Tracing the evolution of aneuploid cancers by multiregional sequencing with CRUST
(2021) In Briefings in Bioinformatics 22(6).- Abstract
Clonal deconvolution of mutational landscapes is crucial to understand the evolutionary dynamics of cancer. Two limiting factors for clonal deconvolution that have remained unresolved are variation in purity and chromosomal copy number across different samples of the same tumor. We developed a semi-supervised algorithm that tracks variant calls through multi-sample spatiotemporal tumor data. While normalizing allele frequencies based on purity, it also adjusts for copy number changes at clonal deconvolution. Absent à priori copy number data, it renders in silico copy number estimations from bulk sequences. Using published and simulated tumor sequences, we reliably segregated clonal/subclonal variants even at a low sequencing depth... (More)
Clonal deconvolution of mutational landscapes is crucial to understand the evolutionary dynamics of cancer. Two limiting factors for clonal deconvolution that have remained unresolved are variation in purity and chromosomal copy number across different samples of the same tumor. We developed a semi-supervised algorithm that tracks variant calls through multi-sample spatiotemporal tumor data. While normalizing allele frequencies based on purity, it also adjusts for copy number changes at clonal deconvolution. Absent à priori copy number data, it renders in silico copy number estimations from bulk sequences. Using published and simulated tumor sequences, we reliably segregated clonal/subclonal variants even at a low sequencing depth (~50×). Given at least one pure tumor sample (>70% purity), we could normalize and deconvolve paired samples down to a purity of 40%. This renders a reliable clonal reconstruction well adapted to multi-regionally sampled solid tumors, which are often aneuploid and contaminated by non-cancer cells.
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- author
- Chattopadhyay, Subhayan LU ; Karlsson, Jenny LU ; Valind, Anders LU ; Andersson, Natalie LU and Gisselsson, David LU
- organization
- publishing date
- 2021-08-03
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Briefings in Bioinformatics
- volume
- 22
- issue
- 6
- publisher
- Oxford University Press
- external identifiers
-
- scopus:85121949131
- pmid:34343239
- ISSN
- 1477-4054
- DOI
- 10.1093/bib/bbab292
- language
- English
- LU publication?
- yes
- id
- bac74b02-ab1d-49c8-b751-e52a07fb1e28
- date added to LUP
- 2021-09-08 11:46:34
- date last changed
- 2024-08-08 14:37:18
@article{bac74b02-ab1d-49c8-b751-e52a07fb1e28, abstract = {{<p>Clonal deconvolution of mutational landscapes is crucial to understand the evolutionary dynamics of cancer. Two limiting factors for clonal deconvolution that have remained unresolved are variation in purity and chromosomal copy number across different samples of the same tumor. We developed a semi-supervised algorithm that tracks variant calls through multi-sample spatiotemporal tumor data. While normalizing allele frequencies based on purity, it also adjusts for copy number changes at clonal deconvolution. Absent à priori copy number data, it renders in silico copy number estimations from bulk sequences. Using published and simulated tumor sequences, we reliably segregated clonal/subclonal variants even at a low sequencing depth (~50×). Given at least one pure tumor sample (>70% purity), we could normalize and deconvolve paired samples down to a purity of 40%. This renders a reliable clonal reconstruction well adapted to multi-regionally sampled solid tumors, which are often aneuploid and contaminated by non-cancer cells.</p>}}, author = {{Chattopadhyay, Subhayan and Karlsson, Jenny and Valind, Anders and Andersson, Natalie and Gisselsson, David}}, issn = {{1477-4054}}, language = {{eng}}, month = {{08}}, number = {{6}}, publisher = {{Oxford University Press}}, series = {{Briefings in Bioinformatics}}, title = {{Tracing the evolution of aneuploid cancers by multiregional sequencing with CRUST}}, url = {{http://dx.doi.org/10.1093/bib/bbab292}}, doi = {{10.1093/bib/bbab292}}, volume = {{22}}, year = {{2021}}, }