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Optimizing Cancer Genome Sequencing and Analysis
2015
Cell Systems
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Additional targeted sequencing provided over 10,000× coverage and ddPCR assays provided up to ~250,000× sampling of selected sites. ...
We demonstrate that current sequencing paradigms are inadequate for tumors that are impure, aneuploid or clonally heterogeneous. ...
Ley from the NCI (PO1CA101937) and to Richard K. Wilson from the NHGRI (U54HG003079). ...
doi:10.1016/j.cels.2015.08.015
pmid:26645048
pmcid:PMC4669575
fatcat:3sm5sn4tfncjrhmzdjrmucvqxi
Computational approaches for inferring tumor evolution from single-cell genomic data
2018
Current Opinion in Systems Biology
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Genomic heterogeneity in tumors results from mutations and selection of high-fitness single cells, the operational components of evolution. ...
Precise knowledge about mutational heterogeneity and evolutionary trajectory of a tumor can provide useful insights into predicting cancer progression and designing personalized treatment. ...
Figure 3 Tumor 3 phylogeny inference from single-cell sequencing data. (a) Illustration of a heterogeneous tumor tissue that evolved according to the clonal expansion represented in (b). ...
doi:10.1016/j.coisb.2017.11.008
fatcat:ynw5xltnvndghbajgpmhnjpmhy
TITAN: inference of copy number architectures in clonal cell populations from tumor whole-genome sequence data
2014
Genome Research
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Finally, we experimentally validated subclonal predictions using fluorescence in situ hybridization (FISH) and single-cell sequencing from an ovarian cancer patient sample, thereby recapitulating the key ...
We evaluate TITAN on idealized mixtures, simulating clonal populations from whole-genome sequences taken from genomically heterogeneous ovarian tumor sites collected from the same patient. ...
of TITAN predictions using single-cell sequencing confirm the presence of multiple tumor populations We further validated the CNA predictions from DG1136g using single-cell sequencing of targeted positions ...
doi:10.1101/gr.180281.114
pmid:25060187
pmcid:PMC4216928
fatcat:77ddt6of3vbqrizara7ckukc6e
Sensitivity to sequencing depth in single-cell cancer genomics
2018
Genome Medicine
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structural and driver mutations, genotyping accuracy, clonal inference 10 and phylogenetic reconstruction, using recent tools specifically designed for 11 single-cell data. 12 Results: Altogether, our ...
of clonal genotypes or 15 the estimation of phylogenies from single tumor cells. 16 Conclusions: We demonstrate that sequencing many individual tumor cells at a 17 modest depth represents an effective ...
OncoNEM: inferring tumor evolution from single-cell 418 sequencing data. Genome Biol. 2016;17: 69. 419 25. Zafar H, Tzen A, Navin N, Chen K, Nakhleh L. ...
doi:10.1186/s13073-018-0537-2
pmid:29661213
pmcid:PMC5901877
fatcat:paq4ckb67ngtfgsk7oqzcmkctm
Accucopy: accurate and fast inference of allele-specific copy number alterations from low-coverage low-purity tumor sequencing data
2021
BMC Bioinformatics
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Detecting genomic alterations from the shallow-sequencing data of a low-purity tumor sample remains a challenging task. ...
Conclusions We describe Accucopy, a method that can predict both TCNs and ASCNs from low-coverage low-purity tumor sequencing data. ...
infer CNAs from these tumor sequencing data [6] [7] [8] [9] [10] but few automated and efficient methods exist to infer CNAs by shallow-sequencing low-purity tumor samples. ...
doi:10.1186/s12859-020-03924-5
pmid:33451280
fatcat:qle7ra6tejgzhdnxsjsftb7xpq
Current Progresses of Single Cell DNA Sequencing in Breast Cancer Research
2017
International Journal of Biological Sciences
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Clonal evolution theory recapitulates that a tumor initially arises from a single cell, which then undergoes clonal expansion to a population of cancer cells. ...
In recent years, single cell sequencing (SCS) technology developed rapidly, providing a powerful new way to better understand the heterogeneity, which may lay foundations to some new strategies for breast ...
using single nucleus sequencing with low coverage (~6%), revealing three different subclones that might represent sequential clonal expansion. ...
doi:10.7150/ijbs.19627
pmid:28924377
pmcid:PMC5599901
fatcat:67yz3qyb2jc37gwitlxshltwq4
Conifer: clonal tree inference for tumor heterogeneity with single-cell and bulk sequencing data
2021
BMC Bioinformatics
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Result In this study, a new method called Conifer (ClONal tree Inference For hEterogeneity of tumoR) is proposed which combines aggregated variant allele frequency from bulk sequencing data with branching ...
However, the temporal order of mutations may be determined with ambiguities using only single-cell data, while variant allele frequencies from bulk sequencing data can provide beneficial information for ...
B-SCITE [21] is the first computational approach that infers tumor phylogeny from combined single-cell and bulk sequencing data. ...
doi:10.1186/s12859-021-04338-7
pmid:34461827
fatcat:hgrod6swxvggfftjjj6iedvh6q
Sensitivity to sequencing depth in single-cell cancer genomics
[article]
2017
bioRxiv
pre-print
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structural and driver mutations, genotyping accuracy, clonal inference and phylogenetic reconstruction, using recent tools specifically designed for single-cell data. ...
of clonal genotypes or the estimation of phylogenies from single tumor cells. ...
OncoNEM: inferring tumor evolution from single-cell 418 sequencing data. Genome Biol. 2016;17: 69. 419 25. Zafar H, Tzen A, Navin N, Chen K, Nakhleh L. ...
doi:10.1101/213744
fatcat:5jibl2rejrh3npwsrq6eqgyfbe
Advances for studying clonal evolution in cancer
2013
Cancer Letters
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New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape ...
Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. ...
Acknowledgments The authors are supported by grants from the NIH (U01HG006517, U54HG003079, R01HG005690, R01DK081592, and R01DK087960). ...
doi:10.1016/j.canlet.2012.12.028
pmid:23353056
pmcid:PMC3783624
fatcat:u3723hwp4bayrf3njn4rp57piu
Parameter, noise, and tree topology effects in tumor phylogeny inference
2019
BMC Medical Genomics
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While a number of methods have been proposed to reconstruct the evolutionary history of a tumor from DNA sequencing data, it is not clear how aspects of the sequencing data and tumor itself affect these ...
Accurate inference of the evolutionary history of a tumor has important implications for understanding and potentially treating the disease. ...
Many recent computational methods have been developed to infer tumor phylogenetic trees using multi-sample bulk sequencing data. ...
doi:10.1186/s12920-019-0626-0
pmid:31865909
pmcid:PMC6927103
fatcat:p5nomzes5jdwhkvr3b5tiawq34
Inferring Clonal Composition from Multiple Sections of a Breast Cancer
2014
PLoS Computational Biology
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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 ...
We propose a generative model for NGS data derived from multiple subsections of a single tumor, and we describe an expectation-maximization procedure for estimating the clonal genotypes and relative frequencies ...
We collect, from several physical subsections of the tumor, shotgun sequencing reads. We also collect sequencing data from a non-tumor subsection from the same patient. ...
doi:10.1371/journal.pcbi.1003703
pmid:25010360
pmcid:PMC4091710
fatcat:c76nicayvnfsviybege3yxy2i4
Clonal Architecture of Secondary Acute Myeloid Leukemia Defined by Single-Cell Sequencing
2014
PLoS Genetics
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Next-generation sequencing has been used to infer the clonality of heterogeneous tumor samples. ...
cells from three subjects diagnosed with secondary acute myeloid leukemia, each of whom had been previously characterized by whole genome sequencing of unfractionated tumor samples. ...
In addition to multi-sampling strategies, we and others have reported clonal inference from deep sequencing of individual tumor samples [1, [13] [14] [15] . ...
doi:10.1371/journal.pgen.1004462
pmid:25010716
pmcid:PMC4091781
fatcat:xodczvuzrjhy5met3tu6yzycdq
Tracing the evolution of aneuploid cancers by multiregional sequencing with CRUST
2021
Briefings in Bioinformatics
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Using published and simulated tumor sequences, we reliably segregated clonal/subclonal variants even at a low sequencing depth (~50×). ...
Absent à priori copy number data, it renders in silico copy number estimations from bulk sequences. ...
A special thanks to Chris Miller and Malachi Griffith for their assistance in procuring data from community resources (dbGaP: phs000159). ...
doi:10.1093/bib/bbab292
pmid:34343239
pmcid:PMC8981300
fatcat:vgjspskpu5aj3and6dr4ynsboe
Characterizing the allele- and haplotype-specific copy number landscape of cancer genomes at single-cell resolution with CHISEL
[article]
2019
bioRxiv
pre-print
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These technologies provide the opportunity to characterize genomic heterogeneity at single-cell resolution, but their extremely low sequencing coverage (<0.05X per cell) has thus far restricted their use ...
We applied CHISEL to 10 single-cell sequencing datasets from 2 breast cancer patients, each dataset containing ~2000 cells. ...
Acknowledgments We thank Lance Hepler and Karthik Ganapathy from 10X Genomics for providing additional data for our study, for providing access to the published data of the total copy number analysis, ...
doi:10.1101/837195
fatcat:rrsb2qplvnb4tjlonct3dol5gy
Intratumor Heterogeneity: Novel Approaches for Resolving Genomic Architecture and Clonal Evolution
2017
Molecular Cancer Research
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This review focuses on novel approaches to mitigate these challenges using bulk tumor, liquid biopsies, single-cell analysis, and deep sequencing techniques. ...
and clonal selection. ...
Recurrent mutaƟons A C T A C T G A C T A C T G
Inferring Clonal Evolution from Deep Sequencing Data As the sampling depth of sequencing techniques increases, so too will the multiplicity of genomic changes ...
doi:10.1158/1541-7786.mcr-17-0070
pmid:28596419
fatcat:nyfrmxfskzfj7pdhwjufjdmpdm
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