Release Notes
     
          REMBRANDT  Version 1.5 / webGenome Version 2.3
                         January 26, 2007
 
        National Cancer Institute Center for Bioinformatics
 
 
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                             Contents
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     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
 
 
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               1.0 Introduction and background
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    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
 
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                            2.0 Features
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    =====================
    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
 
 
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                   3.0 Known Issues/Future considerations
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     --  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
  
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                   4.0 Bug Reports and Support
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     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.
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                   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.

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                         6.0 NCICB resources
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     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