2019
DOI: 10.1101/595215
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Estimation of cell lineage trees by maximum-likelihood phylogenetics

Abstract: 9CRISPR technology has enabled large-scale cell lineage tracing for complex multicellular organisms 10 by mutating synthetic genomic barcodes during organismal development. However, these sophisti-11 cated biological tools currently use ad-hoc and outmoded computational methods to reconstruct 12 the cell lineage tree from the mutated barcodes. Because these methods are agnostic to the 13 biological mechanism, they are unable to take full advantage of the data's structure. We propose a 14 statistical model for … Show more

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Cited by 10 publications
(9 citation statements)
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“…While maximum parsimony methods are attractive due to their non-parametric nature, future studies may build on our work here by developing more powerful approaches for integrating prior mutation rates into maximum likelihood [20,21] or Bayesian inference [51] frameworks, perhaps relying on recent literature that seeks to predict indel formation probabilities [40][41][42]. Future work in this space may also focus on using maximum parsimony solutions to further refine solutions in an effort to resolve branch length as with GAPML [52] or with paired transcriptomic observations [53]. Second, there exists a promising opportunity in developing new approaches for better handling of missing data.…”
Section: Discussionmentioning
confidence: 99%
“…While maximum parsimony methods are attractive due to their non-parametric nature, future studies may build on our work here by developing more powerful approaches for integrating prior mutation rates into maximum likelihood [20,21] or Bayesian inference [51] frameworks, perhaps relying on recent literature that seeks to predict indel formation probabilities [40][41][42]. Future work in this space may also focus on using maximum parsimony solutions to further refine solutions in an effort to resolve branch length as with GAPML [52] or with paired transcriptomic observations [53]. Second, there exists a promising opportunity in developing new approaches for better handling of missing data.…”
Section: Discussionmentioning
confidence: 99%
“…At the end of the lineage tracing experiment, the indel alleles are collected from individual cells by sequencing and paired with single-cell expression profiles of the cell state (22,23). Then, as in retrospective tracing approaches, computational approaches (29)(30)(31)(32)(33)(34) can reconstruct a phylogenetic tree that best models subclonal cellular relationships (e.g., by maximum-parsimony) from the observed shared or distinguishing alleles. Thus far, Cas9-enabled tracing has been successfully applied to study the cellular progenitor landscape in early mammalian embryogenesis (23,35), hematopoiesis (36), and neural development in zebrafish (22).…”
mentioning
confidence: 99%
“…Finally, due to the random nature of these mutations, it is impossible to utilize them to reconstruct a consensus lineage tree by combining data from repeated experiments of the same species, in contrast to most phylogenetic studies 33 . While very recently, computational methods that address some of these challenges are being developed 21,34,35 , they still rely only on mutation information. ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi ffi Àlog ðp valueÞ p , higher value means more significant) for GO terms for invariant clusters.…”
Section: Discussionmentioning
confidence: 99%