WeSME: uncovering mutual exclusivity of cancer drivers and beyond.
Bioinformatics
; 33(6): 814-821, 2017 03 15.
Article
en En
| MEDLINE
| ID: mdl-27153670
ABSTRACT
Motivation Mutual exclusivity is a widely recognized property of many cancer drivers. Knowledge about these relationships can provide important insights into cancer drivers, cancer-driving pathways and cancer subtypes. It can also be used to predict new functional interactions between cancer driving genes and uncover novel cancer drivers. Currently, most of mutual exclusivity analyses are preformed focusing on a limited set of genes in part due to the computational cost required to rigorously compute P -values. Results:
To reduce the computing cost and perform less restricted mutual exclusivity analysis, we developed an efficient method to estimate P -values while controlling the mutation rates of individual patients and genes similar to the permutation test. A comprehensive mutual exclusivity analysis allowed us to uncover mutually exclusive pairs, some of which may have relatively low mutation rates. These pairs often included likely cancer drivers that have been missed in previous analyses. More importantly, our results demonstrated that mutual exclusivity can also provide information that goes beyond the interactions between cancer drivers and can, for example, elucidate different mutagenic processes in different cancer groups. In particular, including frequently mutated, long genes such as TTN in our analysis allowed us to observe interesting patterns of APOBEC activity in breast cancer and identify a set of related driver genes that are highly predictive of patient survival. In addition, we utilized our mutual exclusivity analysis in support of a previously proposed model where APOBEC activity is the underlying process that causes TP53 mutations in a subset of breast cancer cases. Availability and Implementation http//www.ncbi.nlm.nih.gov/CBBresearch/Przytycka/index.cgi#wesme. Contact przytyck@ncbi.nlm.nih.gov. Supplementary information Supplementary data are available at Bioinformatics online.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Biología Computacional
/
Mutación
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Bioinformatics
Asunto de la revista:
INFORMATICA MEDICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos