Benchmarked approaches for reconstruction of in vitro cell lineages and in silico models of C. elegans and M. musculus developmental trees
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The recent advent of CRISPR and other molecular tools enabled the reconstruction of cell lineages based on induced DNA mutations and promises to solve the ones of more complex organisms. To date, no lineage reconstruction algorithms have been rigorously examined for their performance and robustness across dataset types and number of cells. To benchmark such methods, we decided to organize a DREAM challenge using in vitro experimental intMEMOIR recordings and in silico data for a C. elegans lineage tree of about 1,000 cells and a Mus musculus tree of 10,000 cells. Some of the 22 approaches submitted had excellent performance, but structural features of the trees prevented optimal reconstructions. Using smaller sub-trees as training sets proved to be a good approach for tuning algorithms to reconstruct larger trees. The simulation and reconstruction methods here generated delineate a potential way forward for solving larger cell lineage trees such as in mouse.
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Reconstruction performance of lineage tracing algorithms is difficult to assess because they might highlight different parts of the lineages well.
“Reconstruction performance of algorithms is difficult to assess, as they might highlight different parts of the lineages well75.”
From Best practices for single-cell analysis across modalities (2023) · cites this paper as [75]
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Hu, J., Jeong, H.-H., Al‐Ouran, R., Bado, I., Zhang, W., Zhang, X. H.-F., & Liu, Z. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.29.466515
Self-citationDCLEAR: Distance Based Cell Lineage Reconstruction
Kwak, I., & Gong, W. (2021) · doi:10.32614/cran.package.dclear
Self-citationTree reconstruction guarantees from CRISPR-Cas9 lineage tracing data using Neighbor-JoiningPreprint
Prillo, S., An, K., Wu, W., Kristanto, I., Jones, M. G., Song, Y. S., & Yosef, N. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.27.610007
Self-citationComputational Methods for Lineage Reconstruction
Salvador‐Martínez, I. (2025) · Methods in molecular biology · doi:10.1007/978-1-0716-4310-5_18
Self-citationAnderson, D. J., & Horwitz, M. S. (2025) · Methods in molecular biology · doi:10.1007/978-1-0716-4310-5_1
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Self-citationChen, Z., Zhang, B., Tang, L., Gong, F., Wan, L., & Ma, L. (2026) · Genome Research · doi:10.1101/gr.281460.125
Integrative Inference of Spatially Resolved Cell Lineage Trees using LineageMapPreprint
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Zhang, Z., Li, Y., Peng, Y., Ling, R., Li, K., Cheng, M., Cheng, Y., Zhang, C., Wang, X., Chen, S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.14.759016
- Authors
- Gong, W., Granados, A. A., Hu, J., Jones, M. G., Raz, O., Salvador-Martínez, I., Zhang, H., Chow, K.-H. K., Kwak, I.-Y., Retkute, R., Prusokiene, A., Prusokas, A., Khodaverdian, A., Zhang, R., Rao, S., Wang, R., Rennert, P., Saipradeep, V. G., Sivadasan, N., Rao, A., Joseph, T., Srinivasan, R., Peng, J., Han, L., Shang, X., Garry, D. J., Yu, T., Chung, V., Mason, M., Liu, Z., Guan, Y., Yosef, N., Shendure, J., Telford, M. J., Shapiro, E., Elowitz, M. B., & Meyer, P.
- Affiliations
- University of Minnesota (US)
- California Institute of Technology (US)
- Baylor College of Medicine (US)
- University of California, San Francisco (US)
- Weizmann Institute of Science (IL)
- University of Michigan (US)
- Chung-Ang University (KR)
- Newcastle University (GB)
- Imperial College London (GB)
- University of California, Berkeley (US)
- Tata Consultancy Services (India) (IN)
- Northwestern Polytechnical University (CN)
- Sage Bionetworks (US)
- Howard Hughes Medical Institute (US)
- University College London (GB)
- IBM (United States) (US)
- Corresponding author
- Meyer, Pablo
- ORCID
- Gong, Wuming
- Granados, Alejandro A.
- Hu, Jingyuan
- Jones, Matthew G.
- Raz, Ofir
- Zhang, Hanrui
- Kwak, Il-Youp
- Khodaverdian, Alex
- Wang, Robert
- Rao, Aditya
- Joseph, Thomas
- Peng, Jiajie
- Han, Lu
- Shang, Xuequn
- Garry, Daniel J.
- Yu, Thomas
- Chung, Verena
- Liu, Zhandong
- Guan, Yuanfang
- Yosef, Nir
- Shendure, Jay
- Telford, Maximilian J.
- Shapiro, Ehud
- Elowitz, Michael B.
- Meyer, Pablo
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 12
- Issue
- 8
- Pages
- 810-826.e4
- ISSN
- 2405-4712 (ISSN-L)
- OpenAlex
- W3171133702
- Cited by
- 62
- References
- 43
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 9 · 2023: 14 · 2022: 12 · 2021: 3
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Systems (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- UCL Discovery (University College London) (submittedVersion)
- Apollo
- Funders
- Horowitz Foundation for Social Policy (RGP0002/2016)
- Human Frontier Science Program (2020)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- cell lineage reconstruction, DREAM challenge, benchmarking, CRISPR mutagenesis, Caenorhabditis elegans, Mus musculus, training data size, single-cell lineage tracing
- MeSH terms
- Algorithms, Animals, Computer Simulation, Caenorhabditis elegans, Cell Lineage, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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