RESUMEN
SUMMARY: A main task in computational cancer analysis is the identification of patient subgroups (i.e. cohorts) based on metadata attributes (patient stratification) or genomic markers of response (biomarkers). Coral is a web-based cohort analysis tool that is designed to support this task: Users can interactively create and refine cohorts, which can then be compared, characterized and inspected down to the level of single items. Coral visualizes the evolution of cohorts and also provides intuitive access to prevalence information. Furthermore, findings can be stored, shared and reproduced via the integrated session management. Coral is pre-loaded with data from over 128 000 samples from the AACR Project GENIE, the Cancer Genome Atlas and the Cell Line Encyclopedia. AVAILABILITY AND IMPLEMENTATION: Coral is publicly available at https://coral.caleydoapp.org. The source code is released at https://github.com/Caleydo/coral. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Antozoos , Neoplasias , Animales , Genoma , Programas Informáticos , InternetRESUMEN
The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.
Asunto(s)
Neoplasias Faciales/veterinaria , Inestabilidad Genómica , Marsupiales/genética , Mutación , Animales , Evolución Clonal , Especies en Peligro de Extinción , Neoplasias Faciales/epidemiología , Neoplasias Faciales/genética , Neoplasias Faciales/patología , Femenino , Estudio de Asociación del Genoma Completo , Masculino , Datos de Secuencia Molecular , Tasmania/epidemiologíaRESUMEN
All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.