PATH is an R package for analyzing multi-modal single-cell phylogenies, developed and maintained by the Landau Lab at the New York Genome Center & Weill Cornell Medicine.
For more information and background, as well as technical details, see our manuscript Defining ancestry, heritability and plasticity of cellular phenotypes in somatic evolution.
install.packages("devtools")
devtools::install_github("landau-lab/PATH")PATH -- Phylogenetic Analysis of Trait Heritability -- is an analytical framework for quantifying cell state heritability versus plasticity and inferring cell state transition and proliferation dynamics, in the context of somatic evolution, by using phenotypically annotated single-cell lineage trees or phylogenies.
Single-cell phylogenies represent the ancestral relatedness of individual cells, and if annotated with additional measurements, such as transcriptional state (e.g., from scRNAseq), present a unique opportunity to study somatic evolutionary dynamics. PATH's analytical tools can be applied to these types of data to,
- (i) quantify cell state heritability versus plasticity by measuring phylogenetic correlations,
- (ii) infer phenotypic transition dynamics, and further,
- (iii) identify heritable gene modules or pathways.
For examples of how to apply PATH, see the vignettes listed below.
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PATH analysis of idealized phylogenies demonstates how to use PATH to measure phylogenetic correlations and how to infer cell state transition dynamics on simulated idealized phylogenies. Idealized phylogenies represent a simplified situation useful for understanding how PATH works.
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PATH analysis of somatic evolution demonstates how to use PATH to measure phylogenetic correlations and how to infer cell state transition dynamics on phylogenies simulated by a sampled somatic evolutionary process. These phylogenies should more closely resemble those derived from experiment.
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PATH analysis of cancer demonstrates how to apply PATH to an experimentally derived single-cell phylogeny with matching scRNAseq. Specifically, in this vignette, PATH is applied to a patient-derived glioblastoma phylogeny, to measure transcriptional cell state heritability versus plasticity, to infer cell state transition dynamics, and to discover heritable transcriptional modules in an unbiased fashion.
This interactive PATH Simulator web app can also be used for simple demonstrations.