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"AceDraw" is primarily a database management program which provides a Graphical User Interface (GUI) to facilitate data entry and visualization of data for the Human Genome Project.
The Human Genome Project is an international project led by the Sanger Center in the United Kingdom, and the National Institutes of Health in the United States. Its goal is to completely map out the human genome through DNA sequencing by the year 2005. As the human mitochondrial genome (16.6 kiloBasepairs long) has already been completely sequenced, the genome under investigation is the nuclear genome. The entire genome is about 3 billion base pairs long; each chromosome is on the order of hundreds of millions of base pairs in size. A base is one of the 4 nucleotides: adenine (A), cytosine (C), guanine (G), or thymine (T). In the helical structure of the DNA molecule, these bases come in pairs. Adenine is templated with thymine, and cytosine is complementary to guanine. This DNA sequence of A, T, G, or C (3 billion of them) can be translated into proteins. Each gene codes for one protein. There are about 65,000 - 80,000 genes in the human genome. The human genome is broken up into 24 different chromosomes, numbered 1- 22 plus the X and Y sex chromosomes. The AceDraw program has been designed for working with human chromosome 16, which is about 100 million base pairs long and is currently under investigation by Caltech's genome center. However, the program should work for other chromosomes as well.
The chromosome can be thought of as an extremely long and monotonous one-dimensional map, on which there are some landmarks (see below). Through a process called fluorescence in situ hybridization (also known as FISH), researchers are able to introduce fluorophore markers into some of the clones and allow them to hybridize with chromosomal DNA. Then it is relatively easy to look at the chromosome under ultraviolet radiation and see where fluorescent bits ended up. This provides at least a very general idea of where a clone fits into the chromosome. Bacterial Artificial Chromosomes (BACs), which were invented here at Caltech, are bacterial clones of human chromosome pieces. These clones may be as small as about 500 base pairs long, making sequencing them relatively easy. There are also very specific landmarks scattered (again, non-randomly) throughout the genome. These landmarks are called sequence tagged sites (also called STS markers). Most of these sites are unique sequences hundreds of base pairs long. That is to say, if you find this sequence, you are supposed to know where you are in the genome. There are about 30,000 of these STS sites.
The BAC clones and STS markers are fully represented in AceDraw. Each clone has its own catalog number, and has a set of data associated with it, for example, how long it is, how much of it has been sequenced (if at all), and what positive STS sites it contains, where it was placed by FISH mapping, etc. Likewise, the STS markers have catalog numbers, positions, and contain information about which BAC clones they contain. Using position information, these markers and clones are fully visualized with AceDraw.
The main window (see figure below) consists of the following sections from top to bottom: the pull-down menu bar, the whole-view chromosome display, the whole-view ruler, the locator for zooming into a specific region of the chromosome, the zoomed-view chromosome display, zoomed-view ruler display, STS marker sites, BAC clones display, and the bottom row of informational boxes displaying the name and position of a selected object.
2.1 Menu Bar
The menu bar consists of the following pull-down menus. All the menu items can also be accessed by hot keys as displayed in the right side of each menu item.
2.1.1 File Menu
The "File" menu (see figure below) contains the following menu items:
2.1.1.1 Parse .ace File
Parse user selected .ace File saved from AceDB program and insert parsed entries into the SQL database server. Note that current implementation does not allow parsed entries to appear immediately into the window. User needs to exit and restart the AceDraw program in order to visualize parsed data entries.
2.1.1.1.1 Parse Chrom Band
When selected, it brings up a file selection menu (see figure below) from which a .ace file may be selected. It only parses data related to chromosome bands from selected file and put parsed entries into the SQL database server.
2.1.1.1.2 Parse BAC
Only parses BAC clone entries from a .ace file selected through the file selection menu and put parsed entries into the SQL database server.
2.1.1.1.3 Parse YAC
Only parses YAC clone entries from a .ace file selected through the file selection menu and put parsed entries into the SQL database server.
2.1.1.1.4 Parse STS
Only parses STS marker entries from a .ace file selected through the file selection menu and put parsed entries into the SQL database server.
2.1.1.1.5 Parse All Above
When selected, it parses data entries related to all above (Chrom Band, BAC, YAC and STS) from the selected .ace file and put parsed data entries into the SQL database server.
2.1.1.2 Dump .ace File
Use this option (see figure below) to save data entries of interest (currently in the SQL database server) into a .ace file (in AceDB format) so that the saved .ace file can be read in by the AceDB program.
2.1.1.2.1 Dump Chrom Band
Save all of the chromosome band information currently in the SQL database server into a .ace file. When selected, it brings up a file selection menu (see figure below) for the user to select the directory and file name into which information about all the chromosome bands will be saved.
2.1.1.2.2 Dump BAC:
Save all of the BAC clone information currently in the database server into a file in ACeDB format so that the saved file can be read in by the 'AceDB' program.
Choosing this option brings up a file selection menu for the user to select the directory and the file name into which information about all YAC clones (with or without position values) will be saved.
2.1.1.2.3 Dump YAC:
Save all of the YAC clone information currently in the database server into a file in ACeDB format so that the saved file can be read in by the 'AceDB' program.
Choosing this option brings up a file selection menu for the user to select the directory and the file name into which information about all YAC clones (with or without position values) will be saved.
2.1.1.2.4 Dump STS:
Save all of the STS marker information currently in the database server into a file in ACeDB format so that the saved file can be read in by the 'AceDB' program.
It brings up a file selection menu for the user to select the drive and the file name into which information about all STS markers (with or without position values) will be saved.
2.1.1.2.5 Dump All Above
Save all data entries related to all above (Chrom Band, BAC, YAC and STS) currently in the database server into a file in ACeDB format so that the saved file can be read in by the 'AceDB' program.
It brings up a file selection menu for the user to select the drive and the file name into which all related data entries will be saved.
2.1.1.3 Empty Database
It simply erases all data entries currently existing in the SQL database server. When selected, it brings up a dialog window and asks whether or not the user intends to delete the whole database entries in the server. Make sure all data entries have been saved using above "Dump .ace File" menu option before you really intend to empty the database!
2.1.1.4 Print Map:
Output the contig map to either a color printer or a postscript file according to user selected parameters which are set in the map printing window (see figure below).
Selections for printing parameters include:
2.1.1.5 Exit Program:
Exits the program. A dialog box is brought up to confirm (see figure below). Click on "Yes" to exit or "No" to return to the program.
2.1.2 Edit Menu:
The "Edit" menu (see figure below) contains the following menu items:
2.1.2.1 Create BAC:
Create a BAC clone from scratch. A pop-up window is brought up for new data entry (see figure below).
After the data have been entered into the appropriate fields in the pop-up window, click on "SAVE" to store the data into the database, or "CLOSE" to close the window and cancel the creation.
When saving, if the name already exists in the BAC database, a pop-up window is brought up (see figure below). Click "Yes" to overwrite the existing BAC clone with same name, "No" to cancel the creation entirely. Note that if the left position value is larger than the right position value, the program will auto-correct this by switching the two values during saving.
2.1.2.2 Create YAC:
Create a YAC clone from scratch. A pop-up window is brought up for new data entry. After the data have been entered, click on "SAVE" to store the new data in to the database, or "CLOSE" to cancel.
When saving, If the name already exists in the YAC database, a pop-up window is brought up. Click "Yes" to overwrite the data, "No" to cancel the creation entirely.
2.1.2.3 Create STS:
Create an STS marker from scratch. A pop-up window is brought up for new data entry. After the data have been entered, click on "SAVE" to store the data into the database, or "CLOSE" to close cancel.
When saving, if the name already exists, a pop-up window is brought up. Click "Yes" to overwrite the data, "No" to cancel the creation entirely, and "CLOSE" to not overwrite, but keep the STS marker on the screen.
2.1.3 Tools Menu:
The "Tools" menu (see figure below) contains the following menu items:
2.1.3.1 Change Color:
There are 2 ways to change an object's color: a panel of 27 predefined colors, and a color pallete for fine control:
2.1.3.1.1 Use Panel:
First, using a single mouse click, select the object whose color is to be changed. Then choose this menu item to open the color selection window (see figure below) and select the desired color by clicking the desired color rectangle and pressing the "Ok" button.
2.1.3.1.2 Use Pallete:
First, using a single mouse click, select the object whose color is to be changed. Then choose this menu item to open the color selection window (see figure below) and select the desired color by clicking the desire color from the color pallete and sliding the "value" slider or by entering "Red", "Green" and "Blue" values (or using their sliders). Press the "Ok" button to use the selected color or press "Cancel" to cancel this action.
2.1.3.2 Find:
To search the database for an object (a chromosome band, an STS site, or a BAC clone), choose this menu item to open a query box window (see figure below). Type the object's catalog number (name, "A-112B5" in this example) into the query box, then press the "Find" button. Use the "Clear" button to clear the text in the query box or use "Close" to cancel the search.
If the object being queried is not found in the database, a dialog window appears, displaying "Query Result: Not Found". The dialog can be dismissed by clicking "Yes".
If the object being queried is found in database, a pop-up window containing information about this object (chromosome band, or STS site, or clone) is brought up. For objects other than chromosome bands, the pop-up allows the user to modify information about the object.
If the found BAC clone has left and right position values (i.e. it is a "visible" BAC clone), BAC clone "A-451C8" for example, the screen is centered on it; the BAC clone is highlighted in red; its name is displayed in the active object name box; and its position values are displayed in the coordinate box, through which its position values can by modified by user (see figure below).
Meanwhile, a pop-up window containing information about this BAC clone is opened (see figure below). Through this pop-up window, the user may modify or delete the BAC clone.
If the found STS site has a position value (i.e. it is a "visible" STS site), "s5F1" for example, the screen is centered on it; the STS site is highlighted in red; its name is displayed in the active object name box; its position value is displayed in one coordinate box (left side), through which its position value can by modified by user (see figure below).
Meanwhile, a pop-up window containing the information about this STS site is opened (see figure below). Through this pop-up window, user may modify or delete this STS site.
If the found object does not have position value(s) (i.e. it is an "invisible" object), a pop-up window containing information about this object appears without changing the main screen. See figure below of a BAC clone pop-up window after querying an "invisible" BAC clone that does not have left or right position values ("A-430F1").
Also see figure below of a STS site pop-up window after querying a "invisible" STS site that does not have position value ("WI-4098")
2.1.3.3 Move Multiple Objects:
Use this option to move a number of STS markers and/or BAC clones, YAC clones together along the chromosome. When selected, it opens up a pop-up window (see below) for inputs about the distance offset and object names.
2.1.4 Window Menu:
The "Window" menu (see figure below) contains the following menu items:
2.1.4.1 Zoom In:
Zoom in on the display by a factor of 2. The center of focus is not changed unless necessary to prevent the zoomed range from going beyond the ends of the chromosome. The locator, the zoomed-chromosome, STS marker, and clone displays change accordingly (see figure below).
2.1.4.2 Zoom Out:
Zoom out on the display by a factor of 2. The center of focus is not changed unless necessary to prevent the zoomed range from going beyond the ends of the chromosome. The locator, the zoomed-chromosome, STS marker, and clone displays change accordingly (see figure below).
2.1.5 Help Menu:
The "Help" menu (see figure below) contains the following menu items:
2.1.5.1 About AceDraw
Information about the AceDraw programming team.
2.2 Full-View Chromosome Display
The top portion of the screen contains a whole view graphical representation of the chromosome being mapped, arranged horizontally. This displays the banding of the entire chromosome.
This full-view ruler gives the coordinates in AceDB units corresponding to full-view chromosome above it.
2.4 Locator
The locator bar is below the full-view chromosome and ruler display.
By clicking on and dragging the endpoints of the slider, the locator can be resized. By clicking on the middle region of the locator and dragging it to the left or to the right, the locator can be moved. Following the resizing or moving of locator, the zoomed-view chromosome, zoomed-view ruler, STS markers and BAC clone displays, which are underneath the locator, are changed accordingly.
2.5 Zoomed-View Chromosome Display
Immediately below the locator is the zoomed representation of the full-view chromosome, scaled to the zoomed region of the chromosome. This shows only the section that is currently zoomed, and the labels of the bands that show up there. The chromosome is zoomed whenever the locator is repositioned, either with the mouse or using the coordinate boxes (see below).
A single left click on a band results in the the band being highlighted in red. Double clicking on a band displays a pop-up window containing information about the band (see figure below).
This information cannot be modified. Click on "CLOSE" to close the pop-up window.
This zoomed representation of the full-view ruler is scaled to the zoomed region of the whole-view ruler. It is displayed in ACeDB units and corresponds to the zoomed-view chromosome.
2.7 STS Marker Sites
Below the zoomed-view ruler are the STS marker sites, represented by a small triangle pointing upwards at the zoomed ruler, and the catalog number (name) of the markers. The size of these triangles may be changed according to zoom factor (The bigger the zoom factor, the bigger the size).
By left-clicking on the marker, the marker's name is displayed in the active object name box and its position value is displayed in and can be altered through the left coordinate boxes. Note that the right coordinate box becomes empty and uneditable when an STS marker is clicked since STS markers has only one position value. By left-clicking on the marker and dragging it, the marker's position is altered on the screen. When it is moved outside of its positive BAC region, a confirm window appears (see figure below).
Click on "Yes" to save the changes. Clicking on "No" cancels the move and brings the marker back to its original position before dragging occurred.
Double-click on the marker to bring up a pop-up window through which user may modify or delete the STS marker (see figure below). Please refer to Section 3.3.2 for more details.
The remaining portion of the window is taken up by the display of the BAC clones as horizontal bars in different rows. The catalog numbers (names) of BAC clones are displayed in the middle of clones but only when the bars are big enough (depending on current zoom factor). If either end of the clone is sequenced, it shows up in "bright" color at that end where they were sequenced. If the clone is fully sequenced, it appears as whole in "bright" color.
When a BAC clone is selected by single left-clicking, it is highlighted in red; its name is displayed in active object name box (see below); and its left and right position values are displayed in and can be altered through the left and right coordinate boxes.
By clicking on and dragging the endpoints of a clone, the clone can be resized. Note that this can be done only if the clone clicked is not fully sequenced. For fully sequenced clones, resizing by dragging is prevented.
By clicking on and dragging the middle portion of a clone, the clone can be moved to different position.
The left and/or right position values are changed during above resizing or moving operations. When the clone gets moved/resized out of its positive STS markers region, a confirm window appears (see figure below). Click on "Yes" to save the changes. Clicking on "No" undoes the move/resize and brings the clone back to its original position before dragging occurred.
When a clone is moved/resized so that other clones in the same row get hidden behind the moving clone, they automatically jump up or down to some rows that are empty as soon as they collide with the moving clone.
By double-clicking on a clone, a pop-up window containing the information about this clone is brought up and the user can also modify the clone through the pop-up window (see figure below): click on "SAVE" to save changes made to this clone into database, on "DELETE" to delete this clone from database, on "CLOSE" to abort any changes made. Please refer to Section 3.3.3 for more details.
If the left position of a clone is greater than its right position (by changing the values in the pop-up window or in the coordinate boxes), the values are simply flipped over.
The bottom of the main window contains some useful tools as following:
2.9.1 Active Object Name Box:
It displays the name (or catalog number) of currently selected object.
2.9.2 Left and Right Coordinate Boxes:
The text fields in the coordinate boxes display the position values (in AceDB units) for the object currently selected by user. Click on the up and down arrows in the right side of the left or right coordinate box will change the text values of the coordinate boxes (depending what object is currently selected, see below) by a certain incremental value (300 AceDB unit).
If the selected object is locator, the locator's left and right end position values can be changed to change the zoom factor and the portion of the zoomed chromosome being displayed. This would change the display of the locator (same effect as resizing locator by mouse). The display of STS markers and BAC Clones currently on screen is changed accordingly as well.
If the selected object is an STS marker, its position value is displayed in the left coordinate box (the right coordinate box is temporarily deactivated and becomes blank). Changes in the left coordinate box would have the same effect as moving the STS marker by mouse (for example, a confirm window is brought up is the changed STS marker's position is outside positive BAC clone region).
If a BAC clone is the selected object, its left and right position values are displayed in the left and right coordinate boxes respectively. Changes in either of the coordinate boxes would have the same effect as resizing the clone by mouse (for example, a confirm window is brought up is the changed clone's position is outside positive STS marker region). If user changes the coordinate boxes such that further changes would make the value in the left coordinate box bigger than value in the right coordinate box, the clone's position value will not get changed.
3.1 Basics
To start the program, make sure the acedraw executable file is in the current directory or in the "path" variable and the mySQL database server is up running and able to receive client queries, then issue the following command at the command prompt:
acedraw -i[host_name or IP#] -u[username] -p[password] -d[database_name]
You can use environment variables instead of command line arguments to tell AceDraw how to contact the database. If you use csh or a csh-derived shell such as tcsh, put the following lines into your .cshrc file (substituting the correct values for your site's database):
setenv ACEDRAW_DBHOST "IP_ADDRESS_OF_YOUR_mySQL_SERVER_HERE"
setenv ACEDRAW_DBUSER "genome"
setenv ACEDRAW_DBPASSWORD "genome"
setenv ACEDRAW_DBNAME "chrom16"
If you use a Bourne-style shell (such as sh, ksh, or zsh), put the following lines into your .profile (or equivalent) file, again substituting the correct values for your site:
ACEDRAW_DBHOST="IP_ADDRESS_OF_YOUR_mySQL_SERVER_HERE" export ACEDRAW_DBHOST
ACEDRAW_DBUSER="genome" export ACEDRAW_DBUSER
ACEDRAW_DBPASSWORD="genome" export ACEDRAW_DBPASSWORD
ACEDRAW_DBNAME="chrom16" export ACEDRAW_DBNAME
Now just issue 'acedraw' and the program should start. You can use any combination of environment variables and command line arguments. Note that command line arguments override environment variables.
To select an object (for example, locator, chromosome band, STS marker, BAC clone), simply left click on the object. The selected object will get highlighted in red.
For chromosome bands, STS markers, and BAC clones, double click on the object to display all relevant information about the object through a pop-up window.
3.2 Creating Objects
To create a STS marker, BAC clone, or YAC clone, go to the Edit menu and select one of the "Create XXX" items to bring up an appropriate pop-up window. Enter the new data to the data fields in the pop-up window that appears, and press "SAVE" to save the new data into the database. The new object will also be "visible" if its position value(s) is assigned and appear on the screen if it is in current zoom region. If the created object has a name that already exists in the database, an "overwrite warning" dialog window is opened and asks user to confirm the action. Press "Yes" to overwrite the existing object or press "No" to cancel the creation. Please refer to Section 2.1.2.1 for more details.
3.3.1 Modifying chromosome Band:
Double click on the band on the zoomed-view chromosome display, or query the name of the chromosome band to bring up a pop-up window containing information on the chromosome band to be modified. The chromosome band pop-up window consists of the following fields: Name, Left Position, Right Position, Type, and Appearance. After making the appropriate changes, click "SAVE" to store the changes into the database, and "CLOSE" to close the window. (Note: in current version of "acedraw" program, chromosome band is supposed to be read only. Therefore, only "CLOSE" button is available). Please refer to Section 2.5 for more details.
3.3.2 Modifying STS marker:
Double click on the triangle representing the STS marker to be modified, or use the query box to query into the catalog number of the STS marker, to bring up a pop-up window. The pop-up window for the STS markers consists of the following fields: Name, GDB_id, GB_id, Remark, oligo_1, oligo_2, Length, Position, Originator, and Location. After making the appropriate changes (NOTE: no changes should be made to the name. If the name needs to be changed, the "Create STS" button should be used) , click on "SAVE" to store the changes into the database, and click on "CLOSE" to cancel any of the changes the user may have made and to close the window. Single left-clicking on a marker and it will be highlighted. The left coordinate box now displays the position of the marker with respect to the chromosome. The position of the marker can be changed on the screen by changing the value in the left coordinate box by clicking on the arrows in the left coordinate box. Please refer to Section 2.1.2.3 for more details.
Single left-clicking on a marker and dragging the mouse moves the marker to a new position on the screen. If an STS marker on the screen is moved by any of the above methods within its positive BAC range, the new position of the marker will be saved into the database. On the other hand, if the marker is moved outside of its positive BAC range and "Yes" is clicked in the confirm window, the new position will be saved to the database. Otherwise, no changes are saved and the marker returns to its original position on the screen. Please refer to Section 2.7 for more details.
3.3.3 Modifying BAC clone:
Double click on the clone or query the name of the clone to bring up a pop-up window containing information on the clone. The BAC clone pop-up window consists of the following fields: Name, Remark, Left Position, Right Position, Left End, Right End, Sequenced by, In situ, Sequence, Sequence Length, and Gel Length. After making the appropriate changes, click "SAVE" to store the changes into the database, or "CLOSE" to cancel the changes and to close the window.
Single left-clicking on a clone and it gets highlighted. The left/right coordinate boxes now display the left/right positions of the clone with respect to the chromosome. The left/right positions of the clone can be changed on the screen by changing the values in the left/right coordinate boxes by clicking on the arrows in the left/right coordinate boxes.
Single left-clicking in the middle of a clone and dragging the mouse moves the clone to a new position on the screen. Single left-clicking on the ends of the clone and dragging the mouse resizes the clone at the end that was clicked only if the clone is not fully sequenced.
If the clone on the screen is moved by any of the above methods within its positive STS marker range, the new position of the marker will be saved into the database. On the other hand, if the marker is moved outside of its positive STS range and "Yes" is clicked in the confirm window, the new position will be saved to the database. Otherwise, no changes are saved and the clone returns to its original position on the screen.
Note that if the left position of a clone is greater than its right position after change, the values are simply flipped over during saving. Please refer to Section 2.8 for more details.
3.4 Deleting Objects
If the user presses the "DELETE" button in the pop-up window that appears when a STS marker/BAC clone is double clicked or STS marker/BAC clone is queried and the object exists, the object is deleted from the screen and the database.
3.5 Saving into database files
Click on one of the "Dump" buttons in the Tool bar at the top of the screen to save all of the relevant information into a file on a local drive in ACeDB format. The mapping data in these files can be read back into ACeDB program. The figure below is the screen shot of AceDB after parsing these files saved from "AceDraw".
See Section 2.1.1 for more details about saving into AceDB format database files.
To change the color of a object of interest, select that object by a single mouse click, then go to "Tools" menu and choose "Change Color" (select either "Use Panel" or "Use Pallete"). Select the desired color and press "Ok". Please refer to Section 2.1.3.1 for more details.
To print the contig map to a color printer or to a postscript file, go to "File" menu to select "Print Map" to bring up the map printing parameter selection window. Enter appropriate values or select appropriate options and press "Ok". Please refer to Section 2.1.1.4 for more details.
The user can search for a particular chromosome band, STS marker, or BAC clone by its name (catalog number). Go to "Tools" menu to select "Find" to bring up a query box window, then type in the name of the object to be searched in the query box and press "Find". If the queried object has position value(s), screen is centered on it, the object being highlighted in red, its name being displayed in active object name box, and its position value(s) displayed in coordinate box(es). If that entry does not have a position value (i.e. "invisible"), the information is displayed in a pop-up window but the screen is unchanged. Please refer to Section 2.1.3.2 for more details.
3.9 "Invisible" STS markers and Clones
"Invisible" STS markers, as well as clones, which do not possess positions, can also be searched. They can also be modified and deleted afterwards by querying their names. When an "invisible" STS marker or clone is found, a pop-up window is opened that displays all their attributes. Click on "SAVE" to save it into database after modifying the appropriate data fields through the pop-up window. Click on "CLOSE" to close the pop-up window and no changes are saved into database. Please refer to Section 2.1.3.2 for some more details.
Note that when object is deleted, the program just erase the object's position value(s) without deleting the object's name and other data fields (according to Dr. Kim's request). Therefore, deleted objects should still be searchable through the query box window.
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