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12 Grand Challenges in Single-Cell Data Science

  • Laehnemann, David ORCID Computational Biology of Infection Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany
  • Köster, Johannes ORCID Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, United States of America
  • Szczurek, Ewa Institute of Informatics, Faculty of Mathematics, Informatics and Mechanics University of Warsaw, Warsaw, Poland
  • McCarthy, Davis J ORCID Melbourne Integrative Genomics, School of BioSciences / School of Mathematics & Statistics, Faculty of Science, University of Melbourne, Melbourne, Australia
  • Hicks, Stephanie C ORCID Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland, United States of America
  • Robinson, Mark D ORCID Institute of Molecular Life Sciences and SIB Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland
  • Vallejos, Catalina A The Alan Turing Institute, British Library, London, United Kingdom
  • Beerenwinkel, Niko SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
  • Campbell, Kieran R Data Science Institute, University of British Columbia, Vancouver, Canada
  • Mahfouz, Ahmed ORCID Delft Bioinformatics Lab, Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology, Delft, The Netherlands
  • Pinello, Luca Broad Institute of Harvard and MIT, Cambridge, Massachusets, United States of America
  • Skums, Pavel Department of Computer Science, Georgia State University, Atlanta, United States of America
  • Stamatakis, Alexandros ORCID Institute for Theoretical Informatics, Karlsruhe Institute of Technology, Karlsruhe, Germany
  • Stephan-Otto Attolini, Camille Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Barcelona, Spain
  • Aparicio, Samuel Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
  • Baaijens, Jasmijn Life Sciences and Health, Centrum Wiskunde & Informatica, Amsterdam, The Netherlands
  • Balvert, Marleen Theoretical Biology and Bioinformatics, Science for Life, Utrecht University, Utrecht, The Netherlands
  • de Barbanson, Buys Quantitative biology, Hubrecht Institute, Utrecht, The Netherlands
  • Cappuccio, Antonio Institute for Advanced Study, University of Amsterdam, Amsterdam, The Netherlands
  • Corleone, Giacomo Department of Surgery and Cancer, The Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, United Kingdom
  • Dutilh, Bas E ORCID Centre for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, The Netherlands
  • Florescu, Maria ORCID Quantitative biology, Hubrecht Institute, Utrecht, The Netherlands
  • Guryev, Victor European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • Holmer, Rens ORCID Bioinformatics Group, Wageningen University, Wageningen, The Netherlands
  • Jahn, Katharina SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
  • Jessurun Lobo, Thamar ORCID European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • Keizer, Emma M Biometris, Wageningen University & Research, Wageningen, The Netherlands
  • Khatri, Indu ORCID Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
  • Kiełbasa, Szymon M ORCID Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
  • Korbel, Jan O Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
  • Kozlov, Alexey M ORCID Computational Molecular Evolution Group, Heidelberg Institute for Theoretical Studies, Heidelberg, Germany
  • Kuo, Tzu-Hao Computational Biology of Infection Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany
  • Lelieveldt, Boudewijn PF Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
  • Mandoiu, Ion I ORCID Computer Science & Engineering Department, University of Connecticut, Storrs, United States of America
  • Marioni, John C European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom
  • Marschall, Tobias ORCID Max Planck Institute for Informatics, Saarbrücken, Germany
  • Mölder, Felix ORCID Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
  • Niknejad, Amir Mathematics department, Mount Saint Vincent, New York, United States of America
  • Rączkowski, Łukasz Institute of Informatics, Faculty of Mathematics, Informatics and Mechanics University of Warsaw, Warsaw, Poland
  • Reinders, Marcel Delft Bioinformatics Lab, Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology, Delft, The Netherlands
  • de Ridder, Jeroen ORCID Oncode Institute, Utrecht, The Netherlands
  • Saliba, Antoine-Emmanuel ORCID Helmholtz Institute for RNA-based Infection Research, Helmholtz-Center for Infection Research, Würzburg, Germany
  • Somarakis, Antonios Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
  • Stegle, Oliver Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Theis, Fabian J Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany
  • Yang, Huan Division of Drug Discovery and Safety, Leiden Academic Center for Drug Research (LACDR) / Leiden University, Leiden, The Netherlands
  • Zelikovsky, Alex The Laboratory of Bioinformatics, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
  • McHardy, Alice C Computational Biology of Infection Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany
  • Raphael, Benjamin J Department of Computer Science, Princeton University, Princeton, United States of America
  • Shah, Sohrab P Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United States of America
  • Schönhuth, Alexander Theoretical Biology and Bioinformatics, Science for Life, Utrecht University, Utrecht, The Netherlands
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English The recent upswing of microfluidics and combinatorial indexing strategies, further enhanced by very low sequencing costs, have turned single cell sequencing into an empowering technology; analyzing thousands—or even millions—of cells per experimental run is becoming a routine assignment in laboratories worldwide. As a consequence, we are witnessing a data revolution in single cell biology. Although some issues are similar in spirit to those experienced in bulk sequencing, many of the emerging data science problems are unique to single cell analysis; together, they give rise to the new realm of 'Single-Cell Data Science'.
Here, we outline twelve challenges that will be central in bringing this new field forward. For each challenge, the current state of the art in terms of prior work is reviewed, and open problems are formulated, with an emphasis on the research goals that motivate them.
This compendium is meant to serve as a guideline for established researchers, newcomers and students alike, highlighting interesting and rewarding problems in 'Single-Cell Data Science' for the coming years.
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