ArticlePLoS computational biology2014
Inferring clonal composition from multiple sections of a breast cancer.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
- A clinical solution for tracking clonal evolution of acute myeloid leukemia after allogeneic transplantation using bulk next generation sequencing.Bone marrow transplantation · 2025Article
- Joint inference of cell lineage and mitochondrial evolution from single-cell sequencing data.Bioinformatics (Oxford, England) · 2024Article
- Computational Methods Summarizing Mutational Patterns in Cancer: Promise and Limitations for Clinical Applications.Cancers · 2023Review
- Extrinsic cell death pathway plasticity: a driver of clonal evolution in cancer?Cell death discovery · 2022Review
- Mechanisms of breast cancer metastasis.Clinical & experimental metastasis · 2022Review
- Article
- DEVOLUTION-A method for phylogenetic reconstruction of aneuploid cancers based on multiregional genotyping data.Communications biology · 2021Article
- Conifer: clonal tree inference for tumor heterogeneity with single-cell and bulk sequencing data.BMC bioinformatics · 2021Article
- A statistical approach for tracking clonal dynamics in cancer using longitudinal next-generation sequencing data.Bioinformatics (Oxford, England) · 2021Article
- Multiregion Sequence Analysis to Predict Intratumor Heterogeneity and Clonal Evolution.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Reconstructing tumor evolutionary histories and clone trees in polynomial-time with SubMARine.PLoS computational biology · 2021Article
- Quantifying the influence of mutation detection on tumour subclonal reconstruction.Nature communications · 2020Article
- Power and pitfalls of computational methods for inferring clone phylogenies and mutation orders from bulk sequencing data.Scientific reports · 2020Article
- Meltos: multi-sample tumor phylogeny reconstruction for structural variants.Bioinformatics (Oxford, England) · 2020Article
- DENDRO: genetic heterogeneity profiling and subclone detection by single-cell RNA sequencing.Genome biology · 2020Article
- Neural Network Deconvolution Method for Resolving Pathway-Level Progression of Tumor Clonal Expression Programs With Application to Breast Cancer Brain Metastases.Frontiers in physiology · 2020Article
- Algorithmic approaches to clonal reconstruction in heterogeneous cell populations.Quantitative biology (Beijing, China) · 2019Article
- CALDER: Inferring Phylogenetic Trees from Longitudinal Tumor Samples.Cell systems · 2019Article
- Integrative inference of subclonal tumour evolution from single-cell and bulk sequencing data.Nature communications · 2019Article
- BAMSE: Bayesian model selection for tumor phylogeny inference among multiple samples.BMC bioinformatics · 2019Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Cancers arise from successive rounds of mutation and selection, generating clonal populations that vary in size, mutational content and drug responsiveness. Ascertaining the clonal composition of a tumor is therefore important both for prognosis and therapy. 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 a major challenge. 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 using this model. We demonstrate, via simulation, the validity of the approach, and then use our algorithm to assess the clonal composition of a primary breast cancer and associated metastatic lymph node. After dividing the tumor into subsections, we perform exome sequencing for each subsection to assess mutational content, followed by deep sequencing to precisely count normal and variant alleles within each subsection. By quantifying the frequencies of 17 somatic variants, we demonstrate that our algorithm predicts clonal relationships that are both phylogenetically and spatially plausible. Applying this method to larger numbers of tumors should cast light on the clonal evolution of cancers in space and time.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.