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Resolving genetic heterogeneity in cancer.
(NATURE PUBLISHING GROUP, 2019-07-01)
To a large extent, cancer conforms to evolutionary rules defined by the rates at which clones mutate, adapt and grow. Next-generation sequencing has provided a snapshot of the genetic landscape of most cancer types, and ...
Measuring single cell divisions in human tissues from multi-region sequencing data.
(NATURE PUBLISHING GROUP, 2020-02-25)
Both normal tissue development and cancer growth are driven by a branching process of cell division and mutation accumulation that leads to intra-tissue genetic heterogeneity. However, quantifying somatic evolution in ...
Quantification of subclonal selection in cancer from bulk sequencing data.
(NATURE PUBLISHING GROUP, 2018-05-28)
Subclonal architectures are prevalent across cancer types. However, the temporal evolutionary dynamics that produce tumor subclones remain unknown. Here we measure clone dynamics in human cancers by using computational ...
Spatially constrained tumour growth affects the patterns of clonal selection and neutral drift in cancer genomic data.
(PUBLIC LIBRARY SCIENCE, 2019-07-29)
Quantification of the effect of spatial tumour sampling on the patterns of mutations detected in next-generation sequencing data is largely lacking. Here we use a spatial stochastic cellular automaton model of tumour growth ...
Measuring Clonal Evolution in Cancer with Genomics.
(ANNUAL REVIEWS, 2019-08-31)
Cancers originate from somatic cells in the human body that have accumulated genetic alterations. These mutations modify the phenotype of the cells, allowing them to escape the homeostatic regulation that maintains normal ...
Subclonal reconstruction of tumors by using machine learning and population genetics.
(NATURE PUBLISHING GROUP, 2020-09-01)
Most cancer genomic data are generated from bulk samples composed of mixtures of cancer subpopulations, as well as normal cells. Subclonal reconstruction methods based on machine learning aim to separate those subpopulations ...
Evolutionary dynamics of neoantigens in growing tumors.
(NATURE PORTFOLIO, 2020-10-01)
Cancers accumulate mutations that lead to neoantigens, novel peptides that elicit an immune response, and consequently undergo evolutionary selection. Here we establish how negative selection shapes the clonality of ...
Clinical trial designs for evaluating and exploiting cancer evolution.
(ELSEVIER SCI LTD, 2023-07-01)
The evolution of drug-resistant cell subpopulations causes cancer treatment failure. Current preclinical evidence shows that it is possible to model herding of clonal evolution and collateral sensitivity where an initial ...
Immune selection determines tumor antigenicity and influences response to checkpoint inhibitors.
(NATURE PORTFOLIO, 2023-03-01)
In cancer, evolutionary forces select for clones that evade the immune system. Here we analyzed >10,000 primary tumors and 356 immune-checkpoint-treated metastases using immune dN/dS, the ratio of nonsynonymous to synonymous ...
Catch my drift? Making sense of genomic intra-tumour heterogeneity.
(ELSEVIER, 2017-04-01)
The cancer genome is shaped by three components of the evolutionary process: mutation, selection and drift. While many studies have focused on the first two components, the role of drift in cancer evolution has received ...