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LAML-Pro: joint maximum likelihood inference of cell genotypes and cell lineage trees
Gillian Chu1, Henri Schmidt1, Benjamin J Raphael1
1Department of Computer Science, Princeton University, Princeton, NJ 08540, United States.
Bioinformatics (Oxford, England)
|July 7, 2026
Summary
This study introduces LAML-Pro, a new algorithm that accurately reconstructs cell lineage trees by simultaneously inferring cell genotypes and tree structures. LAML-Pro corrects errors in genotype data, improving lineage tree accuracy for dynamic lineage tracing applications.
Area of Science:
- Computational Biology
- Genetics
- Bioinformatics
Background:
- Dynamic lineage tracing uses genome editing to create heritable mutations for reconstructing cell lineages.
- Current methods separate genotype identification from lineage tree inference, leading to inaccuracies due to genotyping errors (≈25%-50% in imaging).
Purpose of the Study:
- To develop a computational method that jointly infers cell genotypes and lineage trees to overcome limitations of current two-step approaches.
- To improve the accuracy and robustness of cell lineage reconstruction from dynamic lineage tracing data.
Main Methods:
- Introduced Lineage Analysis via Maximum Likelihood with Probabilistic Observations (LAML-Pro), based on the Probabilistic Mixed-type Missing Observation (PMMO) model.
- Developed a joint inference algorithm that accounts for both genome editing and genotype observation processes.
- Leveraged model sparsity for efficient computation, enabling analysis of thousands of cells rapidly.
Main Results:
- LAML-Pro corrects genotype errors and infers more accurate cell lineage trees compared to existing methods on simulated data.
- Applied to imaging-based lineage tracing data, LAML-Pro reduced genotype errors fivefold.
- Generated more spatially coherent lineage trees, demonstrating improved performance in real-world applications.
Conclusions:
- LAML-Pro offers a significant advancement in cell lineage reconstruction by integrating genotype inference and tree building.
- The algorithm enhances the reliability of dynamic lineage tracing, particularly in systems prone to genotyping errors.
- LAML-Pro provides a faster and more accurate computational tool for understanding cellular development and dynamics.
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