Ultimately, the cell is not a flat list of subnetworks or gene clusters, it is a multi-scale hierarchical structure. This structure is well described by the Gene Ontology, the essential gold standard reference of gene function nearly everyone in the field uses. The Gene Ontology is manually-curated by experts which has not scaled well.
Welcome screen: easy access to data for users
From a user perspective, the benefits of v3.0 include…And the current disadvantages we have yet to overcome…
Rintaro’s Nature Methods paper is the first of its kind survey of Cytoscape plugins. Defines transition point to 3.0 and App Store.
Specific collaboration projects from Sander group
The NRNB NetworkPeople = blue circlesProjects = gold diamondsPublications = green trianglesNRNB funded = red borderThere are 315 nodes and 404 connections in the network. NRNB funds 41 (13%) of these nodes, which make 217 (54%) of the connections.
If you remove NRNB from this network… chaos…and wasted potential
A prominent feature of our collaboration network is GSoC: this summer we mentored 16 GSoC students (largest class yet). Leveraging $80,000 from Google!NRNB.org traffic increases 7-fold during GSoC application week. Averaged over the entire year, it is 4x more popular than any other page on our site.
The next most popular page is our Training Page, which lists upcoming Training events, Courses and TutorialsNext is the annual NetBio SIG meeting we organize in conjunction with ISMB each year. We just got accepted by ISMB to host for a 3rd year in a row. We are getting great speakers and impressive attendance for this meeting.Also high on the list is our Tools Gallery, which now includes screenshots and citation info. Over the last year, we added Cytoscape Web, WikiPathways and cBio Cancer Portal to the list of NRNB-supported tools.5,000 pageviews/week (cytoscape.org: 15,000 pv/wk)New paradigm for finding functionality in CytoscapeTagged navigation; user ranking and reviewsOne-click installAssisted app submission, including support for apps that export their own APIs for other apps to develop off of!First Cytoscape App Competition – helped get new apps in before 3.0 release – Winner will be announced on Friday during the Cytoscape App Expo
NRNB EAC Meeting 2012
National Resource for Network BiologyExternal Advisory Council (EAC) Meeting Wednesday December 12, 2012
Overview Technology Software Collabs Outreach PlansNRNB Overview• An NIGMS Biomedical Technology Resource Center focused on Network Biology• Research and develop new bioinformatic technologies to enable the use of biological networks (molecular, genetic, and social) among NIH-funded investigators• Collaborate directly with biological and clinical users to push the envelope of network analysis capabilities• Distribute open-source network technologies to the greater scientific community• Stimulate a portfolio of educational and outreach opportunities surrounding network biology
Overview Technology Software Collabs Outreach PlansNRNB Investigators Trey Ideker, PhD Principal Investigator, NRNB Gary Bader, PhD Departments of Medicine and Bioengineering Assistant Professor, Terrence Donnelly Centre University of California, San Diego for Cellular & Biomolecular Research Dr. Ideker uses genome-scale measurements to University of Toronto construct network models of DNA damage Dr. Bader works on biological network analysis response and cancer. He was the 2009 recipient and pathway information resources. of the Overton Prize from the International Society for Computational Biology. James Fowler, PhD Alex Pico, PhD Associate Professor, CalIT2 Center for Wireless & Executive Director, NRNB Population Health Systems and Political Science Gladstone Institute of Cardiovascular Disease University of California, San Diego Staff Research Scientist Dr. Fowler’s research concerns social networks, University of California, San Francisco behavioral economics, evolutionary game theory, Dr. Pico develops software tools and resources and genopolitics (the study of the genetic basis of that help analyze, visualize and explore political behavior). His research on social networks biomedical data in the context of these networks has been featured in Time’s Year in Medicine. Chris Sander, PhD Chair, Computational Biology Center, Benno Schwikowski, PhD Tri-Institutional Professor Chef du Laboratoire/Group Leader Memorial Sloan-Kettering Cancer Center Pasteur Institute Dr. Sander’s research focuses on Computational Dr. Schwikowski’s expertise lies in and Systems Biology of molecules, pathways, and combinatorial algorithms for Computational processes. and Systems Biology.
The National Resource for Network Biology: Integrating genomes & networks to understand health & disease NIH NCRR / NIGMS P41 GM103504 Draft Network Assembly Patient genotypeGenome sequencing Phenotype Disease diagnosis Response to therapy/drug Side effects Developmental outcome 1) How to assemble and visualize Rate of aging, etc.Gene expression & network models of the cell? other large scale molecular state measurements 2) How to use networks in healthcare?
Overview Technology Software Collabs Outreach PlansNRNB statistics ‘at-a-glance’Year 3 of 5 funded years, $700,000 per year direct + $175,000 supplement4 technology projects with matched driving biology20 NRNB-supported publications since start of fundingCytoscape used in ~250 pubs / year and has supported ~1400 NIH grants96 collaborations with NIH-funded investigators (60 new this year)27 training events over 7 countries, 32 academic courses by NRNB staff16 Google Summer of Code Students = $80,000 invested by GoogleRepresentative Publications:Dutkowski et al. A gene ontology inferred from molecular networks. Nature Biotech. (2013) [cover]Rügheimer et al. Applications of Intelligent Data Analysis for the Discovery of Gene RegulatoryNetworks. Computational Intelligence in Intelligent Data Analysis (2013)R Saito et al. A travel guide to Cytoscape plugins. Nature Methods (2012)Cerami et al. The cBio Cancer Genomics Portal. Cancer Discovery (2012)Morris, S. et al. ClusterMaker: multi-algorithm clustering for Cytoscape. BMC Bioinformatics (2011)Ideker, T. et al. Boosting signal-to-noise in complex biology: prior knowledge is power. Cell (2011)Dutkowski et al. Protein networks as logic functions in development and cancer. PLoS Comp Bio (2011).Fowler et al. Correlated genotypes in friendship networks. PNAS (2011)Bandyopadhyay and Ideker. Integrated Systems Biology [Poster], Nature Genetics (2010)
Overview Technology Software Collabs Outreach Plans Canadian Institutes of Health Research, 23 NICHD, 22 Others, 127 NIDA, 25 Wellcome Trust, 29 NINDS, 39 NIGMS, 354 NIMH, 47 NLM, 54 NHGRI, 58 NIEHS, 62 NCI, 205 NIDDK, 88 NHLBI, 88 NCRR, 110 NIAID, 103 Use of Cytoscape by grantees. We have identified >1,400 grants acknowledged in publications citing a Cytoscape paper (Shannon P et al. 2003; Cline MS et al. 2007; Smoot ME et al. 2011). One pie slice represents the number of grants from a particular agency. NIH institutes are represented by standard abbreviations.
Overview Technology Software Collabs Outreach PlansResponse to previous EAC critiques• Clearly articulate the link between funding and progress See previous chart; all described work is directly funded by NRNB• Focus not only on network visualization but on network-based analysis and decision making Exciting progress has been made for using networks as diagnostic biomarkers under TRD A• Encourage increased citation of Cytoscape Refactored Cytoscape.org to encourage citation; perform systematic literature tracking• Better track Cytoscape plugins and leverage developers Developed new Appstore (apps.cytoscape.org)• Track use of Cytoscape in the classroom Identified 32 courses using Cytoscape in 2011 - 2012
Overview Technology Software Collabs Outreach PlansAgenda• Progress on Technology Research & Dev.• Release of Cytoscape 3.0• Review of Collaboration and Service Projects• Progress on Training and Outreach• Plans for NRNB moving forward• Generate discussion and seek advice on all aspects
Overview Technology Software Collabs Outreach Plans Networks (in various states of curation) Circuits Coupled w/ Decision Tree Logic (or somatic mutation) Patient Expression TRD A: Protein networks as biomarkers of disease Ideker groupJanusz Dutkowski et al PLoS Comp Bio 2011
Overview Technology Software Collabs Outreach Plans TRD A: cBio Cancer Genomics Portal (Chris Sander / MSKCC) http://www.cbioportal.org• Make Cancer Genomics data available to a broad audience: – “Wet lab” biologists involved in functional studies. – Computational biologists• Allow quick access to small data slices (few genes, subset of samples)• Facilitate explorative data analysis / hypothesis generation and testing Cerami et al. 2012, Cancer Discovery
Overview Technology Software Collabs Outreach PlansCerami et al 2010, Nucl Acids Res
Overview Technology Software Collabs Outreach Plans Features for the network view Targeted-drugs Suggesting new targeted-drugs Direct targets (Released) indirect targets (work in progress) Targeted-drug Pathway data data Tumor data Infer and suggest novel, drug-based therapy optionsSources: DrugBank, KEGG Drugs, Cancer.gov e.g. AKT inhibitor for PTEN deletion
Overview Technology Software Collabs Outreach PlansTRD B: Using Cytoscape for Social Network ResearchSocial network of the Hadza hunter-gatherers of Tanzania. This analysis in Cytoscapereproduces the results published earlier this year in Nature by Fowler et al., whichshow a strong social network-dependence on the donation of public goods across andwithin groups. The histogram plot is based on the correlation values calculated byCyNetworkSignificance on the original and randomized networks.
Overview Technology Software Collabs Outreach PlansTRD C: Network Visualization and Representation (Pico / Bader)Visualizing Complex Networks as Ontology-Partitioned Mosaics Mosaic control panel, context menu and tiled result windows. The control panel shows both the color mapping legend and subnetwork display. Context menus for listed subnetworks allow the user to partition deeper within a given ontology branch.
Overview Technology Software Collabs Outreach PlansTRD D: Inference of Transcriptional Networks(Schwikowski group)• Create „fill-in-the-algorithm‟ infrastructure for inference of gene regulatory networks• Make methods accessible to biologists within the Cytoscape frameworkApproach: Create a software infrastructure (CYNI) for network inference algorithms
Overview Technology Software Collabs Outreach PlansSince the last EAC meeting – Summary-C design prototype-Hired engineer Oriol Guitart-Pla (02/15/12)-Working CYNI App-Documented API-User and CYNI App writer documentation-Additional CYNI functionality: Discretization and Imputation-Implemented and documented downloadable “Hello Worldexamples”-CYNI App presented at two French network biology meetings-CYNI App and Comprehensive documentation publiclyavailable
Overview Technology Software Collabs Outreach PlansCytoscape 3.0 Progress(Core NRNB Software)Major update of technology behind CytoscapeCreates a fully modular architecture and APICytoscape 2.x would not support the featuresneeded for the current vision of networkanalysis, e.g. scripting, multiple and 3Drenderers, crowd-sourcing, interoperability withweb and other tools
Overview Technology Software Collabs Outreach Plans- Cytoscape 2.x: Maintenance Releases - 2.8.2: Bug fixes and Improved memory allocation - 2.8.3: Bug fixes and better trackpad support for Mac platforms- Cytoscape 3 - 3.0.0 M5: June 2012: For developers - 3.0.0-Beta1: 10/9/2012: First Release for Users - 3.0.0 Final: This Week
Overview Technology Software Collabs Outreach PlansCytoscape 3.0 Advantages:Feature BeneficiaryWelcome screen New users (for solicitousness), existing users (for convenience)Import network Experienced users (for ease of use)Edge bend visual property Paper and presentation writersEdge bundling Users of high degree networksNetwork annotations Users of hierarchical networksEnhanced search Users of highly populated networksShow All in Table Browser Users with highly annotated networksMultiple network management All usersDisadvantages:• Unproven stability (i.e., likely numerous bugs)• Slow startup (4 times longer than v2.8)• Fewer plugins (though the missing plugins are the less popular ones)• Larger memory footprint leaves less room (especially on WinXP) for networks 31