|
A
network of disorders and disease genes linked by known disorder–gene
associations offers a platform to explore in a single graph-theoretic
framework all known phenotype and disease gene associations, indicating the
common genetic origin of many diseases. Genes associated with similar
disorders show both higher likelihood of physical interactions between their
products and higher expression profiling similarity for their transcripts,
supporting the existence of distinct disease-specific functional modules. We
find that essential human genes are likely to encode hub proteins and are
expressed widely in most tissues. This suggests that disease genes also would
play a central role in the human interactome. In contrast, we find that the
vast majority of disease genes are nonessential and show no tendency to
encode hub proteins, and their expression pattern indicates that they are
localized in the functional periphery of the network. A selection-based model
explains the observed difference between essential and disease genes and also
suggests that diseases caused by somatic mutations should not be peripheral,
a prediction we confirm for cancer genes.
|
