![]() ![]() a The workflow of a lineage tracing experiment. Cassiopeia and its benchmarking resources are publicly available at Keywords:ĬRISPR Lineage tracing Single cell scRNA-seq.Ī generalized approach to lineage tracing and lineage reconstruction. Together, these should broadly enable large-scale mammalian lineage tracing efforts. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. First, we introduce Cassiopeia-a suite of scalable maximum parsimony approaches for tree reconstruction. ![]() However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. 14 Chan Zuckerberg Biohub Investigator, San Francisco, CA, USA. 13 Ragon Institute of Massachusetts General Hospital - MIT and Harvard, Cambridge, MA, USA. 12 Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California Berkeley, Berkeley, CA, USA. 11 Center for Computational Biology, University of California Berkeley, Berkeley, CA, USA. 10 Center for RNA Systems Biology, University of California San Francisco, San Francisco, CA, USA. 9 Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA. 8 Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA, USA.7 University of California, San Francisco, Department of Microbiology and Immunology, San Francisco, California, USA.6 Center for RNA Systems Biology, University of California San Francisco, San Francisco, CA, USA.5 Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California Berkeley, Berkeley, CA, USA.4 Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA. ![]() ![]() 3 Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA, USA.2 Center for Computational Biology, University of California Berkeley, Berkeley, CA, USA.1 Biological and Medical Informatics Graduate Program, University of California San Francisco, San Francisco, CA, USA. ![]()
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