  Disease-causing mutations usually change the interacting partners of mutant
proteins. In this article, we propose that the biological consequences of
mutation are directly related to the alteration of corresponding protein
protein interaction networks (PPIN). Mutation of Huntingtin (HTT) which causes
Huntington's disease (HD) and mutations to TP53 which is associated with
different cancers are studied as two example cases. We construct the PPIN of
wild type and mutant proteins separately and identify the structural modules of
each of the networks. The functional role of these modules are then assessed by
Gene Ontology (GO) enrichment analysis for biological processes (BPs). We find
that a large number of significantly enriched (p<0.0001) GO terms in mutant
PPIN were absent in the wild type PPIN indicating the gain of BPs due to
mutation. Similarly some of the GO terms enriched in wild type PPIN cease to
exist in the modules of mutant PPIN, representing the loss. GO terms common in
modules of mutant and wild type networks indicate both loss and gain of BPs. We
further assign relevant biological function(s) to each module by classifying
the enriched GO terms associated with it. It turns out that most of these
biological functions in HTT networks are already known to be altered in HD and
those of TP53 networks are altered in cancers. We argue that gain of BPs, and
the corresponding biological functions, are due to new interacting partners
acquired by mutant proteins. The methodology we adopt here could be applied to
genetic diseases where mutations alter the ability of the protein to interact
with other proteins.

Molecular Networks;Biological Physics