Apr 1, 2020

PhyDOSE: Design of Follow-up Single-cell Sequencing Experiments of Tumors

BioRxiv : the Preprint Server for Biology
L. WeberMohammed El-Kebir

Abstract

The combination of bulk and single-cell DNA sequencing data of the same tumor enables the inference of high-fidelity phylogenies that form the input to many important downstream analyses in cancer genomics. While many studies simultaneously perform bulk and single-cell sequencing, some studies have analyzed initial bulk data to identify which mutations to target in a follow-up single-cell sequencing experiment, thereby decreasing cost. Bulk data provide an additional untapped source of valuable information, composed of candidate phylogenies and associated clonal prevalences. Here, we introduce PhyDOSE, a method that uses this information to strategically optimize the design of follow-up single cell experiments. Underpinning our method is the observation that only a small number of clones uniquely distinguish one candidate tree from all other trees. We incorporate distinguishing features into a probabilistic model that infers the number of cells to sequence so as to confidently reconstruct the phylogeny of the tumor. We validate PhyDOSE using simulations and a retrospective analysis of a leukemia patient, concluding that PhyDOSE's computed number of cells resolves tree ambiguity even in the presence of typical single-cell sequen...Continue Reading

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Mentioned in this Paper

Commiphora capensis
Carios capensis
Platypleura capensis
Positioning Attribute
Chrysitrix capensis
CFC1 gene
Chestnut Animal Structure
HLB 817
Crepipatella capensis
Genes

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