Advanced search
Start date
Betweenand
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

signeR: an empirical Bayesian approach to mutational signature discovery

Full text
Author(s):
Rosales, Rafael A. ; Drummond, Rodrigo D. ; Valieris, Renan ; Dias-Neto, Emmanuel ; da Silva, Israel T.
Total Authors: 5
Document type: Journal article
Source: Bioinformatics; v. 33, n. 1, p. 8-16, JAN 1 2017.
Web of Science Citations: 19
Abstract

Motivation: Mutational signatures can be used to understand cancer origins and provide a unique opportunity to group tumor types that share the same origins and result from similar processes. These signatures have been identified from high throughput sequencing data generated from cancer genomes by using non-negative matrix factorisation (NMF) techniques. Current methods based on optimization techniques are strongly sensitive to initial conditions due to high dimensionality and nonconvexity of the NMF paradigm. In this context, an important question consists in the determination of the actual number of signatures that best represent the data. The extraction of mutational signatures from high-throughput data still remains a daunting task. Results: Here we present a new method for the statistical estimation of mutational signatures based on an empirical Bayesian treatment of the NMF model. While requiring minimal intervention from the user, our method addresses the determination of the number of signatures directly as a model selection problem. In addition, we introduce two new concepts of significant clinical relevance for evaluating the mutational profile. The advantages brought by our approach are shown by the analysis of real and synthetic data. The later is used to compare our approach against two alternative methods mostly used in the literature and with the same NMF parametrization as the one considered here. Our approach is robust to initial conditions and more accurate than competing alternatives. It also estimates the correct number of signatures even when other methods fail. Results on real data agree well with current knowledge. (AU)

FAPESP's process: 14/26897-0 - Epidemiology and genomics of gastric adenocarcinomas in Brazil
Grantee:Emmanuel Dias-Neto
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 15/19324-6 - Retrotransposons and nucleic acid-editing enzymes: activation, somatic events and association with cancer
Grantee:Israel Tojal da Silva
Support Opportunities: Regular Research Grants