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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 ...
Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell-like phenotype.
(AMER ASSOC ADVANCEMENT SCIENCE, 2020-08-05)
Blockade of epidermal growth factor receptor (EGFR) causes tumor regression in some patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs typically remain even after maximal response to ...
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 ...
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 ...
Cell Competition in Carcinogenesis.
(AMER ASSOC CANCER RESEARCH, 2022-12-16)
The majority of human cancers evolve over time through the stepwise accumulation of somatic mutations followed by clonal selection akin to Darwinian evolution. However, the in-depth mechanisms that govern clonal dynamics ...
The mutational signatures of formalin fixation on the human genome.
(NATURE PORTFOLIO, 2022-09-06)
Clinical archives of patient material near-exclusively consist of formalin-fixed and paraffin-embedded (FFPE) blocks. The ability to precisely characterise mutational signatures from FFPE-derived DNA has tremendous ...
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 ...
Detecting repeated cancer evolution from multi-region tumor sequencing data.
(NATURE PUBLISHING GROUP, 2018-08-31)
Recurrent successions of genomic changes, both within and between patients, reflect repeated evolutionary processes that are valuable for the anticipation of cancer progression. Multi-region sequencing allows the temporal ...
Classifying the evolutionary and ecological features of neoplasms.
(NATURE PUBLISHING GROUP, 2017-10-01)
Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive ...