Ensemble inference by integrative cancer networks

Epigenetics implies heritable changes in gene expression without involvement of DNA sequence. Gene silencing is a com- plex biological process which involves methylation, and leads to disease devel- opment once dysregulated. The high fre- quency of epigenetic changes in cancer has motivated research into new therapeutic approaches aimed to reverse gene silenc- ing. DNA methylation inhibitors, together with histone deacetylase inhibitors, are examples of valid drug targets con- ceived toward the re-activation of silenced genes. Future avenues include activa- tion of single genes by exploiting sin- gle agents or also the combination of epigenetic drugs, thus emphasizing the synergistic activities between DNA methy- lation and HDAC inhibitors, and con- sidering likely non-specificity in terms of gene re-activation. The identification of modules at the network scale leads to an integrative systems approach which goes beyond single marker analysis and exploits synergistic marker dynamics in support of combinatorial experiments. Our pre- liminary results show that the recovery of latent connectivity may re-position the markers depending on the module- integrated biodata multitude and on the nature of the edges linking the nodes.