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.

A multiple view system uses two or more distinct views to support the investigation of a single conceptual entity. Many such systems exist, ranging from computer-aided design (CAD) systems for chip design that display both the logical structure and the actual geometry of the integrated circuit to overview-plus-detail systems that show both an overview for context and a zoomed-in-view for detail. Designers of these systems must make a variety of design decisions, ranging from determining layout to constructing sophisticated coordination mechanisms. Surprisingly, little work has been done to characterize these systems or to express guidelines for their design. Based on a workshop discussion of multiple views, and based on our own design and implementation experience with these systems, we present eight guidelines for the design of multiple view systems.

Summary: GLay provides Cytoscape users an assorted collection of versatile community structure algorithms and graph layout functions for network clustering and structured visualization. High performance is achieved by dynamically linking highly optimized C functions to the Cytoscape JAVA program, which makes GLay especially suitable for decomposition, display and exploratory analysis of large biological networks.Availability: http://brainarray.mbni.med.umich.edu/glay/Contact: sugang@umich.edu

Quality of Service, user perception, eCommerce, server design, internet, web server design As the number of Web users and the diversity of Web applications continues to explode, Web Quality of Service (QoS) is an increasingly critical issue in the domain of e-Commerce. This paper presents experiments designed to estimate users' tolerance of QoS in the context of e-commerce. In addition to objective measures we discuss contextual factors that influence these thresholds and show how users' conceptual models of Web tasks affect their expectations. We then show how user thresholds of tolerance can be taken into account when designing web servers. This integration of user requirements for QoS into systems design is ultimately of benefit to all stakeholders in the design of Internet services. AbstractAs the number of Web users and the diversity of Web applications continues to explode, Web Quality of Service (QoS) is an increasingly critical issue in the domain of e-Commerce [re]. This paper presents experiments designed to estimate users' tolerance of QoS in the context of e-commerce. In addition to objective measures we discuss contextual factors that influence these thresholds and show how users' conceptual models of Web tasks affect their expectations. We then show how user thresholds of tolerance can be taken into account when designing web servers. This integration of user requirements for QoS into systems design is ultimately of benefit to all stakeholders in the design of Internet services.

No abstract

Eleven PC-owning families were interviewed at home about their use of conventional and digital photos. They also completed photo diaries and recorded photo-sharing conversations that occurred spontaneously over a three month period after the in-home interviews. From an analysis of the resulting materials we illustrate the strengths and weaknesses of past and present technology for photo sharing. These allow us to prioritise user requirements for a range of future photo-sharing technologies or 'photoware'.

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.

The role of alternative splicing in self-renewal, pluripotency and tissue lineage specification of human embryonic stem cells (hESCs) is largely unknown. To better define these regulatory cues, we modified the H9 hESC line to allow selection of pluripotent hESCs by neomycin resistance and cardiac progenitors by puromycin resistance. Exon-level microarray expression data from undifferentiated hESCs and cardiac and neural precursors were used to identify splice isoforms with cardiac-restricted or common cardiac/neural differentiation expression patterns. Splice events for these groups corresponded to the pathways of cytoskeletal remodeling, RNA splicing, muscle specification, and cell cycle checkpoint control as well as genes with serine/threonine kinase and helicase activity. Using a new program named AltAnalyze (http://www.AltAnalyze.org), we identified novel changes in protein domain and microRNA binding site architecture that were predicted to affect protein function and expression. These included an enrichment of splice isoforms that oppose cell-cycle arrest in hESCs and that promote calcium signaling and cardiac development in cardiac precursors. By combining genome-wide predictions of alternative splicing with new functional annotations, our data suggest potential mechanisms that may influence lineage commitment and hESC maintenance at the level of specific splice isoforms and microRNA regulation.