Jan 13, 2016

Mutation signatures reveal biological processes in human cancer

BioRxiv : the Preprint Server for Biology
Kyle CovingtonDavid A Wheeler


Replication errors in the genome accumulate from a variety of mutational processes, which leave a history of mutations on the affected genome. The relative contribution of each mutational process has been characterized by non-negative matrix factorization and has lead to deeper insight into both mutational and repair processes contributing to cancer. However current implementations of NMF have left unresolved some specific patterns that should be present in the mutation data and have not generated signatures designed for classification. Here, we use a variant of NMF, termed non-smooth NMF, to generate sparse matrix factorizations of somatic mutation profiles present in 7129 tumors. nsNMF factorization revealed 21 mutational signatures. We found three APOBEC mutational processes clearly segregating with the published APOBEC enzymology and trans-lesion repair processes. We discovered several signatures differed between geographic locations even between closely related tissues.

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Mentioned in this Paper

Non-negative Matrix Factorization
Somatic Mutation
Enzymatic Biochemistry
Extracellular Matrix
Virus Replication
Malignant Neoplasms

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