NRNB EAC Meeting 2012

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Slides for NRNB EAC Meeting, December 2012

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  • Drug sources – suggest drugs
  • 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

    1. 1. National Resource for Network BiologyExternal Advisory Council (EAC) Meeting Wednesday December 12, 2012
    2. 2. 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
    3. 3. 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.
    4. 4. 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?
    5. 5. 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)
    6. 6. 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.
    7. 7. Overview Technology Software Collabs Outreach PlansNRNB Funding Allocation 1000 Supp-Crowdsourcing 900 Collaboration 800 Outreach Admin-Pico 700 Admin-Ideker 600 Admin-Asst. $1000s 500 Core Comp/Software TRD-A-Ideker 400 TRD-A-Sander 300 TRD-B-Fowler 200 TRD-C-Pico TRD-C-Bader 100 TRD-D-Schwikowski 0 Co-I Salaries Year 1 Year 2
    8. 8. 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
    9. 9. 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
    10. 10. Overview Technology Software Collabs Outreach PlansPico (UCSF)
    11. 11. 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
    12. 12. Overview Technology Software Collabs Outreach Plans TRD A: Network Biomarkers (Ideker); DBP 2 (Kipps) Publication: Chuang et al. Blood (2012) [cover article]
    13. 13. 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
    14. 14. Overview Technology Software Collabs Outreach PlansCerami et al 2010, Nucl Acids Res
    15. 15. 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
    16. 16. 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.
    17. 17. 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.
    18. 18. Overview Technology Software Collabs Outreach Plans • Annotation • Gene set analysis • Edge analysis • Module analysis
    19. 19. Overview Technology Software Collabs Outreach Plans
    20. 20. Overview Technology Software Collabs Outreach PlansTRD C: Network visualization and representation (Ideker) Introducing NeXO A Network eXtracted Ontology Janusz Dutkowski et al. Nature Biotechnology (2013)
    21. 21. Overview Technology Software Collabs Outreach Plans Assembly and alignment of anetwork-extracted gene ontology
    22. 22. Overview Technology Software Collabs Outreach Plans
    23. 23. Overview Technology Software Collabs Outreach Plans
    24. 24. 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
    25. 25. 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
    26. 26. Overview Technology Software Collabs Outreach Plans
    27. 27. Overview Technology Software Collabs Outreach Plans TRD Outreach Ideas
    28. 28. 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
    29. 29. 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
    30. 30. UBE2L3 RRM1 EDIL3 NFKB1 CTBP1 UBE2N POLR2A NME1 OTUB1 JAK1 Overview Technology Software Collabs Outreach Plans PARK2 KPNA1 DNMT1 LAT NF1 XRCC6 VCP EXO1 DNAH8 ENSG00000137337 H2AFX GPR3 SMAD4 HSD17B1P1 FANCD2 BLM STAT1 UBE2D3 WNT2B WWP2 FANCG CDC25C ECHDC1 ID4 ACACA PSAP PARP2 CHGB RCHY1 BRCC3 FBXL7 UIMC1 HERC2 ORC2L C17orf70 C11orf30 TOX3 CASP3 BUB1 9606.ENSP00000358154 XRCC3 ELK4 BIRC5 RNASEL MAP2K1 GSTP1 RNF2 MED17 TRRAP RARB CCNA2 CREBBP EP400 MSH2 NEK2 UBA1 ECT2 PGR GTF2F1 NEK10 YRDC GMNN ORC3L CDK13 DNAJA3 FBXW4 PLK3 HRAS ANTXR1 CDK1 FAM175A JUN FGF11 CDK8 SMARCB1 KRT14 HSPA8 FANCB FBXL3 GATA3 New Features for 3 DDB1 TSPAN17 ARIH1 CDC25A CDC45 PAX6 ELAC2 APLP2 CDKN1A EIF4G1 TOP3A PEG3 PTEN CHEK2 KPNA3 PPP1CA1 TUBB2A POU2F1 HIC1 CHGA CTCFL PML FLI1 MAP3K4 NUP153 DCAF11 EZH2 RNF31PIK3CA2 ERCC2 EGFR SMARCE1 RPA1 GTF2E1 AKAP10 NUSAP1 SMARCC2 FANCA MED21 RAD9A CDKN1B HMMR WRN MLH1 MRE11A ETS1 AP2B1 ESR1 TRIM28 UBE2I SMC1A XRCC5 RBL1 TSPAN9 NMI RNF144B SHFM1 ERCC1 RNF8 HSD17B1 SUGT1 •Edge Bundling WT1 UBC ELK1 RBMXL2 UBB AURKA JUND CNR1 CDK4 MELK PPP1R3A •Welcome Screen SUMO2 ERCC4 BRCA1 LMO7FBXO4 MDM2 PLK1 NBR1 •New Data Import Clients PMS1 IGF1R TOPBP1 TUBA4A UBA52 FBXO11 TAF2G •Network Annotations PPT1 CSTF1 SMARCA4 RNF168 JUNB TERF2 PPM1D DHFR •Network Collections BATF FBXL5 PALB2 CDK16 FBXO25 SMARCC1 SMARCD2 NCOA3 FAM175B BRCA1 •Enhanced Search MED24 STK11 MED13 PIAS1 WHSC2 CREB1 SMAD3 E2F4 RBBP7 CHD8 ERBB2 BRE HDAC2 WWP1 TP53 LMO4 •Cleaner API MAD2L1 FANCC KIAA1182 EP300 RAD17 BRAP CDK2 HYRC FANCE NUFIP1 PIAS4 DCUN1D1 HIST1H4A PMS2 RNF53 BARD1 •Experimental Headless Mode BRCC1 POLL RBBP8 FANCL CLSPN FGFR2 RFC1 BRCA1 CHTF18AT2A NBR2 MYC FANCF MAP4K4 SMAD1 TFDP2 GTF2H4 FBXO24 MAP3K3 DCLRE1C DDB2 BRIP1 RAD54B RBL2 RBBP4 BAP1RNF20 RAD51 DPPA3 AR MPP3 CHEK1 NFYA FBXO9 BUB1B ATF1 RNF11 ZCCHC8 C5orf4 PSMC3IP RPL31 TRAF7 RNF53 PRC1 RELA SCG2 NR1H2 SMURF2 MCM4 SUMO1 UBE3A TADA3 CCNB1 TUBGCP4 RND2 IFI27 INSC RAD51L3 USF2 RAD51C HOXA5 Brca1 TP53BP1 MKI67 COBRA1 TUBG1 FANCI LIG3 SPO11 CDH1 RAD50 TSC1 C19orf40 FBXO21 PCNA CDKN2A FHIT MNAT1 ZNF350 MED23 STAT3 KIF11 CYP17A1 SP1 C19orf62 ERCC3 GADD45A H2AFY DMC1 FBXO7 RASSF1 CSTF2 SRC SIRT1 RFC2 KPNA6 FHL2 ARNT ATRIP DLK1 RAD52 PARP1 EREG XRCC2 ASPM DPH1 BMI1 DHX9 ENSG00000204435 IFI16 AKT1 XPA POU4F1 WDR48 RPA2 CDKL4 MZT1 MSH6 CTCF 30 TIPARP HSD17B2 PIK3R1 GLI1 XRCC4 CCNE1 OPCML
    31. 31. 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
    32. 32. Overview Technology Software Collabs Outreach Plans TRD Outreach Ideas 32

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