RESOLVE - RESOLVE: An R package for the efficient analysis of mutational
signatures from cancer genomes
Cancer is a genetic disease caused by somatic mutations in
genes controlling key biological functions such as cellular
growth and division. Such mutations may arise both through
cell-intrinsic and exogenous processes, generating
characteristic mutational patterns over the genome named
mutational signatures. The study of mutational signatures have
become a standard component of modern genomics studies, since
it can reveal which (environmental and endogenous) mutagenic
processes are active in a tumor, and may highlight markers for
therapeutic response. Mutational signatures computational
analysis presents many pitfalls. First, the task of determining
the number of signatures is very complex and depends on
heuristics. Second, several signatures have no clear etiology,
casting doubt on them being computational artifacts rather than
due to mutagenic processes. Last, approaches for signatures
assignment are greatly influenced by the set of signatures used
for the analysis. To overcome these limitations, we developed
RESOLVE (Robust EStimation Of mutationaL signatures Via
rEgularization), a framework that allows the efficient
extraction and assignment of mutational signatures. RESOLVE
implements a novel algorithm that enables (i) the efficient
extraction, (ii) exposure estimation, and (iii) confidence
assessment during the computational inference of mutational
signatures.