UNLABELLED: We present a Cytoscape plugin called Mosaic to support interactive network annotation, partitioning, layout and coloring based on gene ontology or other relevant annotations. AVAILABILITY: Mosaic is distributed for free under the Apache v2.0 open source license and can be downloaded via the Cytoscape plugin manager. A detailed user manual is available on the Mosaic web site (http://nrnb.org/tools/mosaic).

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/.

BACKGROUND: Leishmaniasis is a virulent parasitic infection that causes a worldwide disease burden. Most treatments have toxic side-effects and efficacy has decreased due to the emergence of resistant strains. The outlook is worsened by the absence of promising drug targets for this disease. We have taken a computational approach to the detection of new drug targets, which may become an effective strategy for the discovery of new drugs for this tropical disease. RESULTS: We have predicted the protein interaction network of Leishmania major by using three validated methods: PSIMAP, PEIMAP, and iPfam. Combining the results from these methods, we calculated a high confidence network (confidence score > 0.70) with 1,366 nodes and 33,861 interactions. We were able to predict the biological process for 263 interacting proteins by doing enrichment analysis of the clusters detected. Analyzing the topology of the network with metrics such as connectivity and betweenness centrality, we detected 142 potential drug targets after homology filtering with the human proteome. Further experiments can be done to validate these targets. CONCLUSION: We have constructed the first protein interaction network of the Leishmania major parasite by using a computational approach. The topological analysis of the protein network enabled us to identify a set of candidate proteins that may be both (1) essential for parasite survival and (2) without human orthologs. These potential targets are promising for further experimental validation. This strategy, if validated, may augment established drug discovery methodologies, for this and possibly other tropical diseases, with a relatively low additional investment of time and resources.

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.

SUMMARY: Cytoscape enhanced search plugin (ESP) enables searching complex biological networks on multiple attribute fields using logical operators and wildcards. Queries use an intuitive syntax and simple search line interface. ESP is implemented as a Cytoscape plugin and complements existing search functions in the Cytoscape network visualization and analysis software, allowing users to easily identify nodes, edges and subgraphs of interest, even for very large networks. Availabiity: http://chianti.ucsd.edu/cyto_web/plugins/ CONTACT: [email protected].

SUMMARY: VistaClara is a plug-in for Cytoscape which provides a more flexible means to visualize gene and protein expression within a network context. An extended attribute browser is provided in the form of a graphical and interactive permutation matrix that resembles the heat map displays popular in gene-expression analysis. This extended browser permits a variety of display options and interactions not currently available in Cytoscape. AVAILABILITY: http://chianti.ucsd.edu/cyto_web/plugins/index.php.

MOTIVATIONS: Technological advances in biomedical research are generating a plethora of heterogeneous data at a high rate. There is a critical need for extraction, integration and management tools for information discovery and synthesis from these heterogeneous data. RESULTS: In this paper, we present a general architecture, called ALFA, for information extraction and representation from diverse biological data. The ALFA architecture consists of: (i) a networked, hierarchical, hyper-graph object model for representing information from heterogeneous data sources in a standardized, structured format; and (ii) a suite of integrated, interactive software tools for information extraction and representation from diverse biological data sources. As part of our research efforts to explore this space, we have currently prototyped the ALFA object model and a set of interactive software tools for searching, filtering, and extracting information from scientific text. In particular, we describe BioFerret, a meta-search tool for searching and filtering relevant information from the web, and ALFA Text Viewer, an interactive tool for user-guided extraction, disambiguation, and representation of information from scientific text. We further demonstrate the potential of our tools in integrating the extracted information with experimental data and diagrammatic biological models via the common underlying ALFA representation. CONTACT: [email protected].

The main task of molecular biologists seeking to understand the molecular basis of disease is identifying and interpreting the relationships of genes, proteins, and pathways in living organisms. While emerging technologies have provided powerful analysis tools to this end, they have also produced an explosion of data, which biologists need to make sense of. We have built software tools to support the synthesis activities of molecular biologists, in particular the activities of organizing, retrieving, using, sharing, and reusing diverse biological information. A key aspect of our approach, based upon the findings of user studies, is the use of narrative structure as a conceptual framework for developing and representing the "story" of how genes, proteins, and other molecules interact in biological processes. Biological stories are represented both textually and graphically within a simple conceptual model of items, collections, and stories.

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'.

The field of molecular biology is in a remarkably rapid period of change, as the genome sequencing projects and new experimental technologies have generated an explosion of data. To analyze and draw insights from the vast amounts of information, biologists use a new generation of bioinformatics software tools, often working closely with mathematicians and computer scientists. There are elements of both collision and convergence in these interdisciplinary encounters. We conducted user studies with biologists engaged in investigating the molecular basis of disease. We describe several issues that arise in this collision/convergence of disciplines, drawing on the notion of boundary objects in-the-making. We provide recommendations on building technology for people whose work now sits at the crossroads of diverse and rapidly changing scientific fields.

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.

Growing usage and diversity of applications on the Internet makes Quality of Service (QoS) increasingly critical [15]. To date, the majority of research on QoS is systems oriented, focusing on traffic analysis, scheduling, and routing. Relatively minor attention has been paid to user-level QoS issues. It is not yet known how objective system quality relates to users' subjective perceptions of quality. This paper presents the results of quantitative experiments that establish a mapping between objective and perceived QoS in the context of Internet commerce. We also conducted focus groups to determine how contextual factors influence users' perceptions of QoS. We show that, while users' perceptions of World Wide Web QoS are influenced by a number of contextual factors, it is possible to correlate objective measures of QoS with subjective judgements made by users, and therefore influence system design. We argue that only by integrating users' requirements for QoS into system design can the utility of the future Internet be maximized.

FotoFile is an experimental system for multimedia organization and retrieval, based upon the design goal of making multimedia content accessible to non-expert users. Search and retrieval are done in terms that are natural to the task. The system blends human and automatic annotation methods. It extends textual search, browsing, and retrieval technologies to support multimedia data types.

This paper describes the conceptual model of Strudel, a toolkit of generic components for conversation and action management. To empower work groups to more effectively conduct their computer-based communication, coordination, and information sharing activities, Strudel packages within a simple model of task and action the semi-structured message, active message and conversation management paradigms. To facilitate acceptance and use within varying work cultures, we define this model in terms of a set of extensible components, which are implemented as a prototype software toolkit that is efficient, portable, customizable, and extensible. Issues considered briefly in this paper include threading in conversations that are converging or multi-party, and interoperability between active message systems.