quodlibet editor guide 1 - datapunk | · pdf...
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EDITOR GUIDE, VERSION 1.4
HTTP://WWW.DATAPUNK/QUODLIBET/
COPYRIGHT 2011-‐2012 PETER D'ADAMO AND HOOP-‐A-‐JOOP, LLC
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WELCOME TO QUODLIBET EDITOR..................................................................................................4
BECOMING A QUODLIBET EDITOR....................................................................................................5
FIRST THINGS FIRST ......................................................................................................................5
HOW TO APPLY.................................................................................................................................5
ACCESSING THE EDITOR........................................................................................................................6
EDITOR LEVELS ................................................................................................................................6
THE QUODLIBET EDITING ENVIRONMENT ..................................................................................7
LOG OUT...............................................................................................................................................7
ENTER EDIT MODE .........................................................................................................................8
VIEW AS USER ...................................................................................................................................8
EDIT MAP DETAILS .........................................................................................................................8
ADD NEW NODE ...............................................................................................................................9
ADD NEW EDGE................................................................................................................................9
ADD CONCEPT NODE .....................................................................................................................9
A QUICK EDITING TUTORIAL............................................................................................................ 10
GETTING STARTED ...................................................................................................................... 10
YOUR FIRST EDIT: ADDING NEW NODE............................................................................. 11
ADD A NEW EDGE......................................................................................................................... 14
THE ADD NEW EDGE MENU..................................................................................................... 16
ADVANCED EDITING TECHNIQUES................................................................................................ 20
MAP-‐WIDE EDITS ................................................................................................................................... 21
EDITING EXISTING NODES AND EDGES....................................................................................... 22
CREATING COMPLEX NODES ............................................................................................................ 23
ADDING CONSTITUENTS TO A NODE .................................................................................. 23
NODE CLUSTERS ........................................................................................................................... 25
RANKING NODES........................................................................................................................... 26
LINKS, SHAPES, COLORS AND STYLES ................................................................................ 27
PORT NODES ................................................................................................................................... 28
JUNCTION NODES ................................................................................................................................... 30
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CONCEPT NODES .................................................................................................................................... 31
WORKING WITH CONCEPT NODES IN YOUR CANVAS................................................. 31
INSERT CONCEPT NODE INTO MAP..................................................................................... 32
EDITING CONCEPT NODE FEATURES IN YOUR MAP.................................................... 35
EDITING THE CONCEPT NODE ITSELF ............................................................................... 35
ADDING A NEW CONCEPT NODE........................................................................................... 36
ASSOCIATING NATUROPATHIC AGENTS..................................................................................... 39
ASSOCIATING A NATUROPATHIC AGENT.......................................................................... 40
HOW TO DO IT................................................................................................................................ 41
ADDING NEW AGENTS TO THE DATABASE...................................................................... 47
PARTIAL MATCHES...................................................................................................................... 49
PROFILING NATUROPATHIC AGENTS........................................................................................... 50
ADDING TO AN EXISTING AGENT PROFILE OR CREATING A NEW ONE............. 50
TINY MCE.......................................................................................................................................... 53
THE QUODLIBET COMMUNITY ........................................................................................................ 55
THE QUODLIBET FORUMS........................................................................................................ 55
ADDENDUM: THE KEGG MAPS PROJECT ..................................................................................... 57
COPYING KEGG MAP DATA INTO QUODLIBET................................................................ 57
FINAL THOUGHTS .................................................................................................................................. 60
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WELCOME TO QUODLIBET EDITOR
A quodlibet is a piece of music combining several different melodies, usually popular
tunes, in counterpoint and often a light-hearted, humorous manner. The term is Latin,
meaning "whatever" or literally, "what pleases."
QUODLIBET is a suite of network creation, editing and querying software written by
Peter D'Adamo. QUODLIBET is a software application that displays biochemical
pathway data in a way that is interactive and information intensive. QUODLIBET is
one of several informatics solutions that run under the DATAPUNK operating
environment. DATAPUNK is a unique web-‐based suite of programs that provide an
assortment of informatics services.
This guide is details how to:
• Create, edit and update uniquely 'thinking' metabolic and pathway maps
• Tag and associate naturopathic agents with metabolic entities (genes, enzymes,
compounds, etc) so that these association can be used to enrich maps.
It assumes that you have:
• Read the QUODLIBET USERS GUIDE
• Have some familiarity with the interface as a user
• Have good basic computer skills
• Have a SVG graphics capable browser and a decent Internet connection
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BECOMING A QUODLIBET EDITOR
Anyone can edit in QUODLIBET. You don't need a PhD in genetics or an ND degree in
naturopathic medicine: An abiding interest in human biology, a passion for
exactness, and some basic user skills will easily suffice. Many community-‐based
online projects, including FOLD-‐IT (a program the allows non-‐scientists to guess
how certain proteins fold) have had surprisingly large amounts of highly useable
work done by non-‐scientists. Essentially, if you have updated a FaceBook page or
purchased something from eBay you are probably qualified to become an editor in
QUODLIBET.
FIRST THINGS FIRST
Before you consider becoming an editor, make sure that you have become a power-‐
user. Playing around in the Sandbox, getting a good idea of the interface and reading
the Quodlibet User Guide (accessed by clicking the icon with the large letter 'i' on the
main page or from the main canvas when not in edit mode) are essential to become
a good user, and good users become great editors. Take your time with this guide.
QUODLIBET editing actions may seem daunting at first, but over time they should
become intuitive 'muscle memory'. You'll just need to get familiar with things and
there are lots of ways to practice experiment and take risks without breaking
anything
HOW TO APPLY
To apply for a QUODLIBET editing account please send an email to Peter D'Adamo
([email protected]) with the words QUODLIBET EDITOR in the subject line.
Include any special interests or skills and an approximate estimate of the number of
total hours per week you envision being able to devote to the project. If approved,
you will be sent a return email with a special user name and password you can then
use to access the special editor functions.
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ACCESSING THE EDITOR
To begin editing you must first log in. Do this by first opening up any clicking the key
icon from any open map or from the main QUODLIBET page.
This action will open up a new pop-‐up window with entry fields for your user name
and password. Both are case-‐specific. Enter this information and press the button. If
accepted the screen will provide a link that updates the main window to your new
editor status.
QUODLIBET work environment: A pop-‐up and main canvas.
EDITOR LEVELS
Depending on your experience, you may be approved to work on one metabolic map
by yourself, or as part of a workgroup, or as a workgroup leader, or even be given
super-‐admin right, where you can go in and tweak almost anything. Most beginning
editors are assigned to one ongoing project, usually under the direction and
supervision of a more experienced editor or curator.
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THE QUODLIBET EDITING ENVIRONMENT
The editor is designed to function the same way as the user environment, i.e. you
use a small popup window to control the larger canvas. Just like the normal user
environment, you can access specific nodes and edges for editing by clicking directly
on them. An addition set of features in the upper right navigation area provides for
several addition functions. Hovering your mouse over these features provides a
short descriptive tag.
From left to right, these additional options include:
LOG OUT
This icon link ('man leaving') logs you out by erasing the cookie from your browser
than identifies you as an editor. QUODLIBET automatically logs you out when you
turn off your computer or close your browser, but you may want to log out if you are
on a shared system, etc.
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ENTER EDIT MODE
This icon link ('wrench and hammer') reloads the screen and displays the map in
edit mode and activates the editing toolset.
VIEW AS USER
Visible, when in edit mode this icon link ('eyeball') reloads the screen and displays
the map as if you were an ordinary regular user. Since the maps are draw
dynamically and the editor canvas contains extra tags and links a map might display
a bit differently (although usually only very slightly) in the editor canvas than in the
regular user environment.
EDIT MAP DETAILS
This icon link ('globe with a pen') opens up a popup window that allows you to edit
the title of the map and the descriptive paragraph. These display in the upper info
area.
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ADD NEW NODE
This icon link ('circle') opens up a popup window that allows you to add a new node
to the map.
ADD NEW EDGE
This icon link ('arrow') opens up a popup window that allows you to add a new edge
to the map.
ADD CONCEPT NODE
This icon link ('arrow') opens up a popup window that allows you to a special node
that contains a non-‐calculating 'concept' (like 'Increased Glycolysis') rather than a
gene or compound. These types of nodes are discussed in detail later on in the guide.
All these functions are discussed in greater detail on the following pages.
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A QUICK EDITING TUTORIAL
The best way to learn how to use the QUODLIBET editor is to jump in and get your
feet wet. To accomplish this we will edit a map called 'Sandbox'. Sandbox is an
unbreakable playground to hone your QUODLIBET skills. After about an hour of use
the Sandbox resets back to its original state, so you don't have to worry about
removing what you've added.
GETTING STARTED
From the main QUODLIBET page, click on the login (key) icon to open up the log-‐in
pop-‐up window. You can log in with the username guest and the password quodlibet
to gain access to the editor and allow you to play in the Sandbox. Click on the load
map icon (the file folder) and select the Sandbox map. Click on the enter edit mode
icon (the wrench and hammer) to enter edit mode.
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YOUR FIRST EDIT: ADDING NEW NODE
The simplest edit you can perform in QUODLIBET is to add new nodes or edges. So
let's begin by adding a new node and then connecting a new edge to it. Click the 'Add
a New Node' link (the circle icon) in the upper right navigation menu.
The 'Add New Node' icon link
This will open up or update the popup window with a form to fill out describing our
new node.
Adding New Node pop-‐up window.
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Although the form has lots of input fields, don't be intimidated. Most of these are
optional and will be discussed later in the 'Advanced Editing' section. For now, we
will just add a simple node. Looking at the form we should note a few things:
• The form is a bit longer than the popup window, so use the scroll bar to move up
and down to see all the form contents. The 'Submit Network Edit' button is at
the bottom of the form so remember to scroll down when it comes time to
submit the form.
OK, so let's add the node. Give the node a suitable name, perhaps a hometown or
favorite city. We will name our node 'Seattle'. However notice what happens as you
begin to type the first few letters of 'Seattle':
QUODLIBET auto-‐complete.
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Through the magic of computer science QUODLIBET suggests possible entries for
you to consider. However QUODLIBET auto-‐complete suggestions derive from a
database of 32,000 approved gene-‐protein names so it cannot suggest things like
city names.
If we did nothing else but hit the Submit Network Edit button at this point we will
have created the most basic simple node ('Seattle') with the most basic format (a
light-‐blue circle). However, we want to distinguish ourselves a bit, so we will instead
tell QUODLIBET that our new node will be a diamond shaped and tan colored. To do
those just select diamond from the Shape pull down field and tan from the Base
Color pull-‐down field. Now scroll down and hit the 'Submit Network Edit' button.
The editing pop-‐up window should now look something like this:
If you click on the link that updates the main window you should now see your new
node.
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Your first node.
Success! Congratulations, you are now well on the way to a stellar career in
QUOLIBET editing! However, one thing should be quite apparent: our new Seattle
node is not connected to any other node in the network. This will not do! So let's
make the connection.
ADD A NEW EDGE
Connections between nodes are called edges, so from our upper right navigation
menu, we will now click on the 'Add New Edge' link, which looks like an arrow.
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The 'Add New Edge' icon link
This updates the pop-‐up window with the form needed to add a new edge
connection.
The Add New Edge pop-‐up form.
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THE ADD NEW EDGE MENU
Edges are somewhat simpler than nodes, and because of this the Edge menu has less
options than the one we used to create a new node. Because edges are so much
simpler, we’ll discuss the entire menu here.
Looking at the form we should note a few things:
• A few fields are already populated. These automatically assign the new node a
unique ID number and the code letter 'E' for edge. These needn't be changed.
From Node and To Node
Unlike a node that requires only a simple name, edges require information about
where they need to connect things. If we consider an edge to be a 'road' or
'highway', we obviously will need to tell it which two 'towns' to connect. Providing a
From Node and a To Node does this. In addition to specifying which nodes the edge
connects, the From Node and To Node fields tell QUODLIBET what direction the edge
is to assume; in other words, which direction the arrow of the edge points. Since
Seattle is close to Vancouver, lets connect our new Seattle node to the Vancouver
node. In this case we'll make Seattle the From Node and Vancouver the To Node.
Notice what happens when you begin to enter 'Seattle' in the From Node field.
QUODLIBET suggests this for you. This will also occur when you begin to enter
'Vancouver' into the To Node field. This 'auto-‐complete' helps eliminate spelling or
typing errors, which is a big thing with computers, who have hang-‐ups about this
type of thing. If possible always accept an auto-‐complete answer, since that is the
name QUODLIBET is expecting.
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Although you can successfully create a new edge by simply setting a From Node and
To Node, there are optional effects, links and other jazzy things you can add to the
edge.
Label
A label is simply a name tag that displays next to the edge. A common edge label in
biochemistry is to mark an edge with the tags '+p' or '-‐p' to denote whether a
reaction (symbolized by the edge) resulted in the addition or subtraction of a
phosphate group. We on the other hand will be considering our new edge to be a
road between Seattle and Vancouver, which incidentally, is Interstate 5. So let's label
our new edge 'I-‐5'.
Web Link
Adding a web address here converts our label to an internet hyperlink. Perhaps you
may want to add the Wikipedia entry for Interstate 5:
http://en.wikipedia.org/wiki/Interstate_5
Color
This pull-‐down menu allows you to specific a color for your edge: the choices are
blue (default), grey, brown and red.
Class
This pull-‐down menu allows you to specific a class or type for your edge: the choices
are Normal-‐directed (default), Inhibitory and Undirected. Normal-‐directed draws a
blue edge with a normal arrowhead pointing to the To Node. Inhibitory draws a
brown edge with the reverse arrowhead pointing to the To Node. Undirected edge
draws an edge without any arrowhead.
Border Style
Sets the style of the edge: options are Solid (default), dashed and dotted.
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We want a nice, simple edge so for now just leave everything as-‐is so after adding
the From and To Nodes, the 'I-‐5' label, and the link to the Wikipedia article on
Interstate 5, press the 'Submit Network Edit' button. The editing pop-‐up window
should now look something like this:
If you click on the link that updates the main window you should now see your new
node connected to your new edge:
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Since you are in the edit mode, the edge link to the Wikipedia article will not work
(it will instead take you to the edit pop-‐up for the edge). So to see what the 'real
world' version of your new edge looks and behaves like click on the 'View in Non-‐
edit Mode' link in the upper right navigation area.
The 'View In Non-‐Edit' link
You should now be able to click on the I-‐5 link and be instantly teleported to the
Wikipedia entry on Interstate 5.
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ADVANCED EDITING TECHNIQUES
Although simple nodes and edges can comprise much of what lies behind a complex
network, QUODLIBET has many optional features that can imbue a node, edge or the
entire graph with far greater significance and value. These are discussed in the
following section.
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MAP-‐WIDE EDITS
You can edit map-‐wide details by clicking the 'Edit Map Details' icon symbol (globe
and pen).
The 'Edit Map Details' icon.
This will open up the Edit Map Details pop-‐up.
In general it is not a wise idea to unilaterally change map titles and descriptions.
These are best done as a result of a consensus that results from discussions about
the particular map you are working on taking place on the QUOLIBET Editors Forum.
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EDITING EXISTING NODES AND EDGES
Clicking on the node or edge link for the particular node or edge you wish to edit
brings up the Editing Node/ Edge pop-‐up.
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CREATING COMPLEX NODES
ADDING CONSTITUENTS TO A NODE
If only every node in a biochemical network were simple! However this is more the
exception than the rule. Most genes and their protein derivatives have any number
of 'family members': intermediates, metabolites or variants. If you remember from
the QUODLIBET Users Guide clicking on the Disheveled (DVL) node showed that DVL
is actually a node comprised of three constituents, DVL1, DVL2 and DVL3. The visual
giveaway is that complex nodes are colored lilac, while simple nodes are light blue.
Let's edit the constituents for a node. In this case we will be adding a tag for a
constituent that is a synonym for the node name. This is a common task, because
many genes and proteins have had history of having multiple names. Adding
synonyms as constituents to a node helps QUODLIBET find any relevant information
about the node when a user clicks on it. Clicking on the node TACE will bring up the
Edit Node pop-‐up
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TACE (tumor necrosis factor-‐α-‐converting enzyme), a 70-‐kDa enzyme that belongs
to the ADAM protein family of disintegrins and metalloproteases, is also known as
ADAM metallopeptidase domain 17 (ADAM17). We are going to tell QUODLIBET
that in this map when looking for information on TACE, also look for any data for
ADAM17 as well. So, go over to the first box under Constituents and begin to type
ADAM17. You should notice that QUODLIBET autocomplete your answer. Always use
an autocomplete suggestion if it is correctly offered. This eliminates typographic
errors from things link space characters or invisible stuff that can compromise
QUODLIBETS search accuracy.
Press the Submit Network Edit button (remember to scroll down to see it) and click
the Update Main Window link to refresh the main window. You should now see the
TACE node colored an attractive lilac, signifying that it contains your new data.
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NODE CLUSTERS
Nodes can be clustered together to represent a type of grouping. This typically takes
the form of cell compartments or perhaps a process or particular organ. When
QUODLIBET draws a network map, nodes that share a cluster entry will be drawn
together inside of alight grey container. In the Sandbox map a number of nodes are
clustered together in the NUCLEUS cluster:
A group of nodes in a cluster (the grey box).
To assign a node to a cluster simpler enter a name for the cluster in the Cluster field
on the Add or Edit Node form. Nodes with the same named cluster will be clustered
together when the map is drawn.
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Prefacing the name of the cluster with the exclamation point character (i.e.
!mynode) can draw a special 'invisible cluster'. This can be used to group nodes
more tightly together, as the software automatically draws the maps and sometimes
this can result in confusing node placement. Clustering nodes together with the
invisible option can help control this.
RANKING NODES
As we've just learned, network maps are drawn dynamically in QUODLIBET. Indeed,
one of the guilty pleasures of editing and creating maps is the suspense of
anticipating just how QUODLIBET will draw the map after a few new nodes or
edges! However, it is sometimes desirable to help QUODLIBET along. One way to do
this is to set a Node Rank for nodes that you wish to have drawn on the same level.
Nodes that share the same rank will be drawn at the same level in the graph. Up to
five rank categories can be specified. Assigning node ranks can help the flow of the
graph: For example, grouping end products together with the same rank will tend to
keep them towards the bottom of the graph.
Selecting node rank in the node editor.
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LINKS, SHAPES, COLORS AND STYLES
Web Link
These fields allow you to add additional web links to the entry for this node. When a
user clicks on the node, in addition to information QUODLIBET provides out of its
own databases, the user will also be presented with these links as well.
Shape
This field provides a pull-‐down that allows you to select a shape for the node.
Options are: circle (default), triangle, box and diamond.
Base Color
This field provides a pull-‐down that allows you to select a base color for the node.
Options are: blue (default), white, tan and light green. This may be overwritten by
dynamically generated colors that result from any network analytics.
Border Style
This field provides a pull-‐down that allows you to select a border style for the node.
Options are: solid (default), dashed and dotted.
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PORT NODES
A Port Node is a complex node where several entities are represented as having a
certain level of functionality due to the complex formed by the individual
components of the port node. In molecular biology this might be used to represent a
co-‐activation complex formed by several transcription factors. Port nodes present as
a rectangle composed of boxes linked together.
A port node.
Creating a new port node or editing an existing node into a port node is simple.
Click on the PSEN-‐PSE2-‐NCSTN-‐APH port node in the Sandbox Map. This will open
up the Edit Node pop-‐up.
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The simplest way to create a port node is to tick the Port checkbox and enter up to
six name/tags (as with most text fields in QUODLIBET these will autocomplete).
Like any other node in QUODLIBET, port nodes must have a name. In this case we've
titled this port node 'Gamma Secretase Complex'. If you do not supply a name for
your port node, QUODLIBET will construct one out of the tags (i.e not naming this
port would have resulted in its being named 'PSEN-‐PSE2-‐NCSTN-‐APH.')
However, you may have noticed that there are tags in the Constituent fields that
differ from the tags that define the port node. This is because (just like any other
complex node) port nodes can contain data about derivatives and intermediaries. In
this case our APH label really defines a specific derivative APH1A (anterior pharynx-‐
defective 1), while PSEN describes PSENEN (presenilin enhancer 2) and PSE2
signifies PSEN1 (Presenilin-‐1) and PSEN2 (Presenilin-‐1). Having these constituents
defined enriches the ability of QUODLIBET to provide more specific detail when a
user clicks on this node.
You might be asking yourself at this point 'How in the world am I supposed to know
this stuff? The answer is, thankfully, that you don't have to know any of this at all.
For the foreseeable future most QUODLIBET editors will simply be transcribing
existing information from known molecular maps into the QUODLIBET system.
Sound redundant? Why copy a pathway map that already exists? The simple reason is
reasoning itself. Unlike inert hand drawn maps, such as those produced through KEGG
(Kyoto Encyclopedia of Genes and Genomics) once entered into QUODLIBET these
maps will be able to perform network calculations. Also, unlike other metabolic maps,
QUODLIBET maps are enriched with addition data about naturopathic agents capable
of influencing the expression and function of clusters and individual components of the
graph.
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JUNCTION NODES
Sometimes you need to denote an influence on a process (usually an edge).
Junction Nodes serve that purpose. These small nodes act as a junction (usually as
part of an edge) and allow you to plot the junction of influence(s) on the actions of
that edge.
A junction node between CycC node and DNA Survival Gene concept node allows for genes Bcl2/XL and
AIF to influence the process.
Creating a junction node is easy. Just tick the checkbox from the Add/Edit node pop-‐
up and give the junction node a single digit (0-‐9) label.
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CONCEPT NODES
So far we've been discussing the process of adding what might be called 'working
nodes' to your canvas. Working nodes are, to say the least, nodes that do some sort
of work: they might carry information about a naturopathic agent or contain other
constituent genes. These types of nodes are also involved in the calculations that
drive the Analytics pop-‐up.
Working nodes include:
• Normal simple nodes: These are the blue colored nodes
• Complex nodes: These hold other entities inside them and are the lilac colored
nodes
• Port Nodes: Square complexes of combinations
But most QUODLIBET canvases are not made up solely from working nodes. For
example, a pathway may terminate in a node that describes a process of some sort,
such as 'Increased insulin resistance' or 'Apoptosis.' We might consider these
Concept type nodes: Nodes that identify and teach about the context in which the
network functions and has meaning.
WORKING WITH CONCEPT NODES IN YOUR CANVAS
To insert concept nodes into a network, click the Add/Create Concept Node links
(triangle in box icon) from the menu at the upper right:
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The 'Insert a concept node' link.
This will open up the Concept Node pop-‐up. This pop-‐up features three mini-‐menus
that allow you to do these basic actions:
NOTE: As a guest editor you are only allowed to insert concept nodes into the Sandbox;
you cannot edit or create new concept nodes. When you receive full editing privileges,
you will gain these additional capabilities
INSERT CONCEPT NODE INTO MAP
This mini-‐menu put a new concept into your canvas. You can choose which concept
node to insert from pull-‐down that displays the collection of currently available
concept nodes. Unlike basic working nodes, where you are free (or even impelled)
to 'roll your own,' concept nodes are chosen and inserted from a toolkit of currently
available items. This is done to maintain conformity and continuity: The concept
node 'Apoptosis' will hyperlink to the same description popup in your map as it will
in any other map it appears in. Thus we only have to produce on very good entry on
Apoptosis versus create one anew for every different map that needs one.
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Insert concept node mini-‐menu
Inserting a concept node into a map is easy: try adding one into the Sandbox map.
From the pull-‐down, select one of the available concept nodes and press Submit. The
Concept node will appear as a white box with a grey border. From there you can link
concept nodes with edges just link any other node. Here we've inserted the concept
node Acyl-‐CoA and linked it to the Vancouver node.
A concept node in a network.
Now when a user clicks on the concept node Acyl-CoA they will be treated to the
following information pop-‐up:
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Concept node user information popup
There are other options available to you that allow you to enhance the function of
any concept node in your map. These embellishments will appear in your map only.
They do not change the actual entry for the concept node.
Labels Used in Map:
Filling in this field allows you to give the concept node a different label. For example,
if it would be more illustrative to name the Acyl-CoA concept node Oxidative
Degradation of Fatty Acids you can do that. However when the user clicks on the
node, they will still be taken to the entry for Acyl-CoA. If you don't enter a new value
in this field the node will be labeled with the base name of the concept node.
Cluster:
Just like any other node, concept nodes can be included in clusters.
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Rank:
Concept nodes can be ranked just like any other type node. Ranking nodes with
similar numbers results in those nodes being drawn at the same level.
EDITING CONCEPT NODE FEATURES IN YOUR MAP
This menu will also appear as an editing any time that you click on a concept node
from the canvas while in edit mode.
EDITING THE CONCEPT NODE ITSELF
The second mini-‐menu allows you to load one of the currently existing concept
nodes and edit its features. Unlike the earlier menus, this controls the permanent
features of the concept node: its permanent title, description, web links, etc. Select a
concept node and click the Edit Concept Node button. The pop-‐up will return with
the entry fields populated with the data about that node. Since the interface is
basically the same as the Add New Concept Node mini-‐menu that follows, we'll
discuss editing a concept node in the next section.
Editing Concept Node mini-‐menu
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ADDING A NEW CONCEPT NODE
Adding a new concept node would be necessary if your map requires a descriptive
node and there is no currently available concept node already created that would
suffice. For example, perhaps you map needed a node for Nerve Depolarization. We
could create a simple node, label it Nerve Depolarization and move on, but that is
somewhat limited. The new working node would be 'dumb' (i.e. unless we added
extra information about the node, when the user clicked on it, they would not be
given any additional information. So why not just add some information? Well, for
starters, that information would only be available in the map for which it was
created. Much better that your hard work should be used throughout the program,
not just on one map! Also, by only having one standardized entry and a consistent
identity, concept nodes themselves can 'think' as part of the network, when it comes
to analytics. Also one single entry insures that that entry be as good as it can be,
since anyone can improve it over time.
The Add New Concept Node mini-‐menu with Tiny MCE Editor.
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Adding a new concept node is simple and like most things in QUODLIBET, fairly
straightforward. At the top is a text filed for the name/title of the new field. Next is a
pull-‐down that allows you to associate your new concept node with an existing
external map. For example, you may need a new concept node for you map that
leads to the autophagy process. You could create a concept node called ‘Autophagy’
and from this pull down select the Autophagy map. Now QUODLIBET knows that the
concept node Autophagy links to an external map. When doing analytics
QUODLIBET can 'link' to the external map via this node and include it into its
network calculations.
Associating a new concept node with an existing external map.
The next section of the Add New Concept Node mini-‐menu allows you to add
descriptive text to the new concept node's node database. With an interface that
looks like a tiny word processor, you can add any sort of text, images, etc. This will
display as the information pop-‐up when a user clicks on this node when embedded
in any maps. There are many useful features to the editor; they are discussed on
page 48 in the next section.
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Text input field for entering descriptive text.
Finally, you can include up to four hyperlinks in your concept node entry. These will
be listed at the bottom of the entry. For each link you must include a title and a URL
(web address).
Add Web Links fields
Clicking the Add Concept Node button submits the form and saves your new entry.
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ASSOCIATING NATUROPATHIC AGENTS
One of the more powerful aspects of QUODLIBET is its ability to highlight
naturopathic procedures and agents that have been shown to exert an influence on
the expression or function of elements in a molecular network. This will have a
major influence on the future practice of Generative Medicine, since complex
patterns of relationships between naturopathic agents and procedures (traditional
as well as biomedical) can be superimposed over the network analysis of complex
molecular graphs so as to allow clinicians to derive extraordinarily high quality
suggestions about specific approaches that may more closely approximate the
holism of the Vis Medicatrix Naturae.
Nodes with associated naturopathic agents are identified with a Natural Products
Flag (NP Flag), a small dark green hexagon node containing a number that is
connected to the relevant node.
Nodes DVL and TACE with NP Flags showing that natural products associated with this node.
Clicking on an NP Flag from the User screen opens a pop-‐up with information on the
natural products associated with the control of this node.
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Naturopathic agent informatics popup
ASSOCIATING A NATUROPATHIC AGENT
Once a natural product has been linked to a gene or protein, this fact is available
throughout the program, not just the map you may be editing.
First and foremost we must realize that this process is a combination of sleuth
artistry and investigative science, hence there is no ‘right’ or ‘better way to do this.
QUODLIBET requires that a PubMed ID number accompany any link to a natural
product (the number that accompanies any abstract retrieved from PubMed.
How do we find a reference to a PubMed study to add to QUOLIBET? One simple
way to do it is to search PubMed (either directly or through the DataPunk search
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function) for research on that gene that may have included any natural products.
You probably do something like this frequently enough already.
HOW TO DO IT
While in editor mode, click on the Naturopathic Agents link (the mortar and pestle
icon)
The Naturopathic Agents Icon.
This will open up a popup with the Naturopathic Dashboard (described in the User
Guide). Because you are logged in you will see an additional option not visible to
visitors or when you are logged out: The Edit Database icon. Click it.
The Edit Database Icon
This will open up a new main window tab and take you to the Datapunk Search Box
Page. This is a new main window so check your browser tabs to see where it is.
Tagging natural products works from a DataPunk Search Box, which is the same as
the search function on the DataPunk Main Page (www.datapunk.net.) In fact, if you
are logged in and using DataPunk as you main PubMed browser, you will always be
able to tag naturopathics at any time. We'll be using the DataPunk PubMed search
box to surf PubMed for articles.
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The DataPunk PubMed search box page.
We will be looking for links between berberine (an alkaloid from Hydrastis
canadensis and Berberis vulgaris) and gene protein expression. Enering 'berberin' in
the search filed and pressing the Search DataPunk button brings up a search results
page. We scroll through the results until we see a potentially interesting article,
then click on its title.
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Datapunk search results page.
We settle on an article that appears promising: 'Berberine-‐induced AMPK activation
inhibits the metastatic potential of melanoma cells via reduction of ERK activity and
COX-‐2 protein expression.' Clicking on the title of the article brings up the abstract
page for the article.
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Datapunk article abstract page.
The abstract page looks very much like the standard PubMed page, though perhaps
with a bit more restful design!
Scrolling down, past the abstract paragraph, we can see a large gry box with lots of
blank entry boxes. This is where we will be working to link this article to our
collection of natural product data. By the way, this form is only available to
registered editors: If the form is not being displayed, it is because you have not logged
in.
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Datapunk natural product tagging form at the bottom of the abstract page.
Like other text fields in QUODLIBET, entering a term in the Naturopathic Agent area
of the form triggers QUODLIBET to try and autocomplete your entry. QUODLIBET
has an internal database of over 5000 procedures, herbs and nutrients and 30,000
genes, glycans and other compounds that it will use to try and autocomplete your
entry.
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The article mentions two gene/compounds linked to berberine: COX2 and AMPK.
These we enter in the fields under Entities (Genes, Compounds, Enzymes, etc.) It
doesn't matter which goes where. QUODLIBET will try to autocomplete your entries
for you, if it finds a suitable guess, but if it doesn't don't worry, it likes to learn new
things as well.
In the Naturopathic Agents we begin to type berberine and QUODLIBET knows the
term and autocomplete it for us. If there were more agents discussed in the article,
we could add them as well, to a maximum of six.
A note about autocomplete: Don't worry if QUODLIBET cannot autocomplete your
answer. QUODLIBET will attempt to autocomplete any text answer you supply.
However it has two different policies with regard to what it does when given input
that it cannot autocomplete. When entering entity data (genes, enzymes, etc.) that it
cannot autocomplete it will pretty much accepts whatever you give it. When
supplied with naturopathic data that it does not have in its database that it cannot
autocomplete it will prompt you to verify that you want to add the agent to the
database.
Finally, if we look below we see the PubMed article ID number already added to the
form in its proper field. Every natural product tagged in QUODLIBET must have a
PubMed referenced article associated with it.
There it is: You've surfed PubMed, found a relevant citation, and tagged it to a
naturopathic agent, all with less than five clicks of your mouse.
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ADDING NEW AGENTS TO THE DATABASE
Entering most common naturopathic agents triggers an autocomplete response,
indicating that QUODLIBET has these agents in its database. However entering rare
or uncommon entities may not prompt an autocomplete, most like indicating that
QUODLIBET does not contain an entry on these agents. Enter these anyway, since
part of our job is to make the QUODLIBET database ever-‐smarter.
Most times pressing the Associate Agent button tells QUODLIBET to add this
association (the link between these agents, the gene-‐protein entity and the PubMed
ID) to its database. If everything pans out the ubiquitous QUODLIBET Thank You
pop-‐up screen will greet you.
In cases where QUODLIBET does not recognize an agent it replies with a pop-‐up
declaring that the new agents were not found.
However as we will see it is willing to learn! If you scroll down, you will see a
second message screen that advises you that QUODLIBET did not find an exact
existing entry for one or more agents.
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Bottom of the Associate Agent Thank You pop-‐up: New Agent found.
Would you like QUODLIBET to add this agent(s) to its database and link these
entities and PubMed Reference to it? Since we are interested in having these items
in the database, we tick off the checkboxes and press the Yes, Add The New Agents
button.
At this point QUODLIBET again advises that we are in test mode so nothing is really
being saved here. However the status report is as if the data was really saved.
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PARTIAL MATCHES
QUODLIBET will also check its database for partial agent matches and present you
with a menu of possible matches for your consideration.
Again, normally pressing the Yes, Add This New Agent button will save any data that
you check off for this agent, but as your are a guest editor it just pretends to do so.
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PROFILING NATUROPATHIC AGENTS
One benefit of a totally integrated knowledge platform like QUOLIBET is that data
can be enriched on many different levels. In addition to linking natural products to
genes or proteins, we can also provide encyclopedic background material on natural
products and agents, such as descriptions, reference and outside links. This
information becomes available when a user clicks on a green Natural Products node
to display information on the references linking this agent to that gene or protein.
At that time QUODLIBET checks its internal database to see if there are any profile
entries on that natural product, if so, they are displayed as links in the pop-‐up.
All agent profiles are linked to the 'tag' for that agent, a behind-the-scenes number
that QUODLIBET threads throughout the program. You never really see any of this, but
this fact can help explain one basic fact: You can only write profiles for agents that are
in the QUODLIBET database of agents, since every profile must be linked to an agent,
which is in turn linked to its ID number, which in turn links it to QUODLIBET.
ADDING TO AN EXISTING AGENT PROFILE OR CREATING A NEW ONE
To work with an agent profile, begin by clicking Naturopathic Agents link (mortar
and pestle icon).
The Naturopathic Agents Icon.
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From the Dashboard, click the List Naturopathic Agents Link
The 'List Naturopathic Agents' link
Select a naturopathic agent from the list and click on it. This will open up the
naturopathic agent profile informatics popup. If you scroll down, you will see a text
entry field. This is where you can add/edit information on the naturopathic agent.
The Naturopathic Agent text entry field.
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. QUODLIBET uses a very cool text editor called TinyMCE. TinyMCE is a WYSIWYG
(what you see is what you get) editor that really allows for even inexperienced
editors to create and format great looking text. If you've ever made a headline or
converted some text to italics in Microsoft Word, you'll enjoy TinyMCE.
We'll start off by loading an already existing article and messing around with that.
From the List Naturopathic Agents screen, click on 'iodine.' At the top of the popup
you will see the current text on Iodine. This is what a non-‐editor user sees when
they click on this information popup.
Edit Naturopathic Agent Profile pop-‐up.
Scroll to the bottom and you will see the text entry field, in this case pre-‐popualted
with the current entry on iodine (entries without any text at this point would be
blank). Here you can work on the entry, then save your results.
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TINY MCE
• New Document: Clears the entry field.
• Bold, Italic, Underlined Font Style: Highlight your text and use these 3 buttons to
make text bold, italic, underlined, or strike-‐through.
• Left Adjust, Center, and Right Adjust Text: Highlight your text and these 3 buttons
to adjust text.
• Font Size: To make your article interesting, highlight your text and use this drop-‐
down menu to create a variety of different font sizes.
• Text Format for Size and Headings: To make your article interesting, highlight
your text and use this drop-‐down menu to create a variety of different styles of
headings with different attributes. You can use this to quickly make text large,
bold, italic and so on.
• Cut, Copy and Paste: Highlight your text and use these 3 buttons perform these
functions.
• Bulleted List, Numbered List: Highlight your text and use these 2 buttons create
these types of lists.
• Indent Text left, Indent Text Right: Highlight your text and use these 2 buttons
indent your text.
• Undo, Redo: This goes back or redoes your most recent action.
• Link, Unlink, Anchor, Insert Image: To insert or edit a link, select the linked text
and press this button. A pop-‐up dialog displays that lets you enter details about
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the link. Unlinking removes the hyperlink. To insert an image, place the cursor
in the desired location and press this button. A pop-‐up dialog box will appear
that lets you enter in the Image URL and other information about how the image
will display.
• HTML, Preview: Clicking the HTML button let's you work directly withthe HTML
of the entry. Only of use to seasoned programmers. Preview opens up the entry
in a new window, not really needed (the main window is a preview) unless you
are working directly with the HTML code.
• Select Text Color, Select Text Background Color: Select the color of your text. This
drops down to give you a choice of colors.
• Insert Date, Insert Time: Inserts date or time at insertion point.
• Toggle Spell Check: Turns spell check on or off.
• Insert horizontal rule: Applies a horizontal line
• Subscript: Converts highlighted text to subscript
• Superscript: Converts highlighted text to superscript
• Insert Custom Character, Emotions: Inserts special characters or emoticons
Play around with the entry text. Try different formatting effects, etc. Don't worry, it
will not be saved to the server.
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THE QUODLIBET COMMUNITY
We hope that this guide has peaked your curiosity about becoming a full-‐time
QUODLIBET editor. Systems like QUODLIBET evolve into a community of knowledge
workers intent on producing an exemplar of modern knowledge, a type of work that
is best done singularly, but in a highly collaborative way.
THE QUODLIBET FORUMS
Clicking on the Go To Forums ink (the 'speech balloon' icon) sends you to the
QUODLIBET Forums
The Quodlibet Forums Icon
The Forums are organized into two basic categories, threads for users and threads
for editors. Anyone can read the threads, but it is best to register (simple and
secure) so that if you have any problems you can post about them and hopefully get
help.
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QUODLIBET Forums
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ADDENDUM: THE KEGG MAPS PROJECT
Unlike inert hand drawn maps, such as those produced through KEGG (Kyoto
Encyclopedia of Genes and Genomics) once entered into QUODLIBET these maps will
be able to perform network calculations. Also, unlike other metabolic maps,
QUODLIBET maps are enriched with addition data about naturopathic agents capable
of influencing the expression and function of clusters and individual components of the
graph.
Current plans for QUODLIBET initiatives call for:
• The conversion of KEGG (Kyoto Encyclopedia of Genes and Genomics) maps into
QUODLIBET format. Thus, this part of the project is a bit of a no-‐brainer: One
needn't have to do the elemental work of constructing maps de novo; the KEGG
group has done a lot of that for us.
• The development of the agent profile database. This is map-‐independent.
• These and more are being discussed on the QUODLIBET Forums
COPYING KEGG MAP DATA INTO QUODLIBET
The procedure for working on the conversion of a KEGG map to QUODLIBET map is
straightforward: Once you are established as a fully functioning Editor, you can:
• Latch on to an ongoing KEGG conversion project. Each map has its own thread
on the Forum. You can also join a map project by contacting one or more of the
curators for the map, listed underneath the map descriptive paragraph.
• Propose a new map project. There is also a special thread for discussing this as
well
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Opening up the KEGG map for a QUODLIBET pathway.
A link to the existing KEGG map is provided at the end of the descriptive paragraph.
Clicking this link will open up a new window (not a pop-‐up) and display the KEGG
map for this pathway. As one might suspect KEGG does not have a map for the
Sandbox, but a lot of the Sandbox is based on the KEGG Notch Signaling system, so
this is what the KEGG link goes to.
KEGG Notch Signaling Pathway.
KEGG maps are great but they cannot 'compute' as a network. Many of the node
elements are hyperlinked and lead to further information. However for most of our
use, we will simply be 'hovering over' an entity with our mouse to observe if the
node has any constituent parts. As discussed a node can contain information about
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other genes that are associated with it, these are often synonyms, variants or
intermediates
Hovering over a KEGG node provides further information.
In this case hovering over the Dvl (Disheveled) node shows that Dvl is actually
composed of three constituents: DVL1, DVL2, DVL3. Thus if we were to add Dvl to
our map we would create a new node named Dvl and add the three other labels as
constituents. There is no need to actually do this: just click on Dvl in the Sandbox
while in edit mode and you will see that it has already been added in this way.
If you compare elements of the KEGG Notch map with parts of the QUODLIBET
Sandbox you can glean a lot about when certain things are done better one way or
another. For example, KEGG clusters PSE2/PSEN/NCSTN/APH-‐1 together as Gamma
Secretase Complex. We did a similar thing by creating a Port Node for these four
genes. You can also see the direction of many of the edges in the KEGG diagram.
Like QUODLIBET KEGG uses a normal arrowhead for a regular directed edge.
However KEGG uses 'T' arrowheads for inhibitory edges versus QUODLIBET, which
uses an inverted arrowhead. You can learn more about how to best accomplish a
particular conversion, and perhaps even get a suggestion or two, by visiting the
Forum for the map you are working on.
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FINAL THOUGHTS
I've enjoyed my time spent developing this application, and I'm certain that there is
much yet to do. For example, bringing most of the network analytics out to the user
still remains to be done, although some basic depictions are in place (i.e. changing
node color in response to page-‐rank and adjacency). However, what needs to occur
now is the development of content. I created three maps simply because I needed
something to base the program on. However, I've enjoyed my time added nodes and
other stuff (you can see my work mostly on the MAPK Kinase Cascade map). We
need many more maps and they need to be linked to generate the bigger 'grand
graph'. Thus I now feel comfortable enough to release this to the wider community,
knowing that I must stay close in order to plug the leaks and cover up the holes that
will undoubtedly appear once others start to use the application.
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It will be easy for some to look at what has been done, perhaps click on a map or two
and move on. One could only wonder if that response had occurred in the early days
of Wikipedia. Applications like Wikipedia and QUODLIBET need to be nourished in
their early days; a parent normally doesn't complain when their toddler doesn't do
the help with the dishes; there is time for that lesson in the future. Yet there is a
major, if unrecognized, advantage of working in these types of knowledge building
environment: you get amazingly smarter with information that seems to build on its
own context.
The slogan I chose for QUODLIBET was 'Networking the Vis.' I believe it can be done
and doing it will make us better healers. We owe nothing less to out clients and
ourselves.
See you on the Forums.
Peter D'Adamo