Tool description and tutorials
Exploitative Analysis. The system provides two major functions for
the exploitative analysis of the data set. The former is the visualization of the
phenotypic network and the latter is the visualization clustering of the
Query Analysis. The tool provides two different types of queries.
The former, called simple query, allows the user to investigate connections
of a specific element in the network. Given a node and a threshold, the tool
shows all its neighbours divided into four categories: nanomaterials, diseases,
drugs and chemicals. For each phenotypic entity in the query output the tool
highlights its position in the ranking of the neighbours and the information
indicating whether the connection is already known in the literature or not.
Moreover, the tool displays the connection distributions for the query input.
The latter, called conditional query analysis, allows the users to query the
network by applying different filters. The user can specify more than one item
for each data type, the level of similarity necessary to report a connection
between two selected items, the number of items that must be in the same
resulting cliques and the number of query items being connected to the other
nodes in the sub-network. The tool gives two different outputs: firstly for each item, it
creates a sub-network of all the elements connected to the input phenotypic
entities with a connection stronger than the selected threshold; secondly it
analyses the sub-networks and founds out all the patterns (cliques) of three or
four different types of phenotypic entities each other significantly interconnected.
The cliques are then clustered with respect to the nature
of the connection between two items.
Network Browser Tutorial
The network browser tool allows the user to display and interact with the network.
Due to the high dimensionality of the network the tool allows the user to display only part of it.
How do I perform the simple query analysis?
- Click on Browse in the navigation bar
- The tool, by default, displays the subnetwork of all the elements
associated to WCCo with threshold 1%
- The network browse panel is available on the left side of the screen.
It can be used to modify the network layout or filter out edges and nodes
of the network
- Network statistics are showed on the right part of the screen
- Nodes can be clicked for more details
INSIdEnano network browser
Querying the network
In order to visualize the information related to a specific node the user can follow these steps:
- Click on the search button in the network browser pane
- Insert the name of the node to investigate (in the example TIO2T20)
- Specify the percentage of top interaction to visualize
- Press on the button "Update network" to visualize the result
Performing a query within the network
Displaying complete subnetworks
The user can also display the subnetwork of a specific class of nodes for,
example nanomaterials. In order to perform this operation, the user must follow
the following steps:
- Open the search tab in the network browser panel
- Select the category of objects to display
- Click on the "Update network" button
Subnetwork of all nanomaterials
Simple query tutorial
How do I perform the simple query analysis?
- Click on Simple Query in the navigation bar
- Choose the name of the element from the element list
- Insert the connection strength threshold
- Click on Search
Query Example: Parkinson Disease with threshold 50%
Simple query form
Results will be displayed on three tabs:
- The first one reports all the entities connected to the given
element listed by category (nanos, drugs, chemicals and diseases)
- The second one gives information about the connection
distributions. We can see that Parkinson has 75% of
positive and 25% of negative connections with nanomaterials in the
- The third one gives information about the distribution weights.
Simple query results
The user can investigate the result section by:
- Sorting the elements by their position in the ranking or sort the
elements based on the fact that the connection is known in literature
or not. For example, sorting drugs by the known connection we find
'levodopa' to be connected to Parkinson with rank 9.
- Clicking on the name of the element more information is available.
The tool displays their ATC code, unique IDs and gives links
to external resources in case of drugs.
- Clicking on the levodopa Wikipedia link we discover that levodopa
is used to increase dopamine concentrations in the treatment of
- The colours of the element names give information about the positive
(red) or negative (green) type of connection
Simple query results
Conditional query tutorial
How do I perform the conditional query analysis?
- Click on Conditional Query in the navigation bar
- Insert the subset of elements to investigate divided by the four
categories: nanomaterials, drugs, diseases and chemicals.
Insert the connection strength threshold
Insert the "minimum connected elements" threshold. This threshold allows
to control the number of neighbours of the elements of interest to be
selected. In particular, it indicates how many of the elements of interest
are to be connected to a neighbour to consider it part of the analysis.
Insert the "minimum elements in cliques" threshold. This threshold
allows to control the number of elements of interest to be in the final cliques.
Click on Run conditional query
- N.B.: insert elements of at least two categories
- Insert one, more than one, or all the element of a specific category
- In order to insert all the element of a category,
click on the "include all" button and switch it from OFF to ON:
Conditional query form
Conditional query output
The output is displayed in three different tabs:
The tab named "Results" contains the list of cliques. The panel is organized
in the following manner:
- The left panel shows the types of cliques. Cliques are categorized
based on the classes of the objects that they contain. The user can choose
the group to visualize by clicking on its button
- The "Matching cliques" panel reports a table with the list of cliques.
- Cliques can be filtered based on the fact that at least one of the
interaction represented are already known in literature
- Moreover, the list can be filtered based on the sign of the edge
between two object of different classes
- Elements can be searched in the table by typing their name in the search field
- By clicking on a row representing the cliques another panel named clique
information appear. It gives information regarding the kind of connection
between the nodes.
- In this tab each entity name is clickable in order to show its details
- Tables can be exported by using the data export panel
Conditional query results
Clique information panel has four buttons that can be used to further investigate the selected clique.
- The first one highlights the clique in the subnetwork obtained from the analysis
- The second one shows a table containing
information about the common genes affected by all element in the clique.
A green arrow means that the gene is upregulated by the element; a red
arrow means it is downregulated by the element; two black arrows means that
the genes is affected but we do not know if it is up or down regulated.
- The third one shows the genes affected by each
element of the clique, divided in groups. The groupings come from the gene
sets collection of MSigDB. The Jaccard index has been evaluated for each
set of the MSigDB database and the set of genes affected by each element.
A threshold based on this index can be used for visualization purpose.
Only sets of genes with Jaccard index higher than the one specified will
be displayed. Each set name is expandable in order to inspect how the
genes it contains behave with respect to the phenotypic entity.
- This button allows to perform a PubMed search by
using the elements in the clique. The default query is displayed. The user can
either use the default query or change it before submitting to PubMed.
1. Highlighting a clique in the network
2. Gene enrichment information
3. Pathway enrichment information
3. PubMed query interface
This tab shows the subnetwork obtained from the conditional query analysis. The user can:
- control the network from the control panel. It is divided into six main parts:
- zoom in and out the network
- network layout algorithms
- node size: the weighted size of the is the node degree.
- edge thickness: the weighted thickness is the strength of
correlation between the connected nodes
- edge filter
- node filter
- visualize the network and interact with it. One can for example click and drag
the nodes or display their names by hovering the mouse pointer
- display detailed information about a node by clicking it
- inspect the network statistics
Conditional query subnetwork tab
This tab allows the user to visualize various statistics about the resulting cliques.
In particular, it counts how many time a couple of objects are connected in the
cliques. The user needs to specify the two classes of objects to investigate
and the tool returns a bubble plot where the bubbles radii indicate the number
of times these two objects are connected.
Conditional query results statistics
Clustering analysis tutorial
The Cluster Analysis panel gives the possibility to investigate how
nanomaterials, drugs, disease and chemical are grouped each other and which
genes are most important to each of them.
How do I perform the clustering analysis?
- Click on Cluster Analysis in the navigation bar
- Choose the kind of items to investigate, for example nanomaterials. The tool displays the list of all nanomaterials grouping based on their gene expression value
- The user can click on a nanomaterial name to obtain more information in the pane on the right
- The information panel contains information about the nanomaterials gene expression experiments. Moreover, the list of up and down regulated genes coming from the differentially expressed analysis is displayed
- By clicking on the name of the genes its Gene card webpage is displayed.
The development of INSIdEnano was supported by the European Commission (FP7-NANOSOLUTIONS, Grant Agreement No. 309329).