Discovering causal pathways linking genomic events to transcriptional states using Tied Diffusion Through Interacting Events (TieDIE).
Bioinformatics
; 29(21): 2757-64, 2013 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-23986566
ABSTRACT
MOTIVATION Identifying the cellular wiring that connects genomic perturbations to transcriptional changes in cancer is essential to gain a mechanistic understanding of disease initiation, progression and ultimately to predict drug response. We have developed a method called Tied Diffusion Through Interacting Events (TieDIE) that uses a network diffusion approach to connect genomic perturbations to gene expression changes characteristic of cancer subtypes. The method computes a subnetwork of protein-protein interactions, predicted transcription factor-to-target connections and curated interactions from literature that connects genomic and transcriptomic perturbations. RESULTS:
Application of TieDIE to The Cancer Genome Atlas and a breast cancer cell line dataset identified key signaling pathways, with examples impinging on MYC activity. Interlinking genes are predicted to correspond to essential components of cancer signaling and may provide a mechanistic explanation of tumor character and suggest subtype-specific drug targets.AVAILABILITY:
Software is available from the Stuart lab's wiki https//sysbiowiki.soe.ucsc.edu/tiedie. CONTACT jstuart@ucsc.edu. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
/
Redes Reguladoras de Genes
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article