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NRNB Annual Report 2016: Overall

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The overall component of our 2016 RPPR annual report for NRNB

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NRNB Annual Report 2016: Overall

  1. 1. NRNB  Annual  Report  2016  -­‐-­‐  Overall   B.1:  Specific  aims   The mission of the National Resource for Network Biology is to advance the science of Biological Networks by providing leading-edge bioinformatic methods, software and infrastructure, and by engaging the scientific community in a portfolio of collaboration and training opportunities. Biomedical research is increasingly dependent on knowledge of biological networks of multiple types and scales, including gene, protein and drug interactions, cell-cell and cell-host communication, and vast social networks. NRNB technologies enable researchers to assemble and analyze these networks and to use them to better understand biological systems and, in particular, how they fail in disease. NRNB has been funded as an NIGMS Biomedical Technology Research Resource since 2010. Our overall mission is accomplished through the following five Specific Aims: Specific Aim 1. To mount aggressive programs of research in cutting-edge bioinformatic technology to address major challenges and opportunities in Network Biology. In past years, we introduced a series of innovative methods including network- based biomarkers and network-based stratification of genomes. In the next support period, we will research approaches to represent and analyze network architecture across conditions or times; a general engine for genotype-to-phenotype prediction using network knowledge; and a platform to crowd-source construction of a gene ontology based wholly on network data from the community. Research proceeds in frequent communication with Driving Biomedical Projects, which provide data and applications from the labs of our close collaborators. Specific Aim 2. To catalyze phase transitions in how biological networks are represented and used in biomedical research. We are well-positioned to catalyze change along three complementary themes: I. Moving from static network data and models to networks that are differential or dynamic, II. Moving from networks that are primarily descriptive to those that are predictive of a range of phenotypes and behaviors, and III. Moving from flat networks (lists of pairwise interactions) to multi- scale representations that capture the hierarchy of modules comprising a biological system and reflected in its data. Specific Aim 3. To establish and disseminate robust end-user software, databases and high- performance computing infrastructure that enable network analysis and visualization methods for a broad biomedical research community. We will further develop the popular Cytoscape desktop application and App Store database of network analysis tools into a mature platform for network-based research on the web and in the cloud, to be called the Cytoscape Cyberinfrastructure. We will grow the collection of supported network tools distributed through nrnb.org. And we will update and expand the current NRNB computing hardware to keep pace with the growing size of network datasets and computing tasks. Specific Aim 4. To engage with leading biomedical investigators in productive collaborations
  2. 2. uniquely enabled by NRNB methods and tools. Since our inception in 2010, the NRNB has maintained an active and rolling portfolio of approximately 60-80 Collaborative and Service Projects. We will use best practices learned during this initial period of support to continue to acquire, triage, and/or complete collaborative projects, with an increasing focus on deploying new network methodologies developed under the three major technology themes outlined in Aim 2. Specific Aim 5. To train the current and next-generation of biomedical investigators in the science of Network Biology and its applications in disease research. The NRNB runs a highly attended annual network biology symposium, which starting in 2014 is planned jointly with DREAM and ICSB/RECOMB. We run a broad collection of network biology workshops and training events, including a very popular Google Summer Of Code program which over the past 4 years has recruited over 50 mentors and 100 students around the world to work on network biology projects under matching support from Google. B.2:  What  was  accomplished   Highlights  from  the  past  year  include:     • 103 publications citing NRNB grant • 800 citations of Cytoscape publications • 100s of users and dozens of developers trained on Cytoscape by NRNB staff • 428 members in our Network Biology LinkedIn group • 1750 members and 4200 messages on our two Google groups for Cytoscape • 9000 visits per week to Cytoscape.org • 14,000 downloads per month for Cytoscape • 3700 Cytoscape application launches per day • 42,000 page views in January 2016 for the Cytoscape App Store, and 580 downloads per day • The top 4 of 5 Google search results for "network biology tools" are all NRNB site pages. It is even in the top 10 results (#6 today) when searching for just "network biology". These are global, non-personalized results. • A total of 17 tools supported by NRNB • 48 active and pending collaborations with external investigators on diverse topics • 5 students trained at NRNB Academy last year • 20 NRNB coordinated training events in 6 countries • 71,000 unique sessions at Open Tutorials, 60% from new visitors • 26 open access Cytoscape app articles edited for F1000Research channel Technology  Research  and  Development   We launched three themes of technology research and development in our first year of renewed support for the NRNB. Progress on the first theme of Differential Networks includes work on optimization of network inference parameters for more accurate models of perturbations (i.e., high-throughput drug response data) of biological systems. We performed drug-target network analysis in our DBP 7 to identify upregulated targets in liposarcoma cell lines in response to a CDK4 inhibitor. We also continued to develop protein-protein interaction network alignment algorithms. And we implemented new tools in Cytoscape for working with mass spec data to facilitate future differential network
  3. 3. analysis. This work was shared with our DBP 1, the Krogan lab, from which we continue to collect valuable end-user input to design and prioritize our tool development. The second theme of Descriptive to Predictive Networks saw progress on two specific sub-aims. We developed a new machine learning method that uses patient similarity networks as features to predict disease outcome and successfully applied it to the prediction of Autism Spectrum Disorder phenotype from germ line DNA. We also continued to refine our network-based stratification approach to classifying subtypes of cancers, applying it most recently to newly available data from the Pan-Cancer Analysis of Whole Genomes. The next steps in this projects, as described in B.6, will provide a new resource for network analysis of drug response as proposed by Pommier, DBP 8. Progress on the third theme of Multi-scale Networks includes the development of a general progressive procedure, Active Interaction Mapping, which was used to assemble a comprehensive ontology of functions for autophagy. This work continues to be motivated by the data and prediction challenges in DBP 3 and 4, Mike Cherry (GO) and TCGA projects. We have also begun experimenting with using single cell RNA-seq data to improve the resolution of inferred cell-cell interaction networks. These are being applied to cancer stem cell biology and regenerative medicine. This work is being driven by Dr. Zandstra’s sustained interest in both inter-cellular networks and cell fate regulation, DBP 9. Collaboration  and  Service  Projects   NRNB staff have initiated 48 collaboration and service projects over the reporting period. A summary table is provided in the CSP component report, along with summaries of major project from each of the four sites led by the co-PIs. In broad strokes, the projects span online integration of network technology and knowledge bases, development of Cytoscape apps and cytoscape.js enhancements, co-author networks in drug development, customized one-on-one training sessions, and pathway and network analysis of hematopoietic and leukemic stem cells, AML, IL-7 pathways, lipid signaling, gliobastoma, musculoskeletal tumors, ophthalmopathy, HIV, breast cancer, head and neck cancer, ovarian cancer, and prostate cancer. Infrastructure   We have created the initial technologies needed to create an ecosystem of biologically valuable Internet-based services that exchange network data in a stable, performant, scalable, reusable, recombinable, and reliable manner. These include the CX network transfer format, CyWidgets of encapsulated web application library code, and a scalable service router called Elsa. During this period we have launched our Future of Publishing initiative, which envisions web-based journal publishers to make dynamic content available with their articles. As a pilot, Elsevier has leveraged the web-based cytoscape.js rendering library to add interactive networks to their ScienceDirect articles when authors supply Cytoscape network files (e.g., http://www.sciencedirect.com/science/article/pii/S2352340915000724). Since March 2014, we have built the NRNB Cluster, deployed eight high throughput computational workstations, laptops and desktop PCs, and deployed a VMware server farm. Papers resulting from cluster usage are listed in section B.5 of the Infrastructure report. Over the last year, 90% of the NRNB cluster nodes have been saturated with NRNB-sponsored jobs 90% of the time.
  4. 4. Dissemination   NRNB.org is the main web site for the National Resource for Network Biology and serves as the primary source of disseminating NRNB resources and associated information. It is constantly updated with information for NRNB collaborators and researchers as well as the larger network biology community. The site includes our project description and annual reports, available tools and resources, links to training materials, programs and events, and instruction in how to collaborate. The attentive maintenance and updating of the site helps make the top 4 of 5 Google search results for "network biology tools" all NRNB site pages. It is even in the top 10 results (#6 today) when searching for just "network biology". These are global, non-personalized results. Over the past year, traffic to the site averages about 850 visits per month. Since the site went live in late 2010, we have had over 73,000 visits. Since our last report (March 2014), we significantly reorganized the look of the cytoscape.org web site, added new pages to support users and developers, and upgraded the Download page to streamline the Cytoscape download process. We also added pages to advertise available Cytoscape-related jobs, a development vision and roadmap, statistics on many facets of Cytoscape usage, and a new Troubleshooting page. Statistics on Cytoscape downloads by version, Cytoscape.org visits, launches of Cytoscape sessions by users, and citations of Cytoscape and associated funding agencies are all provided in the Dissemination report. During this period, the Cytoscape App Store, which was created as an NRNB supplement project, continues to serve as the major source of dissemination for Cytoscape apps and related documentation. The App Store hosts over 260 apps developed by 588 different developers around the world. Cytoscape users download an average of 580 apps per day over the past 12 months. That has accumulated to just over 400,000 app downloads. During the month of January 2016, the site received over 42,000 page views. Graphs of app submissions, site visits and referral sources are all provided in the Dissemination report. NRNB staff members are responsible for maintaining these additional sources of dissemination: • Three Cytoscape mailing lists: helpdesk, discuss and cytostaff • Cytoscape competitions: http://nrnb.org/competition-2016.html • Open Tutorials: http://opentutorials.cgl.ucsf.edu/index.php/Main_Page • Cytoscape Publications Tumblr: http://cytoscape-publications.tumblr.com/ • Network Biology Publications Tumblr: http://netbiopub.tumblr.com/ • LinkedIn Network Biology Group: https://www.linkedin.com/groups/5123610 • F1000Research Cytoscape App Channel: http://f1000research.com/channels/cytoscapeapps • NRNB Academy SS 2015: http://www.nrnb.org/gsoc.html Training   The Training Coordinator, Dr. Morris, conducts the majority of training events for NRNB tool users and potential developers. We also leverage the fact that we are a multi-site resource and are thus able to host local training events on 4 different campuses. We also provide materials, training and advertising for events presented by non-NRNB staff. The Training report includes a table of 20 events coordinated by the NRNB, including courses, workshops, clubs and lectures in 6 countries.
  5. 5. New in this proposal, is an effort to train and consult for Bioinformatics Core personnel at research institutions to leverage their unique positions interfacing with a broad, ever- changing set of research projects. We are piloting this effort locally at UCSD and Gladstone Institutes via Drs. Ideker and Pico, respectively. For the first time since establishing NRNB Academy, we ran a special Summer Session in 2015 where we successfully mentored 4 students, out of a pool of 13 applicants. Our 2015 end-of-year report for NRNB Academy Summer Session can be found here: http://nrnb.org/gsoc-reports.html. We have received and abundance of testimonials from students and mentors, a subset of which are available on our website: http://nrnb.org/testimonials.html#collab-tab. B.4:  What  training  opportunities   Our collaboration and service projects during this period included many requests to prepare a custom training events and one-on-one sessions (see Services in CSP report B.2. table). For example, a small workshop for performing network visualization and analysis of mass spec data in Cytoscape was prepared by Drs. Morris and Pico. The Bader group also offered support to local researchers by consulting meetings and one- on-one training sessions. Our Training effort leveraged the fact that we are a multi-site resource and are thus able to host local training events on 4 different campuses. We also provided materials, training and advertising for events presented by non-NRNB staff. The Training report includes a table of 20 events coordinated by the NRNB, including courses, workshops, clubs and lectures in 6 countries. B.5:  How  have  results  been  disseminated     Technology  Research  and  Development   Technology research and development results are routinely published (see C.1) and discrete software tools and resources are highlighted and distributed through the NRNB web site at http://www.nrnb.org/tools-wall.html.   Infrastructure   We routinely promote Cytoscape and other NRNB infrastructure advancements through publications and via the tools page on the nrnb.org web site. Publications citing Cytoscape continue to increase year over year, numbering 799 in 2015, a 14% increase over 2014. NRNB staff were involved in at least 15 publications using Cytoscape and results obtained on the NRNB cluster. These are listed in the Infrastructure report.   Training   All of the activities reported in the Training component are providing “training opportunities.” These are opportunities that in most cases would not exist without NRNB staff and support. Each year we provide 100’s of researchers an introduction to network biology concepts and Cytoscape usage. We also train dozens of programmers how to
  6. 6. write apps for Cytoscape to provide domain-specific functionality to the platform. These programs have been very successful so far. This is evident from the testimonials we collect via survey following each event: http://nrnb.org/testimonials.html#collab-tab. B.6:  What  you  plan  to  do  next   Technology  Research  and  Development   For the first theme of Differential Networks, we plan to undertake a comprehensive data mining effort to inform the parameterization of prior confidence scores to further improve the network inference scheme described in B.2 and the original grant research strategy. The network alignment work will take into account the evolution of domain and binding site changes. And we will continue to tackle the long list of improvements to Cytoscape prioritized for mass spec practitioners and use cases, such as semi-automated identifier mapping and a API for running external jobs from within Cytoscape. Work on the second theme of Descriptive to Predictive Networks will progress during the next period via the continued development of a comprehensive pathway enrichment analysis workflow in Cytoscape, linking to GeneMANIA. In the area of subtype classification based on networks, we consider the impact of integrating both coding and non-coding mutations versus coding alone, as well as network structure modifications, e.g., due to mutations in TF binding sites. Extending molecular network knowledge to include not only gene and protein interactions but also interactions involving regulatory elements, will provide a new resource for network analysis of drug responses. The third theme of Multi-scale Networks will see the application of our data-driven ontology construction methods to human biology and investigations into the mathematical functions that integrate information across the many layers of hierarchy from genotype to phenotype. We will also plan to continue to make improvements in the inference cell-cell interaction networks by including cell receptor-ligand interactions, and applying this technology to cancer stem cell biology and regenerative medicine.   Collaboration  and  Service  Projects   New CSP requests are coming in all the time. We will continue to evaluate these per site as we have. New to this renewal, however, is the approach being tested by Gladstone and UCSD sites to have their respective Bioinformatics core facilities explicitly offer NRNB services as part of their regularly advertised campus services. Both groups have already seen many projects funnel in through this mechanism. We will continue to evaluate this approach and scale it where appropriate. See the CSP report for a more detailed description of specific projects on the horizon at each site.   Infrastructure   The overall goals for the Cytoscape Desktop are published on the Cytoscape Roadmap web page (http://cytoscape.org/roadmap.html). The Infrastructure report summarizes these and goes into detail on future Cytoscape Cyberinfrastructure and NRNB Cluster work plans. We also plan to adapt the Cytoscape App Store over the next reporting period to enable support for the Cytoscape Cyberinfrastructure (CI). Through the CI Store, application
  7. 7. programmers will be able to discover the existence, purpose, documentation, and API interface for services available for either immediate use or installation on private servers.   Training   New training materials, continued stream of training events and an upgraded GSoC effort are in the works for the next reporting period. We were just recently notified that we have been accepted to present an Introduction to Cytoscape workshop at the upcoming ISMB meeting in Orlando, Florida. This is a major conference in bioinformatics and systems biology. The conference includes the Network Biology community of special interest (COSI), which we started as NRNB representatives 5 years ago. We expect a good turn out for this training event, with a high rate of adoption and follow-up activity. So, for the next reporting period, we plan to overhaul our Introduction to Cytoscape materials and make some critical improvements. We also just recently submitted our application for GSoC 2016. If accepted, this should be one of our largest years yet. We have more mentors and more project ideas than prior years and are organizing a more coordinated outreach effort with a Student Outreach Packet that we will distribute to all NRNB mentors to help them contact and communicate with various student bodies that are likely to have the skill and interest to participate in GSoC 2016. C.2:  Website(s)  or  other  internet  site(s)   NRNB.org   NRNB.org is the main web site for the National Resource for Network Biology and serves as the primary source of disseminating NRNB resources and associated information. It has information for NRNB collaborators and researchers as well as the larger network biology community. The site includes our project description and annual reports, available tools and resources, links to training materials, programs and events, and instruction in how to collaborate. Over the past year, traffic to the site averages about 850 visits per month. Since the site went live in late 2010, we have had over 73,000 visits.   Cytoscape.org   As detailed in the Dissemination report, cytoscape.org has been significantly reorganized since our last progress report. New jobs, roadmap and usage content has been added to the site, as well as upgrades to the troubleshooting and download pages. As measured by Google Analytics, visits to the cytoscape.org web site have increased markedly year over year. Visits to cytoscape.org now number almost 1.5M since the site was created in 2012. And Cytoscape is being started approximately 3,500 times during weekdays throughout the world, and over 1,000 times during the weekends and holidays. This is nearly double the volume measured in 2014. Finally, the frequency of which Cytoscape is cited in papers indexed in PubMed continues to increase year over year, as shown below. The citation rate increase between 2014 and 2015 is 14%.
  8. 8.   Cytoscape  App  Store     A highlight of NRNB Dissemination efforts is the Cytoscape App Store (http://apps.cytoscape.org/), which was developed under supplemental funding to the main NRNB award. The goals of the App Store are to highlight the important features that apps add to Cytoscape, to enable researchers to find and install apps they need, and for developers to promote their apps. It has stimulated a sizable community of Cytoscape App developers, hosting over 260 apps developed by 588 different developers around the world. Cytoscape users download an average of 580 apps per day over the past 12 months. That has accumulated to just over 400,000 app downloads. The average submission rate remains between 2 and 3 new apps per month. During the month of January 2016, the site received over 42,000 page views. As shown below, there have been 335,340 visits since the store was staged in mid 2012 – an average of 11 visitors per hour, with year-over-year visits continuing to increase. Associated graphs are available in the Dissemination report.   OpenTutorials   Open Tutorials (http://opentutorials.cgl.ucsf.edu/index.php/Main_Page) is the main source for tutorial materials for Cytoscape and other NRNB tools, and is being used both internally by presenters, and by researchers and developers. The site now hosts 6 detailed user tutorials and 3 developer tutorials. Traffic to Open Tutorials is consistent, with over 71,000 unique sessions in the last year, a slight increase over the previous year.   Others   As detailed in Administrative, Dissemination and Training reports, we also maintain a handful of other sites related to NRNB activities, including • Network Biology LinkedIn group • Tumblr feeds for Network Biology- and Cytoscape-related publications • Special pages for GSoC and NRNB Academy • Special pages for annual NetBio SIG conference • Cytoscape competition events and results • Guest editor roles for F1000Research Channel for Cytoscape Apps • New Cytoscape App Developer Ladder • New site for hosting a dynamically generated manual for Cytoscape C.3:  New  technologies  and  techniques   TRD  1.1   The discussed improvement to the perturbation biology methodology is a significant technology that has been publicly shared via publication. Additionally, there is an accompanying web application (http://www.sanderlab.org/pertbio/) that is available. Users can explore the data from the analysis and download models produced by the analysis.
  9. 9.   TRD  1.2   As mentioned in sections B.2 and B.6, our major new technologies are progressing in all three TRDs. We are particularly excited about our precision medicine patient network results which we hope will translate into applications in a wider set of diseases in 2016.   TRD  1.3   The new network import dialog as described and pictured in B.2. is being shared through the free, open source distribution of Cytoscape 3.3.0+ as of December 2015. The new stringApp for Cytoscape as described and pictured in B.2. is being shared as a free, open source app distributed through the Cytoscape App Store as of December 2015.   TRD  2.1   As mentioned in sections B.2 and B.6, our major new technologies are progressing in all three TRDs. We are particularly excited about our precision medicine patient network results which we hope will translate into applications in a wider set of diseases in 2016.   TRD  2.2   We anticipate that several useful resources will be generated by the proposed research. First, the new NBS pipeline for non-coding mutations will be released and explained in detail in our manuscript. The mutation islands, as well as their annotation, the eQTL and HiC based networks, and the patient subtypes uncovered by NBS, will also be available. The code used in this study will be deposited on GitHub along with tutorial documentation.   TRD  3.2   Active Interaction Mapping technique. This technique allows the value of new interaction mapping efforts to be rigorously evaluated rather than assumed, and the design of these experiments can be guided rationally, based on current knowledge and data. This technique will be publicly described in a manuscript which is currently under review.   TRD  3.3   As mentioned in sections B.2 and B.6, our major new technologies are progressing in all three TRDs. We are particularly excited about our precision medicine patient network results which we hope will translate into applications in a wider set of diseases in 2016.
  10. 10.   CSP  technologies  per  site:   Sander  Group   Several of the ongoing projects will make available analysis code and pipelines once completed; in some cases, this will be done as re-usable R packages. One focus in making projects publicly available is the development of web applications to help in the exploration of project data. Below are some technologies that are facilitating the development of these web applications: • SBGNViz.js: An reusable Javascript component that allows the visualization of detailed pathway information using SBGN in the SBGNML format, https://github.com/nrnb/sbgnviz-js • Shiny R Applications: One avenue for making a project publicly available is through the use of the Shiny R web framework (produced by the RStudio company) to quickly build web-based interfaces. This has been used by some Sander lab projects including the CCRCC Metabolomics Data Explorer (http://sanderlab.org/kidneyMetabProject/ related to a metabolomics project using kidney cancer cancer samples) that includes a novel metabologram view to highlight gene expression and metabolite changes across pathways. The development of web applications for projects is enhanced by embeddable, interactive components written in Javascript, such as SBGNViz.js; the possibility of reusing these components in Shiny web applications is also possible. This is demonstrated by the the r-cytoscape.js R package (https://github.com/cytoscape/r- cytoscape.js) that allows users to make use of cytoscape.js in Shiny web applications to display network data.   Bader  Group   Here below are listed two examples of additional features and application developments that the Bader group is planning to integrate in the gene-set analysis workflow: 1) AutoAnnotate application: EnrichmentMap creates a network of enriched gene-sets connected by overlapping genes. Similar pathways are organized in modules that represent a common biological function. AutoAnnotate uses ClusterMaker2 to automatically identify modules in a network, and uses WordCloud to create a label for each module by using the most frequent words associated with the node labels of each module. These automatic and unbiased labels help to quickly identify and visualize biological processes represented on the network map. 2) Implementation of 2 sided Mann-Whitney test for EnrichmentMap post-analysis: post- analysis is a feature of EnrichmentMap that enables the addition of a gene-set to an existing EnrichmentMap network. A typical use of a 2 sided Mann-Whitney test in post- analysis is to add a list or transcription factor of micro-RNA predicted targets as an additional gene-set and assess the level of overlap with genes in pathways : overlap with pathways enriched in up-regulated genes (1 side of the test) or enriched in down- regulated genes (the other side of the test).
  11. 11.   Pico  Group   Code produced during collaborations from this period: • New features to CentiScaPe app for Cytoscape, by Sakshi Pratap. CentiScaPe is a popular app for Cytoscape 3 for extensive graph analysis. This was a very successful project, with many new features added. Both mentor and student are excited to continue Cytoscape development year-round and plan to participate in participate in future GSoC summer programs. https://github.com/nrnb/nrnbacademy2015sakshi • Porting support for SBML model import and work in Cytoscape, by Matthias König. This app, which provides SBML import and functionality to Cytoscape was successfully completed and submitted to app store at the end of this summer, and already has 493 downloads! A publication is in the works for this project as well. https://github.com/nrnb/cy3sbml • SBGNViz.js: Cytoscape.js visualization of SBGN-ML diagrams, by Metin Can Siper. This project builds upon the cytoscape.js library to provide support for SBGN process description notation. Some of the constributions made to this project includes bug fixes, adding gui options, integrating a new cose layout, and releasing version 2.4.2. https://github.com/nrnb/sbgnviz-js • Adding PCA to clusterMaker2, by Vijay Dhameliya. This project adds principle component analysis to the successful clusterMaker2 app, which provides over a dozen cluster algorithms and interactive heatmap visualization. https://github.com/nrnb/clusterMaker2   Infrastructure  technologies:   Detailed in section C.3 of the Infrastructure report are the following technologies: • CX network interchange format • cyWidget system • Elsa request router C.5.a:  Other  products   TRD  3.2   A significantly faster version of the popular random forests regression algorithm in the Python scikit-learn package was created for this work and is publicly available on GitHub at https://github.com/michaelkyu/scikit-learn-fasterRF.
  12. 12. E.2:  Impact  on  technology  commercialization  or  public  use   TRD  1.3   The stringApp for Cytoscape impacts the accessibility of the STRING database for Cytoscape users. As as described and pictured in B.2, the app lets Cytoscape users directly query and import interactions, data and annotations from the STRING database.   Infrastructure   The cytoscape.org web site is served on a virtual machine that resides on the NRNB VMware server cluster. Cytoscape installers are staged on the standalone chianti.ucsd.edu server, which is also sponsored by the NRNB. The Cytoscape App Store is served on a virtual machine in the Jacobs School of Engineering server room at UC San Diego. The NRNB pays $50 per month for this virtual machine, and it will be transferred to NRNB servers once larger VMware servers are purchased. The NRNB Cluster has created a unique facility for the processing of genomic and network computations that require dbGaP-protected data as an integral part of the research of least 6 faculty, postdocs and graduate students. Additionally, general non- dbGaP computations directly enable the research of another 15 postdocs and graduate students that (because of their high processor and memory use) could not have been performed elsewhere as cost effectively. Overall, in the last year, 90% of the cluster nodes have been saturated with NRNB-sponsored jobs 90% of the time. Storage arrays have ranged between 80% and 90% full. The NRNB VMware server farm currently runs 15 virtual machines that implement security, database and file system services, and Cytoscape CI services for the NRNB. Executing these functions on either discrete servers or on public clouds could not have been performed more cost effectively.

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