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Activity Number: 252
Type: Contributed
Date/Time: Monday, August 1, 2016 : 2:00 PM to 3:50 PM
Sponsor: Section on Statistics in Genomics and Genetics
Abstract #319987 View Presentation
Title: Assessing Intra-Tumor Heterogeneity and Tracking Longitudinal and Spatial Clonal Evolution by Next-Generation Sequencing
Author(s): Yuchao Jiang* and Yu Qiu and Andy J. Minn and Nancy Zhang
Companies: University of Pennsylvania and University of Pennsylvania and University of Pennsylvania and University of Pennsylvania
Keywords: intra-tumor heterogeneity ; cancer phylogeny ; clonal deconvolution ; cancer genomics
Abstract:

Cancer is driven by genetic and epigenetic alterations that follows Darwinian evolution. Recently, there have been increasing efforts to sequence the tumor from the same patient at multiple time points and/or from multiple spatially separated resections. We propose a method, Canopy, for reconstructing the tumor's subclonal phylogeny using both copy number alterations (CNAs) and single nucleotide alterations (SNAs) from sample(s) derived from a single patient. Canopy provides a mathematical framework that enumerates all possible CNA-SNA phases and gives confidence assessments of all possible phylogenetic configurations. On a whole-exome study of a transplantable metastasis model derived from cell line MDA-MB-231, Canopy successfully deconvolutes the mixed-cell sublines, using the single-cell sublines as ground truth. On a whole-genome sequencing dataset of a breast cancer tumor and its metastatic xenografts, Canopy's inferred clonal phylogeny is confirmed by single-cell sequencing. Through simulations, we explore the effects of various parameters on deconvolution accuracy, and evaluate performance with comparison against existing methods.


Authors who are presenting talks have a * after their name.

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