Application of systems biology for understanding of disease and selection of molecular targets for therapy

The Herpesviridae are a large family of DNA viruses. Several members of this family are known to cause disease in animals and human. In particular there are several lines of evidence for involvement in human cancer and autoimmune conditions. Although this group of viruses has been investigated intensively for several decades molecular mechanisms and roles in the development of associated diseases are not yet fully understood. Bioinformatics and Systems Biology allow to incorporate current knowledge with high throughput Omics data to analyze them in the context of molecular networks. Among the applications of this development, effects of pathogen proteins and non-coding RNAs can be more readily understood by viewing their human targets in their functional-dependency network. Combination of generated networks with disease specific transcriptomics data allows to analyze the effect of pathogen proteins in the context of medically relevant phenomena. Additional enrichment with drug-target information allows generating new hypotheses for drug re-use or drug repositioning of currently available drugs to treat herpes virus associated diseases. Here we show publicly available Epstein-Barr virus data in the context of a meta-network which combines a proprietary human interaction network (omicsNET), drug-target networks, host-pathogen networks and orthology networks. EBV, a clinically relevant human Lymphocryptovirus, is of high immunological interest also due to its potential to bias natural immune responses by establishing (life-long) latent infection in memory B-cells. We thereby exemplify implications of a Systems view for better understanding of pathogen mode of action. Our work towards a methodological basis for selection of drugs which could be of interest in the treatment of this class of pathogens is presented. While investigating options for development of novel therapies we place particular focus on the application potentials of Systems Biology for selection of candidate vaccine targets in light of chronic infections not amenable to classical vaccination strategies.