Browsing Other ICR Research by author "Graham, Trevor"

Now showing items 1-13 of 13

    • A Big Bang model of human colorectal tumor growth. 

      Sottoriva, A; Kang, H; Ma, Z; Graham, TA; Salomon, MP; et al. (NATURE PUBLISHING GROUP, 2015-03-01)
      What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion ...

    • Between-region genetic divergence reflects the mode and tempo of tumor evolution. 

      Sun, R; Hu, Z; Sottoriva, A; Graham, TA; Harpak, A; et al. (NATURE PUBLISHING GROUP, 2017-06-05)
      Given the implications of tumor dynamics for precision medicine, there is a need to systematically characterize the mode of evolution across diverse solid tumor types. In particular, methods to infer the role of natural ...

    • Catch my drift? Making sense of genomic intra-tumour heterogeneity. 

      Sottoriva, A; Barnes, CP; Graham, TA (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 ...

    • Evolutionary dynamics of neoantigens in growing tumors. 

      Lakatos, E; Williams, MJ; Schenck, RO; Cross, WCH; Househam, J; et al. (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 ...

    • Identification of neutral tumor evolution across cancer types. 

      Williams, MJ; Werner, B; Barnes, CP; Graham, TA; Sottoriva, A (NATURE PUBLISHING GROUP, 2016-03-01)
      Despite extraordinary efforts to profile cancer genomes, interpreting the vast amount of genomic data in the light of cancer evolution remains challenging. Here we demonstrate that neutral tumor evolution results in a ...

    • Measuring cancer evolution from the genome. 

      Graham, TA; Sottoriva, A (WILEY-BLACKWELL, 2017-01-01)
      The temporal dynamics of cancer evolution remain elusive, because it is impractical to longitudinally observe cancers unperturbed by treatment. Consequently, our knowledge of how cancers grow largely derives from inferences ...

    • 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 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 ...

    • 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 ...

    • 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 ...

    • 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 ...