Tree Reconstruction Guarantees from CRISPR-Cas9 Lineage Tracing Data Using Neighbor-Joining

Sebastian Prillo; Kevin An; Wilson Wu; Ivan Kristanto; Matthew G. Jones; Yun S. Song; Nir Yosef

doi:10.1007/978-3-031-90252-9_43

Tree Reconstruction Guarantees from CRISPR-Cas9 Lineage Tracing Data Using Neighbor-Joining

Sebastian Prillo, Kevin An, Wilson Wu, Ivan Kristanto, Matthew G. Jones, Yun S. Song, Nir Yosef

Department of Systems Immunology

Weizmann Institute of Science

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

Abstract

CRISPR-Cas9 based lineage tracing technologies have enabled the reconstruction of single-cell phylogenies from transcriptional readouts. However, developing tree-reconstruction algorithms with theoretical guarantees in this setting is challenging. In this work, we derive a reconstruction algorithm with theoretical guarantees using Neighbor-Joining (NJ) on distances that are moment-matched to estimate the true tree distances. We develop a series of tools to analyze this algorithm and prove its theoretical guarantees. Empirically, we show on both simulated lineage tracing data and on real data from a mouse model of lung cancer the improved performance of our method as compared to the traditional use of NJ.

Original language	English
Title of host publication	Research in Computational Molecular Biology - 29th International Conference, RECOMB 2025, Proceedings
Editors	Sriram Sankararaman
Publisher	Springer Science and Business Media B.V.
Pages	376-380
Number of pages	5
ISBN (Print)	9783031902512
DOIs	https://doi.org/10.1007/978-3-031-90252-9_43
State	Published - 25 Apr 2025
Event	29th International Conference on Research in Computational Molecular Biology, RECOMB 2025 - Seoul, Korea, Republic of Duration: 26 Apr 2025 → 29 Apr 2025

Publication series

Name	Lecture Notes in Computer Science
Volume	15647 LNBI
ISSN (Print)	0302-9743

Conference

Conference	29th International Conference on Research in Computational Molecular Biology, RECOMB 2025
Country/Territory	Korea, Republic of
City	Seoul
Period	26/04/25 → 29/04/25

All Science Journal Classification (ASJC) codes

Theoretical Computer Science
General Computer Science

Access to Document

10.1007/978-3-031-90252-9_43

Cite this

Prillo, S., An, K., Wu, W., Kristanto, I., Jones, M. G., Song, Y. S., & Yosef, N. (2025). Tree Reconstruction Guarantees from CRISPR-Cas9 Lineage Tracing Data Using Neighbor-Joining. In S. Sankararaman (Ed.), Research in Computational Molecular Biology - 29th International Conference, RECOMB 2025, Proceedings (pp. 376-380). (Lecture Notes in Computer Science; Vol. 15647 LNBI). Springer Science and Business Media B.V.. https://doi.org/10.1007/978-3-031-90252-9_43

Prillo, Sebastian ; An, Kevin ; Wu, Wilson et al. / Tree Reconstruction Guarantees from CRISPR-Cas9 Lineage Tracing Data Using Neighbor-Joining. Research in Computational Molecular Biology - 29th International Conference, RECOMB 2025, Proceedings. editor / Sriram Sankararaman. Springer Science and Business Media B.V., 2025. pp. 376-380 (Lecture Notes in Computer Science).

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title = "Tree Reconstruction Guarantees from CRISPR-Cas9 Lineage Tracing Data Using Neighbor-Joining",

abstract = "CRISPR-Cas9 based lineage tracing technologies have enabled the reconstruction of single-cell phylogenies from transcriptional readouts. However, developing tree-reconstruction algorithms with theoretical guarantees in this setting is challenging. In this work, we derive a reconstruction algorithm with theoretical guarantees using Neighbor-Joining (NJ) on distances that are moment-matched to estimate the true tree distances. We develop a series of tools to analyze this algorithm and prove its theoretical guarantees. Empirically, we show on both simulated lineage tracing data and on real data from a mouse model of lung cancer the improved performance of our method as compared to the traditional use of NJ.",

author = "Sebastian Prillo and Kevin An and Wilson Wu and Ivan Kristanto and Jones, {Matthew G.} and Song, {Yun S.} and Nir Yosef",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive license to Springer Nature Switzerland AG 2025.; 29th International Conference on Research in Computational Molecular Biology, RECOMB 2025 ; Conference date: 26-04-2025 Through 29-04-2025",

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doi = "10.1007/978-3-031-90252-9_43",

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series = "Lecture Notes in Computer Science",

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Prillo, S, An, K, Wu, W, Kristanto, I, Jones, MG, Song, YS & Yosef, N 2025, Tree Reconstruction Guarantees from CRISPR-Cas9 Lineage Tracing Data Using Neighbor-Joining. in S Sankararaman (ed.), Research in Computational Molecular Biology - 29th International Conference, RECOMB 2025, Proceedings. Lecture Notes in Computer Science, vol. 15647 LNBI, Springer Science and Business Media B.V., pp. 376-380, 29th International Conference on Research in Computational Molecular Biology, RECOMB 2025, Seoul, Korea, Republic of, 26/04/25. https://doi.org/10.1007/978-3-031-90252-9_43

Tree Reconstruction Guarantees from CRISPR-Cas9 Lineage Tracing Data Using Neighbor-Joining. / Prillo, Sebastian; An, Kevin; Wu, Wilson et al.
Research in Computational Molecular Biology - 29th International Conference, RECOMB 2025, Proceedings. ed. / Sriram Sankararaman. Springer Science and Business Media B.V., 2025. p. 376-380 (Lecture Notes in Computer Science; Vol. 15647 LNBI).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

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T1 - Tree Reconstruction Guarantees from CRISPR-Cas9 Lineage Tracing Data Using Neighbor-Joining

AU - Prillo, Sebastian

AU - An, Kevin

AU - Wu, Wilson

AU - Kristanto, Ivan

AU - Jones, Matthew G.

AU - Song, Yun S.

AU - Yosef, Nir

PY - 2025/4/25

Y1 - 2025/4/25

N2 - CRISPR-Cas9 based lineage tracing technologies have enabled the reconstruction of single-cell phylogenies from transcriptional readouts. However, developing tree-reconstruction algorithms with theoretical guarantees in this setting is challenging. In this work, we derive a reconstruction algorithm with theoretical guarantees using Neighbor-Joining (NJ) on distances that are moment-matched to estimate the true tree distances. We develop a series of tools to analyze this algorithm and prove its theoretical guarantees. Empirically, we show on both simulated lineage tracing data and on real data from a mouse model of lung cancer the improved performance of our method as compared to the traditional use of NJ.

AB - CRISPR-Cas9 based lineage tracing technologies have enabled the reconstruction of single-cell phylogenies from transcriptional readouts. However, developing tree-reconstruction algorithms with theoretical guarantees in this setting is challenging. In this work, we derive a reconstruction algorithm with theoretical guarantees using Neighbor-Joining (NJ) on distances that are moment-matched to estimate the true tree distances. We develop a series of tools to analyze this algorithm and prove its theoretical guarantees. Empirically, we show on both simulated lineage tracing data and on real data from a mouse model of lung cancer the improved performance of our method as compared to the traditional use of NJ.

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BT - Research in Computational Molecular Biology - 29th International Conference, RECOMB 2025, Proceedings

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Prillo S, An K, Wu W, Kristanto I, Jones MG, Song YS et al. Tree Reconstruction Guarantees from CRISPR-Cas9 Lineage Tracing Data Using Neighbor-Joining. In Sankararaman S, editor, Research in Computational Molecular Biology - 29th International Conference, RECOMB 2025, Proceedings. Springer Science and Business Media B.V. 2025. p. 376-380. (Lecture Notes in Computer Science). doi: 10.1007/978-3-031-90252-9_43

Tree Reconstruction Guarantees from CRISPR-Cas9 Lineage Tracing Data Using Neighbor-Joining

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