Abstract
Copy number alterations are driving forces of tumour development and the emergence of intra-tumour heterogeneity. A comprehensive picture of these genomic aberrations is therefore essential for the development of personalised and precise cancer diagnostics and therapies. Single-cell sequencing offers the highest resolution for copy number profiling down to the level of individual cells. Recent high-throughput protocols allow for the processing of hundreds of cells through shallow whole-genome DNA sequencing. The resulting low read-depth data poses substantial statistical and computational challenges to the identification of copy number alterations. We developed SCICoNE, a statistical model and MCMC algorithm tailored to single-cell copy number profiling from shallow whole-genome DNA sequencing data. SCICoNE reconstructs the history of copy number events in the tumour and uses these evolutionary relationships to identify the copy number profiles of the individual cells. We show the accuracy of this approach in evaluations on simulated data and demonstrate its practicability in applications to a xenograft breast cancer sample. Show more
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https://doi.org/10.3929/ethz-b-000528553Publication status
publishedExternal links
Journal / series
bioRxivPublisher
Cold Spring Harbor LaboratoryOrganisational unit
03790 - Beerenwinkel, Niko / Beerenwinkel, Niko
Funding
609883 - Mechanisms of Evasive Resistance in Liver Cancer (EC)
179518 - Using single-cell sequencing data to analyse tumour evolution (SNF)
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