Browsing by author "Graham, Trevor"

Now showing items 21-38 of 38

    • Measuring Clonal Evolution in Cancer with Genomics. 

      Williams, MJ; Sottoriva, A; Graham, TA (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 ...

    • Measuring single cell divisions in human tissues from multi-region sequencing data. 

      Werner, B; Case, J; Williams, MJ; Chkhaidze, K; Temko, D; et al. (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 ...

    • Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios. 

      Williams, MJ; Zapata, L; Werner, B; Barnes, CP; Sottoriva, A; et al. (ELIFE SCIENCES PUBLICATIONS LTD, 2020-03-30)
      The distribution of fitness effects (DFE) defines how new mutations spread through an evolving population. The ratio of non-synonymous to synonymous mutations (dN/dS) has become a popular method to detect selection in ...

    • The mutational signatures of formalin fixation on the human genome. 

      Guo, Q; Lakatos, E; Bakir, IA; Curtius, K; Graham, TA; et al. (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 ...

    • Pan-cancer analysis of the extent and consequences of intratumor heterogeneity. 

      Andor, N; Graham, TA; Jansen, M; Xia, LC; Aktipis, CA; et al. (NATURE PUBLISHING GROUP, 2016-01-01)
      Intratumor heterogeneity (ITH) drives neoplastic progression and therapeutic resistance. We used the bioinformatics tools 'expanding ploidy and allele frequency on nested subpopulations' (EXPANDS) and PyClone to detect ...

    • Phenotypic noise and plasticity in cancer evolution. 

      Whiting, FJH; Househam, J; Baker, A-M; Sottoriva, A; Graham, TA (Elsevier BV, 2023-11-13)
      Non-genetic alterations can produce changes in a cell's phenotype. In cancer, these phenomena can influence a cell's fitness by conferring access to heritable, beneficial phenotypes. Herein, we argue that current discussions ...

    • Phenotypic plasticity and genetic control in colorectal cancer evolution. 

      Househam, J; Heide, T; Cresswell, GD; Spiteri, I; Kimberley, C; et al. (NATURE PORTFOLIO, 2022-11-24)
      Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity1. The interplay of these biological processes and their respective contributions to tumour evolution remain ...

    • Quantification of subclonal selection in cancer from bulk sequencing data. 

      Williams, MJ; Werner, B; Heide, T; Curtis, C; Barnes, CP; et al. (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 ...

    • Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns. 

      Bollen, Y; Stelloo, E; van Leenen, P; van den Bos, M; Ponsioen, B; et al. (NATURE PORTFOLIO, 2021-08-01)
      Central to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at ...

    • Resolving genetic heterogeneity in cancer. 

      Turajlic, S; Sottoriva, A; Graham, T; Swanton, C (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 ...

    • Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution. 

      Baker, A-M; Huang, W; Wang, X-MM; Jansen, M; Ma, X-J; et al. (NATURE PUBLISHING GROUP, 2017-12-08)
      Intra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance and disease recurrence, and is a read-out of tumor growth. Current genetic ITH analysis methods do not preserve spatial context and may not ...

    • Spatially constrained tumour growth affects the patterns of clonal selection and neutral drift in cancer genomic data. 

      Chkhaidze, K; Heide, T; Werner, B; Williams, MJ; Huang, W; et al. (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. 

      Caravagna, G; Heide, T; Williams, MJ; Zapata, L; Nichol, D; et al. (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 ...

    • The co-evolution of the genome and epigenome in colorectal cancer 

      Sottoriva, A; Heide, T; Cresswell, G; Spiteri, I; Lynn, C; et al. (2021-07-12)
      Colorectal malignancies are a leading cause of cancer death. Despite large-scale genomic efforts, DNA mutations do not fully explain malignant evolution. Here we study the co-evolution of the genome and epigenome of ...

    • The co-evolution of the genome and epigenome in colorectal cancer. 

      Heide, T; Househam, J; Cresswell, GD; Spiteri, I; Lynn, C; et al. (NATURE PORTFOLIO, 2022-11-24)
      Colorectal malignancies are a leading cause of cancer-related death1 and have undergone extensive genomic study2,3. However, DNA mutations alone do not fully explain malignant transformation4-7. Here we investigate the ...

    • The evolutionary landscape of colorectal tumorigenesis. 

      Cross, W; Kovac, M; Mustonen, V; Temko, D; Davis, H; et al. (NATURE PORTFOLIO, 2018-10-01)
      The evolutionary events that cause colorectal adenomas (benign) to progress to carcinomas (malignant) remain largely undetermined. Using multi-region genome and exome sequencing of 24 benign and malignant colorectal tumours, ...

    • The MOBSTER R package for tumour subclonal deconvolution from bulk DNA whole-genome sequencing data. 

      Caravagna, G; Sanguinetti, G; Graham, TA; Sottoriva, A (BMC, 2020-11-17)
      BACKGROUND: The large-scale availability of whole-genome sequencing profiles from bulk DNA sequencing of cancer tissues is fueling the application of evolutionary theory to cancer. From a bulk biopsy, subclonal deconvolution ...

    • Virtual alignment of pathology image series for multi-gigapixel whole slide images. 

      Gatenbee, CD; Baker, A-M; Prabhakaran, S; Swinyard, O; Slebos, RJC; et al. (NATURE PORTFOLIO, 2023-07-26)
      Interest in spatial omics is on the rise, but generation of highly multiplexed images remains challenging, due to cost, expertise, methodical constraints, and access to technology. An alternative approach is to register ...