Somatic mutations arise in the DNA of all the cells of the human body and occur throughout life. They are the consequence of mutational processes that may be exogenous in origin or due to endogenous cellular activities, and are a key component in understanding cancer development and progression. Different mutational processes generate observable patterns of mutation within the genome. These patterns are called mutational signatures.
Signal is the product of the Physiology of Mutagenesis research team at University of Cambridge, as part of the COMSIG Consortium. With teams in Cambridge and London, COMSIG is dedicated to exploring the biological underpinnings of mutational signatures and their potential clinical applications.
Signal is the most up-to-date repository of knowledge and expertise in the field of mutational signatures, and provides a comprehensive workflow for your own mutational signature analysis.
Explore the substitution, insertion/deletion and rearrangement mutational signatures found in more than 3,000 whole-genome-sequenced cancer samples and in hundreds of isogenic cell-based experiments involving exposures to environmental mutagens and DNA repair/replication gene knockouts.
We extracted substitution and rearrangement signatures from 3,107 cancer samples generated by the International Cancer Genome Consortium.
Signatures were extracted independently for each organ of origin and then clustered to form a set of reference signatures. This updated framework for signature extraction highlights signature variability across organs, and leverages the organ-specificity of signatures for improved fitting.
Human IPS cells were exposed to 79 separate environmental mutagens, yielding 54 substitution and 11 indel signatures.
Human cancers are noisy experimental systems where the final mutational profiles are made up of many signatures arising from different processes. This experiment sought to examine the signatures associated with a selection of environmental mutagens under highly-controlled conditions.
9 genes relating to DNA repair were knocked out using CRISPR-Cas9 technology in Human HAP-1 cells.
Human cancers are noisy experimental systems where the final mutational profiles are made up of many signatures arising from different processes. This experiment sought to examine the signatures associated with knockouts of a selection of genes related to DNA repair/replication under highly-controlled conditions.