Reconstruction of clonal trees and tumor composition from multi-sample sequencing data

Bioinformatics, Journal Year: 2015, Volume and Issue: 31(12), P. i62 - i70

Published: June 10, 2015

DNA sequencing of multiple samples from the same tumor provides data to analyze process clonal evolution in population cells that give rise a tumor. We formalize problem reconstructing using single-nucleotide mutations as variant allele frequency (VAF) factorization problem. derive combinatorial characterization solutions this and show is NP-complete. an integer linear programming solution VAF case error-free extend real with probabilistic model for errors. The resulting AncesTree algorithm better able identify ancestral relationships between individual than existing approaches, particularly ultra-deep when high read counts yield confidence VAFs. An implementation available at: http://compbio.cs.brown.edu/software.

Language: Английский

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Assessing intratumor heterogeneity and tracking longitudinal and spatial clonal evolutionary history by next-generation sequencing

Proceedings of the National Academy of Sciences, Journal Year: 2016, Volume and Issue: 113(37)

Published: Aug. 29, 2016

Significance Cancer is a disease driven by rounds of genetic and epigenetic mutations that follow Darwinian evolution. The tumor for given patient often mixture multiple genotypically phenotypically distinct cell populations. This contributes to failures targeted therapies drug resistance, thus it important study intratumor heterogeneity. Here, we propose Canopy, statistical framework reconstruct phylogeny next-generation sequencing data from temporally and/or spatially separated resections the same patient. We show such analyses lead identification potentially useful prognostic/diagnostic biomarkers successfully recover tumor’s evolutionary history, validated single-cell sequencing. Canopy provides rigorous foundation analysis repeated evolving

Language: Английский

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Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(3), P. 517 - 525

Published: Jan. 10, 2019

Language: Английский

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Myelodysplastic syndrome progression to acute myeloid leukemia at the stem cell level

Nature Medicine, Journal Year: 2018, Volume and Issue: 25(1), P. 103 - 110

Published: Nov. 27, 2018

Language: Английский

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Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse

Blood, Journal Year: 2015, Volume and Issue: 126(22), P. 2491 - 2501

Published: Oct. 5, 2015

Language: Английский

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