geWorkbench

Multi t-test

Multi_t_test

Removed from MINDy tutorial because in fact we do not check these parameter files in the aracne version used in mindy

Advanced - setting ARACNe dataset parameters

MINDy makes use of the original Fixed Bandwidth implementation of ARACNe. This algorithm can make use of parameters which are data set specific, if available (by separate calculation), and which can be used in setting the Kernel Width and Threshold. ARACNe includes default values with which to calculate these parameters, which also depend on the number of arrays in the dataset. However, it is possible to use the newer version of ARACNe (also called ARACNe2), which is included in geWorkbench as a separate component, to calculate the needed values for a particular dataset. The key is that ARACNe looks for two parameter files with the fitted parameters, and will use these if they are found. The files are called "config_kernel.txt" and "config_threshold.txt". If you want to use custom parameters in MINDy, you must create these two files by using a separate PREPROCESSING run of ARACNe on your dataset.

Running ARACNe in PREPROCESSING mode, with algorithm FIXED_BANDWIDTH, will create two files in the geWorkbench root directory, named according to the following template:

• DatasetName_ARACNe_FBW_kernel.txt
• DatasetName_ARACNe_FBW_threshold.txt

where "DatasetName" is the name of the microrarray dataset for which you ran ARACNe. For example, for the Bcell-100.exp dataset, the following two files would be generated:

• Bcell-100.exp_ARACNe_FBW_kernel.txt
• Bcell-100.exp_ARACNe_FBW_threshold.txt

To make these file available to MINDy, just rename them to "config_kernel.txt" and "config_threshold.txt".

Note that these default file names will be seen and the contents used by all versions of ARACNe, both standalone and within MINDy. So you should remove or rename these files before doing any other work with ARACNe/MINDy.

Removed from MINDy tutorial because DPI not used

DPI settings (Not used in MINDy)

The Data Processing Inequality (triangle inequality) can be used to remove the effects of indirect interactions, e.g. if TF1->TF2->Target, the DPI can be used to remove the indirect action of TF1 on the target. Stated another way, the DPI can be used to remove the weakest interaction of those between any three markers. Setting the DPI Tolerance is independent of whether a DPI Target List is used.

DPI Target List (Not used in MINDy)

The DPI target list can be used to limit the ARACNE calculation to transcriptional networks. It is used to screen out spurious regulatory interaction signals of genes that are tightly coexpressed but are not in a regulatory relationship to each other, for example genes for proteins that are used to build a protein complex. The eukaryotic ribosome, for example, needs the stoichiometric expression of about 80 proteins, but those proteins are not in a regulatory relationship to each other.

• The specified markers will be given preferential treatment during the DPI edge-removal step. Edges originating from markers on this list will not be removed by edges originating from markers not on this list. However, for DPI calculations where all three markers are members of the list, the weakest connecting edge may still be removed.

• If used, it is suggested that the DPI Target List should contain all markers that are annotated as transcription factors. Signaling proteins could also be included.

• A comma-separated list of markers can be typed in to the text field, or it can be loaded from an external file.

DPI Tolerance (Not used in MINDy)

The DPI tolerance specifies the degree of MI sampling error to be accepted, as with a finite sample size an exact value MI cannot be calculated.

• The DPI tolerance is normally set between 0 and 0.15, since values larger than 0.15 yield higher false positives.
• See the ARACNe tutorial page and Margolin et al. 2006 for further details on use of DPI.

Retired geWorkbench tutorial pages

These links are to components no longer part of geWorkbench - just in case they come back someday.

Reverse Engineering |

http://wiki.c2b2.columbia.edu/workbench/index.php/Tutorial_-_Reverse_Engineering

Network Browser |

http://wiki.c2b2.columbia.edu/workbench/index.php/Tutorial_-_Network_Browser

Synteny may come back some day but does not seem to be under active development:

Synteny |

http://wiki.c2b2.columbia.edu/workbench/index.php/Tutorial_-_Synteny

Notes from Bernd on Tutorials, plus responses.

5/9/2006:T-Test

Comments on:

http://www.geworkbench.org/workbench/index.php/Tutorial_-_Differential_Expression

All in all nothing much to complain, great example (i.e. it is working for me and I understood, at least I think so)

• Where is the Multi T Test sample?

KCS RESPONSE - I have added a multi-t-test example.

• A reference for the T-test would be nice.

KCS RESPONSE - I have added a web-site link to a description of the t-test.

• Why is it “T Test” and not “T-test” or something else? (it just looks strange, but I don’t know what is right)

KCS RESPONSE - I have at least made it t-Test or t-test now. It is still a bit inconsistent.

T Test analysis identifies markers with statistically significant differential expression between two sets of microarrays. The t-test (T Test???) determines for each marker if there is a significant difference between the two groups (case and control). To perform this analysis, you must classify the panels(sets of microarrays) as “case” and “control”, set the analysis parameters and view the results in the visualization components. A detailed description of the T Test parameters is described in the online help.

• I don’t have “Gene Panel” but rather “Marker” for the results.

KCS RESPONSE - fixed.

• The label to the right displays the Significance value (the lower the value, the more likely different) and gene name for the displayed genes. The genes are displayed in ascending order by Significance Value.

KCS RESPONSE - please restate this as a question.

• Pat, Abs, Ratio Overlapping Pages Icon: Not the T Test display. => why italic? For me they don’t do anything, does it mean they shouldn’t be there?

KCS RESPONSE - no, they don't seem to do much. I have taken out the extraneous text.

As to the functionality:

1. Gene height and gene width can take negative values, this is a bug! (Color Mosaic)
2. Pat, Abs, etc don’t do anything (see above)
3. Marking a gene in the Markers panel doesn’t do anything in the Volcano Plot.
4. I can only zoom into the plot, but not mark any spots in either of the visualization panels

5/9/2006: Clustering

Comments on:

http://www.geworkbench.org/workbench/index.php/Tutorial_-_Clustering

• I guess you know that the data set is not available for download ;-)

KCS RESPONSE - it is there now (as of a few weeks ago now).

• "Go to the Analysis component, and select Fast Hierarchical Clustering Analysis"
  • I believe there should be somewhere something said about the algorithm used for fast hierarchical clustering. Not all parameters are self explanatory.

KCS RESPONSE - there is a little problem with the algorithm right now....

• Should the check box called “enable zoom” or maybe “enable selection”? I think it might be kind of confusing this way.

KCS RESPONSE - good point, it is not really a zoom is it? I have entered this into Mantis.

And after this nice tutorial I am left with the question: And now what? Or, why did I do this, again?

KCS RESPONSE - I have added a bit of context at the beginning....

5/10/2006:Basics

Comments on:

http://www.geworkbench.org/workbench/index.php/Tutorial_-_Basics

• The Data Management area can hold one workspace, and a workspace in turn can hold one or more projects. Projects can be used as wished {remove} to group different data sets. Each opened data file or analysis result is stored in a project [This is not really clear. Especially I would like to know something about the general concept of merging files vs. not merging files]. A workspace with all the data [what about the state of the data, especially what happened to like analyzing the data and its results?] it contains can be saved and returned to later.

• The GUI provides a menu bar at top with a standard choice of commands. Many commands that are available in the menu bar are also available by right-clicking on data objects.

That is not entirely true. Usually you have an exit function under File, which is missing

In general I would like to see some more details on the Project/File concept as eluded on earlier. I think this is a good place to put this information and I haven’t seen it anywhere else

RESPONSE by KCS - I have added a section about data representation which introduces files and merging. There is another section of the tutorials called Projects and Data Files which describes some of the mechanics.

5/10/2006: Project and Data Files

Comments on:

http://www.geworkbench.org/workbench/index.php/Tutorial_-_Projects_and_Data_File

KCS - These responses were added 6/2/2006.

• Affymetrix File Matrix - this is the native file type created by geWorkbench
  • I actually don’t know how to create this file from geWorkbench…

KCS - I have added more about merging....

• By the way you when we were talking about Matlab you said you only support free software: What about Affymetrix??? Are Genepix RMA Express free as well???

KCS - Affymetrix is our primary data source. Matlab is an analysis program that we do not have ourselves.

• What are Pattern Files?
• What are Genotypic data Files (should be files not Files, same for FASTA Files and Pattern Files and others)

• We select the 10 MAS5 format text files from the directory geworkbench\data\training\cardiogenomics.med.harvard.edu, which is included in the geWorkbench download as shown in the picture below.

• I don’t get the message that you show

KCS - you probably had already loaded a file of that type, so its definition did not need to be reloaded.

• The merged dataset is listed in the Project folder. The data is displayed, in single array format, in the Microarray Viewer. Note we have increased the intensity slider to maximum here.
  • Here you should mention that you only see the first/last array and that you can scroll through the arrays with the array slider

KCS - I have added this.

• There are no Okay buttons, but rather OK

KCS - fixed.

• I mentioned this somewhere else already: When you want to delete/remove a bunch of data nodes you can select them, right click them, but only one file is then removed = BUG!

KCS - You should add this to Mantis.

• Ah, now I see how you can save your special geWorkbench file. Maybe you should mention here that this is actually saving the data in this particular format. (At least I assume it does so)

KCS - added more explanatory text.

• For the remote upload: The difference between Open and Go is not clear to me. Here is THE place for me where I am missing the mouse over help messages.

KCS - added explanatory text.

• The first image is not correct. For me it doesn’t show all the array experiments

KCS - The image is correct as far as I know...

• It is totally NON intuitive to have to right-click on a remote dataset to get additional information. It was at first not even obvious that there is additional data available…

KCS - I completely agree, this is the oddest thing....

• It is interesting that you chose this example, because it seems that only four or so of all the entries actually have derived assays. ;-)

KCS - not by chance....

• Maybe you want to explain what derived assays are?

KCS - Added....

• Also for the remote source, I would like to know what other sources are there and how the interface should look like. I have no clue what and why and how I should link other sources.

KCS - there are actually no other sources. This is for future reference.

• Maybe this is another place to put some more information about merging files…

KCS - another mention of merging has been added.

5/10/2006: Data subset

Comments on:

http://www.geworkbench.org/workbench/index.php/Tutorial_-_Data_Subsets

• I would like to see a reference to the paper/web page where you took your example from. This way the interested reader can get some insights into the biological question…

KCS RESPONSE - I have added this info to the Tutorial_-_Data page.

• I don’t think you the Activate/Deactivate functions under the right mouse click.

KCS RESPONSE - Activate/Deactivate work for me.

5/10/2006: remote data

Are you sure that the remote data function is working correctly. I seam to have trouble loading some of the data… KCS - RESPONSE 6/5/2006 - I can load caArray data normally

5/10/2006: Viewing microarray dataset

Comments on

http://www.geworkbench.org/workbench/index.php/Tutorial_-_Viewing_a_Microarray_Dataset

• in the visualization panel I don’t think the alignment of properties and corresponding names is ideal, but that is just optical

KCS RESPONSE - I don't understand the comment - what exactly are you refering too?

• Why does it say “+ Intensity”?

KCS RESPONSE - If you stretch out the display horizontally a bit, you will see the color-code bar appear, which shows the color spectrum from - to + expression maxima. It is probably a bug that this disappears when screen real-estate gets tight.... I have entered it into Mantis.

• Why is there a bluish bar underneath the slider of Intensity?

KCS RESPONSE - I think it is for esthetics.

• When removing object, maybe the delete button should do the same thing

KCS RESPONSE - The same thing as what? I don't understand the comment.

• The images created (right click, image snapshot) can be saved and exported (File-> export).

• When analyzing sets of arrays, wouldn’t it be helpful to have a mean/median function over all spots at specific positions. This way systematic errors can be detected.

KCS RESPONSE - I am not sure what you mean. We should discuss this in person.

• Expression Profiles: This is a line graph of gene[s] expression profiles across several arrays/ hybridizations. [space] Each marker is a separate color line.

KCS RESPONSE - rewrote section.

• Scatter Plot: A pairwise (array vs. array and marker vs. marker) comparison and plotting of expression values. [One array servers as the reference (x-axis serves, set by right-clicking and selecting x-axis, dark background) and subsequent arrays are plotted against this reference in different sub images. Up to six sub images can be created.]

KCS RESPONSE - changes incorporated.

• Genepix Value Computation: You can specify how to compute the value displayed for a Genepix array. The default setting is Option (Mean F635 - Mean B635) / (Mean F532 - Mean B532).

KCS RESPONSE - corrected.

• I don’t know anything about Genepix, but I assume that everyone playing around with geWorkbench and microarrays would know this, right?
• Select Relative for the visualization preference. Note that this choice will not take effect until the next time you load a data set.
  • I would consider this as a bug!

KCS RESPONSE - I don't know why this is so, you can enter it as an enhancement request.

Great page!

5/10/2006: Filtering and Normalization

Comments on:

http://www.geworkbench.org/workbench/index.php/Tutorial_-_Filtering_and_Normalizing

KCS RESPONSE - all corrections/suggestions below were acted on. The page was mostly rewritten, and all new screenshots supplied. The detailed example 1 was added, which explains how the normalized and filtered data set used in many of the other tutorials was created.

Affy Detection Call

Applicable to Affymetrix data only. Sets all measurements whose detection status is any user-defined combination of A, P or M as missing.

• are you sure that everyone knows A, P, or M?

4. Choose the maximum number of arrays that can have missing values before a/the marker is removed – default is 0.

• Somehow I have difficulties to understand what is going on, but that can be me or my sleepyness…

Normalizers:

AS you know, I don’t much about micro array analysis, but from what I understood from my friends, is that normalization is a BIG issue. So I would guess that there should be done much more on this front. When the starting data is not optimal you can’t expect much from later analysis. Therefore I would make this a high priority.

• You haven’t mentioned the quantile Normalizer in the list of normalizers. What about houseKeeping Genes Normalizer

• It is either missing value computation (as in my program) or missing value calculation (web-page)

5/11/2006: Marker Annotations

Comments on:

http://wiki.c2b2.columbia.edu/workbench/index.php/Tutorial_-_Marker_Annotations

1. The desired marker set is activated by checking its box in the Marker Sets component.

=> This should be explained in more detail. It took me some time to figure out what you meant.

KCS - I added a link to a picture of selecting markers in the Markers component.

Otherwise everything is straight forward.

There is much you can do here. It would be good if you could incorporate some of the information into geWorkbench for further analysis. Of the top of my head I can think about retrieving sequence for alignments, combining pathway information: which common elements are within the pathways my array/experiment came up with etc…

This obviously needs some further thoughts and discussions.

KCS - some of this is actually already in place, but more can be done....

5/11/2006:; Sequence Retrieval

Comments on:

http://wiki.c2b2.columbia.edu/workbench/index.php/Tutorial_-_Sequence_Retrieval

You forgot to mention that you have to add the sequence to the project, they are not automatically imported.

KCS RESPONSE - added description of how to add sequences to a project.

When playing with the sequence features, I realized that the distinction between the visualization panel and the analysis panel is not clear enough.

KCS RESPONSE - I have added a bit more explanation to differentiate these.

There is no scroll bar for the sequences = BUG!!

KCS RESPONSE - There is a vertical scrollbar when needed. Not sure what the problem is here.

The squence that is displayed should be marked in the window, otherwise it has no meaning.

KCS RESPONSE - this should be entered as an enhancement request.

I saw some stretches of “EEEEEEEEEEEEEEEEEEEEEE” are those correct, never saw them in NCBI.

KCS RESPONSE - this is an error. The cached data is itself corrupt. We are going to switch to Santa Cruz to get data live.

Where do the promoters in the Promoter panel come from? Where are they located on the sequence?

KCS RESPONSE - not pertinent to this panel. The list is derived from Jasper. The Promoter component will search the motifs against sequences.

Is the length of the squence normalized? I believe that the line in the visual panel represents the sequence, but why are the all the same length?

KCS RESPONSE - they are all the same length because 4000 bp was retrieved for each.

Is this the squence from the array or the sequence from the associated gene/ predicted associated gene?

KCS RESPONSE - these are sequences +- the gene transcription start site.

When using the analysis try to modify the vertical size of the panel: You will see that the BLAST/STOP buttons disapear pretty soon and it look awkward what is happening there.

KCS RESPONSE - I don't see this problem in the Sequence Analysis component.

How long does BLAST run, but I guess this belongs in the next page.

5/11/2006: Blast

Comments on:

http://wiki.c2b2.columbia.edu/workbench/index.php/Tutorial_-_BLAST

I don’t think it is a good idea to put the advanced options on a separate page next to all the other tools. Does this mean that those advanced options are also for HMM etc?

KCS RESPONSE - No, they disappear when HMM is selected.

Service is now called Server_Info

KCS RESPONSE - you must have an older version of the program

I don’t have the NCBI option.

KCS RESPONSE - you must have an older version of the program

Also the All Markers and total sequence number is not displayed.

KCS RESPONSE - you must have an older version of the program

There is no Main tab

KCS RESPONSE - you must have an older version of the program

You can mouse over the result set to see how many sequences are in it

• I can’t

KCS RESPONSE - you must have an older version of the program

The “Add Selected Sequence to Project” button looks more like an editable field than a button. Somehow the colors seem weird.

KCS RESPONSE - you must have an older version of the program  

The selected sequence show up on the same level as the target sequence, is this correct? What if I have several Blast searches and select from all of them some sequences?

KCS RESPONSE - yes, sequences put back in the project are at the top level. You cannot operate on more than one Blast result set at once, so I don't understand the second question.

I can’t combine the sequence into a dataset

KCS RESPONSE - It is true, there is no merge function for sequencs. This could be a feature request.

In the pane at left in the picture below, the name of the input query sequence is shown.

ð what do you mean?

KCS RESPONSE - e.g. the gi number. Will clarify on page. Note that the "gi" is not displayed, just the number. This is a bug. It may be have been reported already, as I already knew about this. will check.

It would be probably nice to be able to sort the output table by the description or name etc

KCS RESPONSE - this is a definite feature request. It should absolutely be implemented.

The part of the window with the actual alignment should show the beginning of the alignment not the end = BUG

KCS RESPONSE - This was already fixed in version 1.03.

All in all I don’t think this is solved in an optimal way…

KCS RESPONSE - oh well.....

It seems that you were using an older/other version of geWorkbench for the web tutorial….

5/11/2006: Pattern Discovery

Comments on

http://wiki.c2b2.columbia.edu/workbench/index.php/Tutorial_-_Pattern_Discovery

There is no ‘Create” button but rather the circular arrow that does the job.

KCS RESPONSE - The Create button is part of the session creation pane that appears after you hit the arrow. I have clarified this.

The server is not set with the default “splash.cu-genome.org”

KCS RESPONSE - I know.

Viewing all patterns can be VERY slow

KCS RESPONSE - best not to do that then.

There should be a link included to the paper describing SPLASH

KCS RESPONSE - added citation of 2000 SPLASH paper.

The result of the search can be viewed both in the Pattern Discovery module itself and in other sequence viewer modules such as "Sequence" and "Promoter".

• I can’t see the pattern in promoter
• in Sequence only ONE pattern can be selected at a time = BUG??
• it can be viewed only in the parent sequence (at least I hope)

KCS RESPONSE - This brings up a weird point - If you change the selected Project Folder object from Pattern Discovery (the returned hits)

1. The results still display
2. The other sequence panels appear
3. The Pattern Discovery results can be selected in the table and display in the Sequence, Promoter, and Position Histogram components.
4. The way it works is that if you select another sequence, the pattern discovery results are cleared. If you go back and select the original sequences you searched against, the pattern discovery is not restored. It is however restored if you select the Pattern Discovery object to force them to reload. They then remain in the component even when focus is changed to the sequences again.

Regarding the other points:

1. more than one pattern can be selected and displayed.
2. yes, patterns are only displayed in their parent sequences ( but what happens if they are reloaded?)
3. They are visible in the Promoter component.

What is the logical behavior here? Guess this is how it has to be done, shows problems with being too clever.

It seems that tool is actually quite interesting. It would be good to be able to use these patterns to search for additional sequences that have this pattern, for example in all the up regulated sequences from a micro array experiment.

I have tried “Add patterns to Project” but I don’t think I was successful….

KCS RESPONSE - we need a description of each of the save options in the when you right-click on a pattern result. I also can't tell if "Add Pattern is working".

At some point the application became very slow to respond. I am not really sure why though.

5/15/2006: Promoter Analysis

Comments on:

http://wiki.c2b2.columbia.edu/workbench/index.php/Tutorial_-_Promoter_Analysis

The Promoter Component allows a set of sequences to be scanned by selected motifs of known transcription factor binding sites. These motifs are derived from the Jasper project. The motifs are in the form of PSSM - Position Specific Scoring Matrices. One or more of the motifs can be selected by double-clicking on them in the list box. The selected motif will be added to the search box just below. When the desired search [space] is ready, hit the scan button. The results of the search will be shown superimposed on lines representing the sequences just to the right. Hits from different TF motifs will be displayed in different colors.

Where can I find “clusterTree38_Sequences.fasta”?

When opening geWorkbench it should start with an empty project.

Why is the scanning so slow?

The names of the TFs should be color coded as well

Stop button doesn’t work

5/15/2006: Reverse Engineering

Comments on:

http://wiki.c2b2.columbia.edu/workbench/index.php/Tutorial_-_Reverse_Engineering

After the Mutual Information algorithm has been run, an adjacency matrix will be placed in the Projects Folder:

• you forgot to mention that running means “create network”

KCS RESPONSE - I had a couple of steps out of order which is now corrected and the process better explained.

switching to organic is COOL!!!

In Cytoscape the window cannot be changed by clicking on the panel heads, only by selecting the network name.

KCS RESPONSE - Wow, I didn't even ever notice those tabs. Bug report.

I don’t know if this should be corrected, but anyway: I accidentally resized a node in the graph. When switching back and forth between two networks the original size was restored. I didn’t find any other way to this, other by changing the size back manually, even remodeling the graph by doing another “organic” didn’t work…

KCS RESPONSE - This is a bug. Enter into Mantis.

With all the links to different browsers why not one to pubmed?

KCS RESPONSE - This is a feature request. Enter into Mantis.

What is the graph with Probability/Score for?

KCS RESPONSE - It appears to be broken. First reported 10 months ago.

5/15/2006: GO Term enrichment

Comments on:

http://wiki.c2b2.columbia.edu/workbench/index.php/Tutorial_-_GO_Term_Enrichment

building a tree is not really that fast….

And once it finished, I can’t execute the map lists again, I didn’t get any results

So I don’t really know what is going on…

Looking at the synteny tutorial, there is not much more to do… ;-)

6/2/2006: Sequence

1. When loading a sequence from GenBank the name of the sequence is the identifier from GenBank. I believe the name should not only be a number but there should be information that identifies the number as a GenBank id. E.g. gi_1234

KCS RESPONSE - reported as bug - I had long noticed this too..

1. It should be possible to select and copy portions of the sequence.

KCS RESPONSE - the fasta file can be opened in the editor. Selecting text in a graphic window is probably hard to do.

1. When resizing the window, the number of characters to be displayed is adjusted. This takes a lot of time, but looks kind of nice, too. I still think that this can be done faster

KCS RESPONSE - none.

1. In the parameters window the parameters are centered, this somehow looks awkward, but I can’t think of anything better, having it either on the top or bottom would create a large space underneath…
2. when double clicking on the line sequence, the View doesn’t change from Line to Full sequence even though the view changes as expected

KCS RESPONSE - bug entered.

1. After I removed a project the sequence is still there. It seems the sequence and the data associated with the project are not really destroyed.

KCS RESPONSE - this has already been reported as a bug.

1. Freeing memory seems not to be working

KCS RESPONSE - what is this one about????

1. I have loaded two sequences. The visual pane remembers which of (Promoter, Sequence, Position Histogram) panes is used for each sequence. But it doesn’t remember the individual options within those panes for each sequence. E.g. when I select the line view for one sequence and the Full sequence for the other, it will display the last selected viewing option.
2. How can I display two sequences in one window?

1. In line view the sequence is displayed in the lower section. In the description it says that the sequence is centered, but when I click on the line at a position 170 (show by the mouse over function) the sequence displayed is from 121-290.

KCS RESPONSE - bug reported as #664, similar to already reported bug 295.

1. After the pattern discovery, there is something wrong with the mouse-over function for the sequence position (this also happens with the regular sequence window): The sequence position is displayed in a box next to the mouse. This is true for the whole sub-window and not only around the sequence line. When dragging the mouse over the sequence on the bottom of the screen then the part right of the mouse is removed and never restored even after moving back in the upper window.

KCS RESPONSE - cannot interpret or reproduce, seems fine in current application.

1. After sequence patterns have been generated and one or more patterns have been selected not all marked regions are correct. I had problems with sequence patterns TTG.TTTT. Here the pattern is displayed in blue on top of the original sequence, making it almost impossible to read those sections.

KCS RESPONSE - looks good now...

1. with “All / Matching Patters” selected one has to double click the pattern to show the line display. Single click give a blank screen after I scrolled down in the pattern list.

KCS RESPONSE - don't understand this one, application looks ok to me....

1. the numeric positions are displayed every 40 characters and not every 20 as described in the use case.

KCS RESPONSE - use case to be altered.

1. left and right shift arrows are not present

KCS RESPONSE - they are now present.

NOTES

HistoneDB

The Histone Database: A Comprehensive Resource for Histones and Histone Fold-Containing Proteins Leonardo Marin˜ o-Ramı´rez,1 Benjamin Hsu,2 Andreas D. Baxevanis,2 and David Landsman1* PROTEINS: Structure, Function, and Bioinformatics 62:838–842 (2006) http://www.ncbi.nlm.nih.gov/CBBresearch/Marino/reprints/Proteins_838.pdf

http://research.nhgri.nih.gov/histones/web/complete.shtml

Outstanding Issues From Informatics [edit] User level problems

   * No undo
         o All changes destructive and irreversible
         o Nearly impossible to retrofit existing structure to support undo 
   * Confusing selection model
         o Difficult to tell what's selected / active - does it affect my current analysis?
         o No ability to have different components operate on different selections 
   * No repeatability of experiments
   * No workflow support
   * Confusing connection between components - what affects what? Where did my results go?
   * Large Memory footprint
         o Just the framework and component initialization, over 200 megs
         o Large overhead for data
         o Every datapoint stored as multiple objects
         o Means probably unable to load, let alone analyze mid to large sized datasets 
   * Performance problems
         o All components receive every event whether used or not, many components recompute something upon reception of those events - leads to poor interface responsiveness
         o Complex object structures cause unnecessary and large processing overhead for analyses
         o Roughly 10x speedup was gained by Hierarchical clustering in routing around data structures 
   * Lack of adequate data import export functionality
         o Most components should export to tab delimited text file at a minimum 
   * No built in standards or support for progress monitoring or cancellation of long running processes 

[edit] Developer level problems

   * Non-standard event system
         o Runtime extension model causes non-standard CGLib exceptions
         o Mid level Java developers not familiar with annotations 
   * Overwhelming and only semi-functional data object structure
         o Many objects extending Java Collections classes, but not fully implementing their interface contracts - leads to subtle and confusing errors 
   * Selection model confusing
         o Many objects maintaining their own internal selected data structures