Figure 1

Conceptual models for disrupted pathways. This figure describes two conceptual models for inferring activity of disrupted pathways. (A) Three out of six member genes in the pathway are significantly altered by copy number changes. In this case, overrepresentation-based gene set enrichment analysis and pathway-based analysis could identify the pathway as an enriched pathway with altered genes, since many member genes in the pathway are altered in copy number changes. (B) No member gene in the pathway is altered by copy number changes, but member genes in the pathway are interacting with many other altered genes in the protein-protein interaction network. Existing gene set enrichment analysis and pathway-based analysis would fail to identify the pathway as a disrupted pathway, due to the lack of overlapping altered genes with member genes in the pathway. However, by applying a machine learning method, which propagates the activity score of genes to other genes by exploring cluster structures in the protein-protein interaction network, our approach could identify the pathway as a disrupted pathway, since many member genes in the pathway are interacting with other altered genes (i.e. significantly altered genes in copy number alterations could alter the activity (or function) of member genes through interactions).