Network biology is a rapidly developing area of biomedical research and reflects the current view that complex phenotypes, such as disease susceptibility, are not the result of single gene mutations that act in isolation but are rather due to the perturbation of a gene’s network context. Understanding the topology of these molecular interaction networks and identifying the molecules that play central roles in their structure and regulation is a key to understanding complex systems. The falling cost of next-generation sequencing is now enabling researchers to routinely catalogue the molecular components of these networks at a genome-wide scale and over a large number of different conditions. In this review, we describe how to use publicly available bioinformatics tools to integrate genome-wide ‘omics’ data into a network of experimentally-supported molecular interactions. In addition, we describe how to visualize and analyze these networks to identify topological features of likely functional relevance, including network hubs, bottlenecks and modules. We show that network biology provides a powerful conceptual approach to integrate and find patterns in genome-wide genomic data but we also discuss the limitations and caveats of these methods, of which researchers adopting these methods must remain aware.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-016-0205-1) contains supplementary material, which is available to authorized users.

PurposeSuccess of Ebola virus (EBOV) as a human pathogen relates at the molecular level primarily to blockade the host cell type I interferon (IFN) antiviral response. Most individuals who survive Ebola virus disease (EVD) develop a chronic disease syndrome: approximately one-quarter of survivors suffer from uveitis, which has been associated with presence of EBOV within the eye. Clinical observations of post-Ebola uveitis indicate involvement of retinal pigment epithelial cells.MethodsWe inoculated ARPE-19 human retinal pigment epithelial cells with EBOV, and followed course of infection by immunocytochemistry and measurement of titer in culture supernatant. To interrogate transcriptional responses of infected cells, we combined RNA sequencing with in silico pathway, gene ontology, transcription factor binding site, and network analyses. We measured infection-induced changes of selected transcripts by reverse transcription-quantitative polymerase chain reaction.ResultsHuman retinal pigment epithelial cells were permissive to infection with EBOV, and supported viral replication and release of virus in high titer. Unexpectedly, 28% of 560 upregulated transcripts in EBOV-infected cells were type I IFN responsive, indicating a robust type I IFN response. Following EBOV infection, cells continued to express multiple immunomodulatory molecules linked to ocular immune privilege.ConclusionsHuman retinal pigment epithelial cells may serve as an intraocular reservoir for EBOV, and the molecular response of infected cells may contribute to the persistence of live EBOV within the human eye.Translational RelevanceThis bedside-to-bench research links ophthalmic findings in survivors of EVD who suffer from uveitis with interactions between retinal pigment epithelial cells and EBOV.