Discerning mechanistically rewired biological pathways by cumulative interaction heterogeneity statistics.
Sci Rep
; 5: 9634, 2015 Apr 28.
Article
em En
| MEDLINE
| ID: mdl-25921728
Changes in response of a biological pathway could be a consequence of either pathway rewiring, changed input, or a combination of both. Most pathway analysis methods are not designed for mechanistic rewiring such as regulatory element variations. This limits our understanding of biological pathway evolution. Here we present a Q-method to discern whether changed pathway response is caused by mechanistic rewiring of pathways due to evolution. The main innovation is a cumulative pathway interaction heterogeneity statistic accounting for rewiring-specific effects on the rate of change of each molecular variable across conditions. The Q-method remarkably outperformed differential-correlation based approaches on data from diverse biological processes. Strikingly, it also worked well in differentiating rewired chaotic systems, whose dynamics are notoriously difficult to predict. Applying the Q-method on transcriptome data of four yeasts, we show that pathway interaction heterogeneity for known metabolic and signaling pathways is indeed a predictor of interspecies genetic rewiring due to unbalanced TATA box-containing genes among the yeasts. The demonstrated effectiveness of the Q-method paves the way to understanding network evolution at the resolution of functional biological pathways.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leveduras
/
Transdução de Sinais
/
Redes e Vias Metabólicas
/
Redes Reguladoras de Genes
/
Transcriptoma
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Reino Unido