In @entity66 , various combinations of genomic perturbations often lead to the same phenotype. On a molecular level, combinations of genomic perturbations are assumed to dys-regulate the same cellular pathways. Such a pathway-centric perspective is fundamental to understanding the mechanisms of @entity66 and the identification of potential drug targets. In order to provide an integrated perspective on complex disease mechanisms, we developed a novel computational method to simultaneously identify causal genes and dys-regulated pathways. First, we identified a representative set of genes that are differentially expressed in @entity5 compared to non-tumor control cases. Assuming that disease-associated gene expression changes are caused by genomic alterations, we determined potential paths from such genomic causes to target genes through a network of molecular interactions. Applying our method to sets of genomic alterations and gene expression profiles of 158 @entity463 ( @entity463 ) @entity1 we uncovered candidate causal genes and causal paths that are potentially responsible for the altered expression of disease genes. We discovered a set of putative causal genes that potentially play a role in the disease. Combining an expression Quantitative Trait Loci (eQTL) analysis with pathway information, our approach allowed us not only to identify potential causal genes but also to find intermediate nodes and pathways mediating the information flow between causal and target genes. Our results indicate that different genomic perturbations indeed dys-regulate the same functional pathways, supporting a pathway-centric perspective of @entity5 . While copy number alterations and gene expression data of @entity463 @entity1 provided opportunities to test our approach, our method can be applied to any disease system where genetic variations play a fundamental causal role.

Identifying causal genes and dysregulated pathways in XXXX .

@entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity1 :: ('9606', 'Species') :: ['patients'] @entity463 :: ('MESH:D005909', 'Disease') :: ['GBM', 'glioblastoma', 'Glioblastoma multiforme'] @entity66 :: ('MESH:D004194', 'Disease') :: ['complex diseases']
@entity66 :: (MESH:D004194,Disease) :: ['complex diseases']
