted The Lancet Digital Health (accepted)

Abstract The application and integration of molecular profiling technologies create novel opportunities for personalized medicine. Here, we introduce the Tumor Profiler Study, an observational trial combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making with an exploratory approach to improve the biological understanding of the disease.

Authors Anja Irmisch, Ximena Bonilla, Stéphane Chevrier, Kjong-Van Lehmann, Franziska Singer, Nora C. Toussaint, Cinzia Esposito, Julien Mena, Emanuela S. Milani, Ruben Casanova, Daniel J. Stekhoven, Rebekka Wegmann, Francis Jacob, Bettina Sobottka, Sandra Goetze, Jack Kuipers, Jacobo Sarabia del Castillo, Michael Prummer, Mustafa A. Tuncel, Ulrike Menzel, Andrea Jacobs, Stefanie Engler, Sujana Sivapatham, Anja L. Frei, Gabriele Gut, Joanna Ficek-Pascual, Nicola Miglino, Melike Ak, Faisal S. Al-Quaddoomi, Jonas Albinus, Ilaria Alborelli, Sonali Andani, Per-Olof Attinger, Daniel Baumhoer, Beatrice Beck-Schimmer, Lara Bernasconi, Anne Bertolini, Natalia Chicherova, Maya D'Costa, Esther Danenberg, Natalie Davidson, Monica-Andreea Drăgan, Martin Erkens, Katja Eschbach, André Fedier, Pedro Ferreira, Bruno Frey, Linda Grob, Detlef Günther, Martina Haberecker, Pirmin Haeuptle, Sylvia Herter, Rene Holtackers, Tamara Huesser, Tim M. Jaeger, Katharina Jahn, Alva R. James, Philip M. Jermann, André Kahles, Abdullah Kahraman, Werner Kuebler, Christian P. Kunze, Christian Kurzeder, Sebastian Lugert, Gerd Maass, Philipp Markolin, Julian M. Metzler, Simone Muenst, Riccardo Murri, Charlotte K.Y. Ng, Stefan Nicolet, Marta Nowak, Patrick G.A. Pedrioli, Salvatore Piscuoglio, Mathilde Ritter, Christian Rommel, María L. Rosano-González, Natascha Santacroce, Ramona Schlenker, Petra C. Schwalie, Severin Schwan, Tobias Schär, Gabriela Senti, Vipin T. Sreedharan, Stefan Stark, Tinu M. Thomas, Vinko Tosevski, Marina Tusup, Audrey Van Drogen, Marcus Vetter, Tatjana Vlajnic, Sandra Weber, Walter P. Weber, Michael Weller, Fabian Wendt, Norbert Wey, Mattheus H.E. Wildschut, Shuqing Yu, Johanna Ziegler, Marc Zimmermann, Martin Zoche, Gregor Zuend, Rudolf Aebersold, Marina Bacac, Niko Beerenwinkel, Christian Beisel, Bernd Bodenmiller, Reinhard Dummer, Viola Heinzelmann-Schwarz, Viktor H. Koelzer, Markus G. Manz, Holger Moch, Lucas Pelkmans, Berend Snijder, Alexandre P.A. Theocharides, Markus Tolnay, Andreas Wicki, Bernd Wollscheid, Gunnar Rätsch, Mitchell P. Levesque

Submitted Cancer Cell (Commentary)

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