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Nat Biotechnol2025;43(7):1035-1040.July 1, 2025Letter

Defining and benchmarking open problems in single-cell analysis.

Malte D Luecken1,2, Scott Gigante3, Daniel B Burkhardt4, Robrecht Cannoodt5,6,7, Daniel C Strobl1,8,9, Nikolay S Markov10, Luke Zappia1,5,11, Giovanni Palla1,9, Wesley Lewis12, Daniel Dimitrov13, Michael E Vinyard14,15,16, D S Magruder17, Michaela F Mueller1,2,9, Alma Andersson18,19,20, Emma Dann21, Qian Qin15, Dominik J Otto22,23,24, Michal Klein25, Olga Borisovna Botvinnik26,27, Louise Deconinck6,7, Kai Waldrant5, Sai Nirmayi Yasa5, Artur Szałata1,11, Andrew Benz28, Zhijian Li15,16, , Jonathan M Bloom29, Angela Oliveira Pisco26,30, Julio Saez-Rodriguez13, Drausin Wulsin3, Luca Pinello16, Yvan Saeys6,7,31, Fabian J Theis32,33,34, Smita Krishnaswamy35,36,37
1Institute of Computational Biology, Helmholtz Munich, Neuherberg, Germany.
2Institute of Lung Health & Immunity, Helmholtz Munich; Member of the German Center for Lung Research (DZL), Munich, Germany.
3Immunai, New York, USA.
4NVIDIA, Santa Clara, CA, USA.
5Data Intuitive, Lebbeke, Belgium.
6Data Mining and Modelling for Biomedicine group, VIB Center for Inflammation Research, Ghent, Belgium.
7Department of Applied Mathematics, Computer Science, and Statistics, Ghent University, Ghent, Belgium.
8Institute of Clinical Chemistry and Pathobiochemistry, School of Medicine, Technical University of Munich, Munich, Germany.
9TUM School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany.
10Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
11Department of Mathematics, School of Computing, Information and Technology, Technical University of Munich, Munich, Germany.
12Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.
13Faculty of Medicine and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg University, Heidelberg, Germany.
14Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
15Broad Institute of MIT and Harvard, Cambridge, MA, USA.
16Molecular Pathology Unit, Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
17Department of Computer Science, Yale University, New Haven, CT, USA.
18Genentech Inc, South San Francisco, CA, USA.
19Gene Technology, Royal Institute of Technology (KTH), Stockholm, Sweden.
20Science for Life Laboratory (SciLifeLab), Solna, Sweden.
21Wellcome Sanger Institute, Cambridge, UK.
22Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
23Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
24Translational Data Science IRC, Fred Hutchinson Cancer Center, Seattle, WA, USA.
25Apple, Paris, France.
26Data Sciences Platform, Chan Zuckerberg Biohub, San Francisco, CA, USA.
27Bridge Bio Pharma, Palo Alto, CA, USA.
28Cellarity, Inc, Somerville, MA, USA.
29Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, USA.
30Insitro, South San Francisco, USA.
31VIB Center for AI & Computational Biology (VIB.AI), Ghent, Belgium.
32Institute of Computational Biology, Helmholtz Munich, Neuherberg, Germany. fabian.theis@helmholtz-munich.de.
33Department of Mathematics, School of Computing, Information and Technology, Technical University of Munich, Munich, Germany. fabian.theis@helmholtz-munich.de.
34Cellular Genetics Programme, Wellcome Sanger Institute, Hinxton, UK. fabian.theis@helmholtz-munich.de.
35Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA. smita.krishnaswamy@yale.edu.
36Department of Computer Science, Yale University, New Haven, CT, USA. smita.krishnaswamy@yale.edu.
37Department of Genetics, Yale University, New Haven, CT, USA. smita.krishnaswamy@yale.edu.
PubMed DOI

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