The Hierarchical Modular Structure of HER2+Breast Cancer Network
Por:
Antonio Alcala-Corona, Sergio, Espinal-Enriquez, Jesus, de Anda-Jauregui, Guillermo, Hernandez-Lemus, Enrique
Publicada:
11 oct 2018
Resumen:
HER2-enriched breast cancer is a complex disease characterized by the
overexpression of the ERBB2 amplicon. While the effects of this genomic
aberration on the pathology have been studied, genome-wide deregulation
patterns in this subtype of cancer are also observed. A novel approach
to the study of this malignant neoplasy is the use of transcriptional
networks. These networks generally exhibit modular structures, which in
turn may be associated to biological processes. This modular regulation
of biological functions may also exhibit a hierarchical structure, with
deeper levels of modular organization accounting for more specific
functional regulation. In this work, we identified the most probable
(maximum likelihood) model of the hierarchical modular structure of the
HER2-enriched transcriptional network as reconstructed from gene
expression data, and analyzed the statistical associations of modules
and submodules to biological functions. We found modular structures,
independent from direct ERBB2 amplicon regulation, involved in different
biological functions such as signaling, immunity, and cellular
morphology. Higher resolution submodules were identified in more
specific functions, such asmicro-RNA regulation and the activation of
viral-like immune response. We propose the approach presented here as
one that may help to unveil mechanisms involved in the development of
the pathology.
Filiaciones:
Antonio Alcala-Corona, Sergio:
Natl Inst Genom Med, Computat Genom, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Ctr Ciencias Complejidad, Ciudad De Mexico, Mexico
Espinal-Enriquez, Jesus:
Natl Inst Genom Med, Computat Genom, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Ctr Ciencias Complejidad, Ciudad De Mexico, Mexico
de Anda-Jauregui, Guillermo:
Natl Inst Genom Med, Computat Genom, Mexico City, DF, Mexico
Hernandez-Lemus, Enrique:
Natl Inst Genom Med, Computat Genom, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Ctr Ciencias Complejidad, Ciudad De Mexico, Mexico
|