Release Notes REMBRANDT Version 1.5 / webGenome Version 2.3 January 26, 2007 National Cancer Institute Center for Bioinformatics ===================================================================== Contents ===================================================================== 1.0 Introduction and background 2.0 Features 3.0 Known Issues/Future Considerations 4.0 Bug Reports and Support 5.0 Tutorials and help pages 6.0 NCICB Web resources ===================================================================== 1.0 Introduction and background ===================================================================== Rembrandt ===================== REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) is a robust bioinformatics knowledgebase framework that leverages data warehousing technology to host and integrate clinical and functional genomics data from clinical trials involving patients suffering from Gliomas. The knowledge framework will provide researchers with the ability to perform ad hoc querying and reporting across multiple data domains, such as Gene Expression, Chromosomal aberrations and Clinical data. Scientists will be able to answer basic questions related to a patient or patient population and view the integrated data sets in a variety of contexts. Tools that link data to other annotations such as cellular pathways, gene ontology terms and genomic information are embedded. REMBRANDT is a product of the NCI Center for Bioinformatics and its partners, specifically, the Neuro-Oncology branch, CCR (Center for Cancer Research), NCI and NINDS. Visit the REMBRANDT web site for more information: -- http://rembrandt.nci.nih.gov webGenome ===================== WebGenome is a web-based application for creating genomics plots of array-based data and genomic annotation. Version 2.3 provides a client plotting service to external applications, such as Rembrandt. Users must enter webGenome through redirection from another application; the only way to load data is by selecting it in the referring client application. Data types supported in this version include copy number (i.e., aCGH), loss of heterozygosity (LOH), and gene expression. Two basic types of plots can be generated: * Scatter Plots - Plots DNA copy number measurements across the genome, chromosome, or chromosomal interval. * Ideogram Plot - Shows chromosomal amplifications and deletions in relation to cytogenetic chromosome ideograms. The underlying data model used by webGenome is a very simplied version of the MAGE-OM. The most important concept for the use of the system is that individual array data sets, called bioassays are aggregated into experiments. Visit the following site URL for more information: http://caintegrator-info.nci.nih.gov/developers/#wgenome ===================================================================== 2.0 Features ===================================================================== ===================== Rembrandt v1.5 Features: ===================== -- F-Test added to Class Comparison: Select the F-test option to test a hypothesis of the means of two or more populations, the technique is called the Analysis of Variance (ANOVA). The ANOVA simplifies the Ftest, where F-test is the mean square for each main effect and the interaction effect divided by the within variance. A one-way ANOVA or single factor ANOVA tests differences between the groups classified only on one independent variable. -- 3D PCA applet: The three-dimensional Principal Component Analysis enables you to view PCA plot data in three dimensions. For more information about the PCA plot, see Principal Component Analysis Plot. The applet supports Java Plugin versions 1.4 -- BRB archieve file download: REMBRANDT enables you to download the BRB archive file and analyze data using BRB-ArrayTools created by the Biometric Research Branch of the National Cancer Institute. BRB-ArrayTools is a comprehensive state-of-the-art statistical analysis system for microarray gene expression data. It is free for non-commercial purposes and can be licensed for commercial purposes from the NIH. BRB-ArrayTools installs as an Excel plug-in using a self-installer. -- KEGG Browser: Easily add KEGG pathways to the query by using the KEGG browser to search and identify pathways of interest. -- List Management (upload, type, union, intersect, difference, export, validation, saving lists): The REMBRANDT Manage Lists function centralizes all activities pertaining to the creation and management of user-defined, as well as study-defined, PatientDID Lists, Gene Lists, and Reporters Lists. With these lists, you can further refine queries or facilitate analysis. -- Gene Expression Plot is now dynamically calculated using t-test. -- New help documentation: New context sensitive help has been added to each page of the application. -- Externalized annotation links: Links for all annotations are now configurable seperately from the web applications. These properties can be updated independently from the webapp. -- Clone IDs now map to LPG IMAGE Clone View (http://lpgws.nci.nih.gov/cgi-bin/iview.cgi) -- Box and whisker plot: The Box and Whisker Log2 Intensity Gene Expression Plot (Figure 3.4) displays a box plot without all the individual data points. A box and whisker plot or box plot is a graph that presents information from a five-number summary. -- Box and whisker-coin plot: A coin plot is box-and-whisker plot with all individual data points. This enables you to obtain a diagram representing a statistical summary of the data without the disadvantage of concealing the real data. -- Advanced queries now allow multiple disease selection -- Group vs group based KM plot: A K-M Survival Plot for Gene Expression Data displays the survival rate at each time point for samples in 2 compared custom lists of samples. -- Group based gene-ex/KM plot: Perform a Gene Expression Simple Search, using a custom patient list as a constraint. -- Registration/login new pages w/captcha: First-time REMBRANDT users need to register via the web-based form to obtain a username and password. -- Feedback form: The feedback questionnaire is an optional form which collects usage data from the user on logout. -- Re-run advanced queries from view results page (all possible views): All previously completed queries will appear in the View Results page, and can be directly ran from this page without going through the Refine Query page again. -- Color-less, Shape-less PCA plot: The ability to remove all colors and shapes from a PCA 2-D plot has been added to better demonstrate clustering. -- New User guide: New PDF user guide has been added for the 1.5 release. This guide provides information on every section of the application. -- New Tutorials: Updated Flash tutorials are available which highlight some of the new features in 1.5. -- Externalized cache: User cache (persisted session data) is now stored in an external location, independent from the web-app. -- HTTPS: REMBRANDT now uses HTTPS for enhanced security. -- New tech stack (jboss404): REMBRANDT leverages the most recent NCICB Tech Stack, including updated versions of JBOSS and the JDK. -- IE7 Support: REMBRANDT has been tested and verified on IE7 for windows. -- Enhanced logging: Revised logging statements will provide support for debugging the application. -- Multiple Cosmetic Bug Fixes and UI enhancements User can filter by Institution on Finalized page Upgraded caBIO pathway from caBIOv2.1 to caBIOv3.1 Complex queries from finalized page are saved and available during future sessions Upload user lists can now be saved and available during future sessions Users can now save samples where one or more rows are highlighted. “Check All” now selects All items on All report pages, not just the current page "Select Samples" is now a single click for PCA Now throughout the HOA, selection of groups is by double click On PCA plots, Non-tumor samples do not display survival length shapes, but are now designated as Non-Tumor Bug Fix: Mouse over on bar graph now displays p-value instead of fold change Bug Fix: Disease sub-types in advanced search for GE Analysis Bug Fix: Fixed bug associated with filter for p-value on the class comparison result page Bug Fix: You can access user guide and tutorials from within the application Bug Fix: Associated with Advance Option on Class Comparison and PCA -- The following previous known issues have now been resolved in this release Bug Fix: -- WebGenome plots are supported only on IE browser (6.0 and above) and not on Safari and Firefox Bug Fix: -- Safari users will see "localized string not found" for the Gene and Clone ID browse buttons. Bug Fix: -- In Safari, a user can not unselect the IMAGE Id check box. Bug Fix: -- In Safari, a user can not uncheck the Clone Id/Probe Set Id check box. Bug Fix: -- On query pages, clicking on the "clear" button does not clear the query after the user has previewed the report from that query ===================== WebGenome version 2.3 Features: ===================== WebGenome version 2.3 provides support for LOH data and includes additional features requested by users including: -- Analytic operations have been decoupled from plot generation. This results in better performance as the same operations are not performed each time there is a change in plot parameters. -- A workspace feature has been added. All data uploaded or generated by an analytic are saved in this workspace. Additionally, generated plots are also saved in the workspace. -- Plotting parameters changes are made in a context sensitive popup window available from the plotting page. Only those parameters that apply to the plot type are provided. -- Users can change the display name of uploaded experiments and bioassays in the workspace. -- Users can set the color of bioassays in the workspace. -- Plots now use PNG (portable network graphics) instead of SVG (scalable vector graphics). -- New analytic operations have been added including minimum common altered region and aCGH based smoothing. (See http://www.bioconductor.org/repository/release1.5/package/html/aCGH.html for more information.) -- Test Plot generation is available by default on the home page. These plots are created using randomly generated data. -- Help documentation updated ===================== Rembrandt v1.0 Features: ===================== -- Added ability to perform higher-order integrative analysis of clinical and genomic datasets Users can perform PCA, Hierarchical clustering and class comparison analysis at runtime. -- Integrated Rembrandt application with webGenome to visualize chromosomal abnormality data in scatter and ideogram plots -- Implemented Rembrandt authentication using Common Security Module. -- Implemented query inbox for realtime status checking on compute-intensive analysis queries -- Enhanced reporting capabilities with new links to reporter annotations -- Added the ability to persist user results (samples and genes of interest) across sessions -- Support for more clinical data elements (Therapy, clinical evaluation parameters etc) on the clinical query page -- Implemented graphical display for analyzed datasets: 2-D PCA chart, Hierarchical cluster dendrogram, clinical plots with the ability to select samples and save them for future use in queries -- Implemented unified gene algorithm for affymetrix gene expression data to allow for gene-based querying in Quick search (Gene expression and Kaplan-Meier Survival plot) ===================== Rembrandt v0.51 Features: ===================== -- Added the ability to look for gene expression and copy number data for "All Genes" (All Genes usecase) for further analysis of saved result sets -- Added project results set saving and querying using a step-based workflow process, -- Reports distinguish between a missing value and a value that did not match the criteria in the presentation pages for cDNA array data. -- Added a Kaplan-Meier survival (KM) line plot for "intermediate" samples which were not included in the up regulated and down regulated in the KM graphics. -- Added a Sample Criteria to Clinical query that will allow users to browse in biospecimen IDS -- Added log-rank p-Value for various groups in KM survival plots -- Allows entire Chromosome, or p, q arm search for each chromosome -- Enabled multiple report pages - window spawning -- Added pathway annotation to report -- Implemented previous "Gene Symbol" look-up strategy for HUGO gene symbols -- Added caching mechanism to reports, thus allowing for visualization and comparison between reports at a later stage within a given session -- Added various filtering, highlighting and pagination mechanisms to report pages to enhance usability ===================== Rembrandt v0.50 Features: ===================== -- Plot gene expression profiles across different tumor types for a gene of interest -- Gene Expression and Copy Number Kaplan-Meier (K-M) survival plot for a gene of interest. Dynamically change the fold change and amplification and deletion thresholds to redraw the graph. -- Search gene expression differential fold change for Glioma samples (in comparison to non-tumor samples) from two platforms (Affymetrix and home-grown cDNA array) -- Search copy number (chromosomal aberration) data for Glioma samples from Affymetrix 100K SNP array platform -- Search basic clinical data such as tumor sub-types, age at diagnosis of patient, Gender, Survival -- Search criteria for Gene expression data include Gene symbol (available also as batch upload), Genbank Accession, Locuslink ID, Probeset ID, IMAGE ID, Pathway name, GO ID, Chromosomal region (Cytoband, bp start/end), Array platform, Tumor type and fold change threshold -- Search criteria for copy number data include Gene symbol (available also as batch upload), Genbank Accession, Locuslink ID, SNP Probeset ID, dbSNP ID,Chromosomal region (Cytoband, bp start/end), Tumor type and amplification/deletion threshold -- Perform combinatorial queries from different domains using "and/or" operands -- Select report of interest (Clinical report, Gene expression/ Copy number reports) from a context-sensitive report menu -- Download reports with annotations into a tab-delimited file format -- View online tutorials and context sensitive online help throughout the application ===================================================================== 3.0 Known Issues/Future considerations ===================================================================== -- WebGenome plots may timeout when number of samples exceeds 200 -- WebGenome plots from "All Genes" Copy Number query does not work. -- WebGenome plots interactivity do not function correctly with the Safari browser on the Macintosh operating environment. Plots can still be generated correctly using Safari, but mouse-over and tooltip interaction do not function. This issue is primarily caused by Safari's inadequate JavaScript implementation/support. To obtain full plot interactivity using the Macintosh OS, users are recommended to use the Firefox browser - which works correctly. -- On class comparison page, for t test and wilcoxin test, p-value for the same reporters is different when the comparison and baseline groups are swapped. P values are the same until E-10 value. -- On the GeneExpression, Box & Whisker plot, "Mouse over" max and min values are maximum and minimum regular (non-outlier) values, they are not the maximum and minimum outlier values. -- On the three-dimensional Principal Component Analysis applet, the button for "copy the data to the clipboard" does not function. -- Copying and pasting the URL into a new browser from the application while in the middle of a query, generates an error -- Cytoband drop down list is not in order on create query pages. -- In Safari, nothing shows up in the cytoband dropdown list. Workaround: Search base pair position first, then come back and search cytoband again -- Currently no scientific validation of the cytoband and base pair positions of a chromosome. User has to go look for the correct map location in the NCBI map viewer and then select the cytoband of interest -- User cannot get pathway information and GO ID's in generated reports, but can see them in the excel downloads from reports ===================================================================== 4.0 Bug Reports and Support ===================================================================== For Rembrandt: Send email to ncicb@pop.nci.nih.gov to request support or report a bug. Please put "REMBRANDT" in the subject line. Clicking on the feedback button on the application login page will open your default email system to send feedback to Rembrandt UAT (User Acceptance Test) list serv For WebGenome: Send email to dhall@rti.org to request support or report a bug. Please put "webGenome Support" in the subject line for support. Please put "webGenome Bug" in the subject line when reporting a bug. ===================================================================== 5.0 Tutorials and help pages ===================================================================== REMRBANDT tutorials can be viewed from the application home page. Go to http://rembrandt-db.nci.nih.gov and click on "tutorials" Context-sensitive Online help is available throughout the application. Click on the "?" help button to view online help WebGenome test plots can be generated from the webGenome home page using randomly generated data. Users may interact with the test plots using the Work Area to change the initial plots. Help information is available from all webGenome pages. ===================================================================== 6.0 NCICB resources ===================================================================== The NCI Center for Bioinformatics -- http://ncicb.nci.nih.gov/ Cancer Biomedical Informatics Grid -- https://cabig.nci.nih.gov NCICB Application Support -- http://ncicbsupport.nci.nih.gov/sw/ REMBRANDT Application -- https://caintegrator.nci.nih.gov/rembrandt/ Rembrandt informational website -- http://caintegrator-info.nci.nih.gov/rembrandt caIntegrator informational website -- http://caintegrator-info.nci.nih.gov caArray -- http://caarray.nci.nih.gov Clinical Trials -- http://trials.nci.nih.gov/ //end