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Single-cell tumor phylogeny inference with copy-number constrained mutation losses [article]

Gryte Satas, Simone Zaccaria, Geoffrey Mon, Benjamin J. Raphael
2019 bioRxiv   pre-print
a novel loss-supported evolutionary model, a generalization of the infinite sites and Dollo models, that constrains mutation losses to loci with evidence of a decrease in copy number.  ...  We design a new algorithm, Single-Cell Algorithm for Reconstructing the Loss-supported Evolution of Tumors (Scarlet), that infers phylogenies from single-cell tumor sequencing data using the loss-supported  ...  for single-cell phylogeny inference that allow loss of mutations.  ... 
doi:10.1101/840355 fatcat:ijprxow54ncl7ohizqumvxfxy4

SCARLET: Single-Cell Tumor Phylogeny Inference with Copy-Number Constrained Mutation Losses

Gryte Satas, Simone Zaccaria, Geoffrey Mon, Benjamin J. Raphael
2020 Cell Systems  
Here, we introduce SCARLET, an algorithm that infers tumor phylogenies from single-cell DNA sequencing data while accounting for both CNA-driven loss of SNVs and sequencing errors.  ...  Prominent methods to construct phylogenies from single-cell sequencing data use single-nucleotide variants (SNVs) as markers but fail to adequately account for copy-number aberrations (CNAs), which can  ...  In contrast, SCARLET infers a loss-supported phylogeny that has three mutation losses, with each loss supported by a copy-number change at the locus.  ... 
doi:10.1016/j.cels.2020.04.001 pmid:32864481 pmcid:PMC7451135 fatcat:kux5tvhagnfone3qte37f24jwm

Single-Cell Tumor Phylogeny Inference with Copy-Number Constrained Mutation Losses [chapter]

Gryte Satas, Simone Zaccaria, Geoffrey Mon, Benjamin J. Raphael
2020 Lecture Notes in Computer Science  
However, most solid tumors contain copy-number aberrations (CNAs) which can overlap loci containing SNVs.  ...  Motivation: Single-cell DNA sequencing enables the measurement of somatic mutations in individual tumor cells, and provides data to reconstruct the evolutionary history of the tumor.  ...  Scarlet substantially improves single-cell phylogeny inference in tumors with CNAs, yielding new insights into the analysis of tumor evolution.  ... 
doi:10.1007/978-3-030-45257-5_35 fatcat:qx3qtm3qbfaqld6doneqxnc24y

Reconstructing subclonal composition and evolution from whole genome sequencing of tumors [article]

Amit G. Deshwar, Shankar Vembu, Christina K. Yung, Gun Ho Jang, Lincoln Stein, Quaid Morris
2014 bioRxiv   pre-print
collectively called simple somatic mutations (SSMs) ? as well as larger structural changes that result in copy number variations (CNVs).  ...  These so-called subclonal populations are defined by distinct somatic mutations that include point mutations such as single nucleotide variants and small indels ?  ...  C m copies of the SSM and cells with the SSM but not the CNV only have one mutated copy.  ... 
doi:10.1101/006692 fatcat:n5urzmr4mfgbto5mpld3g2rdae

Deconvolution and phylogeny inference of structural variations in tumor genomic samples

Jesse Eaton, Jingyi Wang, Russell Schwartz
2018 Bioinformatics  
One crucial question in that regard is how to handle inference of structural variations (SVs), which are a major mechanism of evolution in cancers but have been largely neglected in tumor phylogenetics  ...  We demonstrate the approach to be efficient and accurate for realistic scenarios of SV mutation on simulated data.  ...  Acknowledgement The authors thank Ashok Rajaraman and Jian Ma for helpful discussions and assistance with Weaver.  ... 
doi:10.1093/bioinformatics/bty270 pmid:29950001 pmcid:PMC6022719 fatcat:bzknk2ermnbunokatq5mszaole

Deconvolution and phylogeny inference of structural variations in tumor genomic samples [article]

Jesse Eaton, Jingyi Wang, Russell Schwartz
2018 bioRxiv   pre-print
Application to breast cancer genomic data from The Cancer Genome Atlas (TCGA) shows it to be practical and effective at reconstructing features of SV-driven evolution in single tumors.  ...  We demonstrate the approach to be efficient and accurate for realistic scenarios of SV mutation on simulated data.  ...  Acknowledgments: We thank Ashok Rajaraman and Jian Ma for helpful discussions and assistance with Weaver. Portions of this work have been funded by the U.S.  ... 
doi:10.1101/257014 fatcat:gelbihcb2nglhhlrkt2fwgd3pa

A Big Bang model of human colorectal tumor growth

Andrea Sottoriva, Haeyoun Kang, Zhicheng Ma, Trevor A Graham, Matthew P Salomon, Junsong Zhao, Paul Marjoram, Kimberly Siegmund, Michael F Press, Darryl Shibata, Christina Curtis
2015 Nature Genetics  
Moreover, some tumors appear born-to-be-bad, with sub-clone mixing indicative of early malignant potential.  ...  Here we present and validate a "Big Bang" model, whereby tumors grow predominantly as a single expansion producing numerous intermixed sub-clones that are not subject to stringent selection, and where  ...  Acknowledgments The project described was supported in part by an award to C.C. from the V Foundation for Cancer Research and by award numbers P30CA014089, R21CA149990 and R21CA151139 from the National  ... 
doi:10.1038/ng.3214 pmid:25665006 pmcid:PMC4575589 fatcat:2oxig2iuhbabhel2ky24mw4pxy

PhyloWGS: Reconstructing subclonal composition and evolution from whole-genome sequencing of tumors

Amit G Deshwar, Shankar Vembu, Christina K Yung, Gun Jang, Lincoln Stein, Quaid Morris
2015 Genome Biology  
Tumors often contain multiple subpopulations of cancerous cells defined by distinct somatic mutations.  ...  We introduce a principled phylogenic correction for VAFs in loci affected by copy number alterations and we show that this correction greatly improves subclonal reconstruction compared to existing methods  ...  In this case, cells with the CNV contain C m copies of the SSM, and cells with the SSM but not the CNV have only one mutated copy.  ... 
doi:10.1186/s13059-015-0602-8 pmid:25786235 fatcat:7qr2yg2rebeabeerwemid6zpuq

Reconstructing subclonal composition and evolution from whole genome sequencing of tumors [article]

Amit G. Deshwar, Shankar Vembu, Christina K. Yung, Gun Ho Jang, Lincoln Stein, Quaid Morris
2015 arXiv   pre-print
Tumors often contain multiple subpopulations of cancerous cells defined by distinct somatic mutations.  ...  We introduce a principled phylogenic correction for VAFs in loci affected by copy number alterations and we show that this correction greatly improves subclonal reconstruction compared to existing methods  ...  In this case, cells with the CNV contain C m copies of the SSM and cells with the SSM but not the CNV only have one mutated copy.  ... 
arXiv:1406.7250v3 fatcat:c2erfn5bcfdkjaov2ilix5zr2q

Tumor Copy Number Deconvolution Integrating Bulk and Single-Cell Sequencing Data: Supplementary Materials [article]

Haoyun Lei, Bochuan Lyu, E. Michael Gertz, Alejandro A. Schaeffer, Xulian Shi, Kui Wu, Guibo Li, Liquin Xu, Yong Hu, Michael Dean, Russell Schwartz
2019 bioRxiv   pre-print
We have developed strategies for deconvolution and tumor phylogenetics combining limited amounts of bulk and single-cell data to gain some advantages of single-cell resolution with much lower cost, with  ...  specific focus on deconvolving genomic copy number data.  ...  In each tree, nodes 0 -5 are inferred cells, nodes 6 -11 are observed cells, and node 12 is the diploid root. copy number profiles and their proportions in single-or multi-sample tumor genomic data.  ... 
doi:10.1101/519892 fatcat:radxvlu7hndk3lwepn2a22xxkq

doubletD: detecting doublets in single-cell DNA sequencing data

Leah L Weber, Palash Sashittal, Mohammed El-Kebir
2021 Bioinformatics  
where two or more cells are mistaken for a single cell.  ...  Not only do doublets confound downstream analyses, but the increase in doublet rate is also a major bottleneck preventing higher throughput with current single-cell technologies.  ...  Using that each mutation locus has copy number 2 in a single cell and allowing any number of copies to drop out, we have Table S1 lists all values of Pðy i;j jx i;j ; z i Þ for varying ðx i;j ; z i Þ  ... 
doi:10.1093/bioinformatics/btab266 pmid:34252961 fatcat:nfclh4yd3vd5hmnck2u72hmue4

Inferring tumor evolution from longitudinal samples [article]

Matthew A. Myers, Gryte Satas, Benjamin J. Raphael
2019 bioRxiv   pre-print
On real data, where there is often considerable uncertainty in the clonal composition of a sample, longitudinal constraints yield more parsimonious phylogenies with fewer tumor clones per sample.  ...  However, none of the existing algorithms that infer clonal composition and phylogeny using several bulk tumor samples from the same patient integrate the information that these samples were obtained from  ...  First, we focused on SNVs in diploid regions, ignoring copy number aberrations which complicate tumor phylogeny reconstruction [2, 4, 12] .  ... 
doi:10.1101/526814 fatcat:s5cmb76jfza6bk3dri5tsfbcky

Inferring Clonal Composition from Multiple Sections of a Breast Cancer

Habil Zare, Junfeng Wang, Alex Hu, Kris Weber, Josh Smith, Debbie Nickerson, ChaoZhong Song, Daniela Witten, C. Anthony Blau, William Stafford Noble, Amos Tanay
2014 PLoS Computational Biology  
Applying this method to larger numbers of tumors should cast light on the clonal evolution of cancers in space and time.  ...  Mutation counts and frequencies resulting from next-generation sequencing (NGS) potentially reflect a tumor's clonal composition; however, deconvolving NGS data to infer a tumor's clonal structure presents  ...  Hence, these mutation frequencies are consistent with the inferred phylogeny.  ... 
doi:10.1371/journal.pcbi.1003703 pmid:25010360 pmcid:PMC4091710 fatcat:c76nicayvnfsviybege3yxy2i4

Does relaxing the infinite sites assumption give better tumor phylogenies? An ILP-based comparative approach [article]

Paola Bonizzoni, Simone Ciccolella, Gianluca Della Vedova, Mauricio Soto
2017 bioRxiv   pre-print
Some recent results gives a strong evidence that recurrent and back mutations are present in the evolutionary history of tumors, thus showing that more general models then the Perfect Phylogeny are required  ...  An experimental analysis shows the usefulness of allowing mutation losses, by studying some real and simulated datasets where our ILP approach provides a better interpretation than the one obtained under  ...  Cancer is an uncontrolled evolutionary process of somatic mutations of tumor cells from a single founder cell [13] creating a diverse set of subpopulations [8, 22, 31] , each originated from a single  ... 
doi:10.1101/227801 fatcat:ivswri6qlbhfxdcncngl7nu4y4

A population genetics perspective on the determinants of intra-tumor heterogeneity

Zheng Hu, Ruping Sun, Christina Curtis
2017 Biochimica et Biophysica Acta. CR. Reviews on Cancer  
Although these processes cannot be directly observed, the resultant spatiotemporal patterns of genetic variation amongst tumor cells encode their evolutionary histories.  ...  Such intra-tumor heterogeneity is pervasive not only at the genomic level, but also at the transcriptomic, phenotypic, and cellular levels.  ...  This approach takes as input integer copy number profiles and B-allele frequencies and has been used to reconstruct tumor phylogenies from multi-region copy number profiles [21, 163] .  ... 
doi:10.1016/j.bbcan.2017.03.001 pmid:28274726 pmcid:PMC5623098 fatcat:ome6ulz2lzejrgkzzj2krwf4de
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