Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an interaction network obtained for genes of interest. Five major steps are described: (i) obtaining a gene or protein network, (ii) displaying the network using layout algorithms, (iii) integrating with gene expression and other functional attributes, (iv) identifying putative complexes and functional modules and (v) identifying enriched Gene Ontology annotations in the network. These steps provide a broad sample of the types of analyses performed by Cytoscape.

Large-scale gene expression studies provide significant insight into genes differentially regulated in disease processes such as cancer. However, these investigations offer limited understanding of multisystem, multicellular diseases such as atherosclerosis. A systems biology approach that accounts for gene interactions, incorporates nontranscriptionally regulated genes, and integrates prior knowledge offers many advantages. We performed a comprehensive gene level assessment of coronary atherosclerosis using 51 coronary artery segments isolated from the explanted hearts of 22 cardiac transplant patients. After histological grading of vascular segments according to American Heart Association guidelines, isolated RNA was hybridized onto a customized 22-K oligonucleotide microarray, and significance analysis of microarrays and gene ontology analyses were performed to identify significant gene expression profiles. Our studies revealed that loss of differentiated smooth muscle cell gene expression is the primary expression signature of disease progression in atherosclerosis. Furthermore, we provide insight into the severe form of coronary artery disease associated with diabetes, reporting an overabundance of immune and inflammatory signals in diabetics. We present a novel approach to pathway development based on connectivity, determined by language parsing of the published literature, and ranking, determined by the significance of differentially regulated genes in the network. In doing this, we identify highly connected "nexus" genes that are attractive candidates for therapeutic targeting and followup studies. Our use of pathway techniques to study atherosclerosis as an integrated network of gene interactions expands on traditional microarray analysis methods and emphasizes the significant advantages of a systems-based approach to analyzing complex disease.

Workstations and personal computers are increasingly being delivered with the ability to handle multimedia data; more and more of us are linked by high-speed digital networks. With multimedia communication environments becoming more commonplace, what have we learned from earlier experiences with prototype media environments? This paper reports on some of our experiences as developers, researchers and users of flexible, networked, multimedia computer environments, or "media spaces". It focusses on the lessons we can learn from extended, long-term use of media spaces, with connections that last not hours or days, but months or years. We take as our starting point a set of assumptions which differ from traditional analytical perspectives. In particular, we begin from the position that that real-world baseline is not always an appropriate point of comparison for new media technologies; that a set of complex and intricate communicative behaviours arise over time; and that media spaces connect not only individuals, but the wider social groups of which they form part. We outline a framework based on four perspectives -individual, interactional, communal and societal -from which to view the behaviour of individuals and groups linked by multimedia environments. On the basis of our long-term findings, we argue for a view of media spaces which, first, focuses on a wider interpretation of media space interaction than the traditional view of person-to-person connections, and, second, emphasises emergent communicative practices, rather than looking for the transfer of face-to-face behaviours.

Collaboration has long been of considerable interest in the CHI community. This paper proposes and explores the concept of network communities as a crucial part of this discussion. Network communities are a form of technologymediated environment that foster a sense of community among users. We consider several familiar systems and describe the shared characteristics these systems have developed to deal with critical concerns of collaboration. Based on our own experience as designers and users of a variety of network communities. we extend this initial design space along three dimensions: the articulation of a persistent sense of location, the boundary tensions between real and virtual worlds, and the emergence and evolution of community.

No abstract