IPA Summer Release 2014

What’s New in the IPA Summer Release (June 2014)

With the IPA Summer Release you can explore how endpoints of Canonical Pathways may be increased or decreased based on activation or inhibition of molecules within that pathway.

Canonical Pathways in IPA have historically displayed disease and functional endpoints as “text boxes”; now, these endpoints can be used to interactively visualize the directional impact the pathway exerts upon them.

In this release of IPA, diseases and functions on Canonical Pathways are interactive and can be used by the Molecule Activity Predictor (MAP) to simulate the effect on disease or function.

Interactive Disease & Function nodes on Canonical Pathways. In this zoomed-in portion of the “Role of NANOG in Mammalian Stem Cell Pluripotency” Canonical Pathway, there are interactive nodes for “Endoderm specification”, “Mesoderm differentiation”, “Ectoderm Differentiation”, “Trophoectoderm differentiation”, “Pluripotency” and “Regulation of telomere length”. Based on the differential expression of molecules in a differentiating cardiomyocyte dataset that was overlaid on the pathway, the first three functions (colored orange) are predicted to be increased, while the latter two (colored blue) are predicted to be decreased.

Interactive Disease & Function nodes on Canonical Pathways. In this zoomed-in portion of the “Role of NANOG in Mammalian Stem Cell Pluripotency” Canonical Pathway, there are interactive nodes for “Endoderm specification”, “Mesoderm differentiation”, “Ectoderm Differentiation”, “Trophoectoderm differentiation”, “Pluripotency” and “Regulation of telomere length”. Based on the differential expression of molecules in a differentiating cardiomyocyte dataset that was overlaid on the pathway, the first three functions (colored orange) are predicted to be increased, while the latter two (colored blue) are predicted to be decreased.

Discover & explore diseases or functions that are relevant to molecules on a pathway or network

Quickly discover diseases or functions that are biologically (and statistically) relevant to a set of molecules on a network or pathway. Automatically connect diseases or functions of interest to the relevant molecules and use MAP (Molecule Activity Predictor) to simulate how activated or inhibited molecules are likely to affect the disease based on findings in the Ingenuity Knowledge Base.

Grow to Diseases & Functions feature. Selecting the Grow menu (in BUILD tools) and clicking on the Diseases & Functions tab displays a table which shows the relevant diseases or function that can be added to the pathway, ranked by statistical significance (by Fisher’s Exact Test) with respect to the set of molecules in the network in the right panel. When one or more is selected and the apply button is pressed, they will automatically be added and connected to the network (continued, see below).

Grow to Diseases & Functions feature. Selecting the Grow menu (in BUILD tools) and clicking on the Diseases & Functions tab displays a table which shows the relevant diseases or function that can be added to the pathway, ranked by statistical significance (by Fisher’s Exact Test) with respect to the set of molecules in the network in the right panel. When one or more is selected and the apply button is pressed, they will automatically be added and connected to the network (continued, see below).

grow to disease 2

Grow to Diseases & Functions feature (continued). You may filter the list of significant diseases or functions to focus on those of interest. In the example shown, two keywords were used to filter the list resulting in two matching functions that were added to the pathway at the right. Note that you can use the wildcard (asterisk) to create a more permissive filter. In this example, MAP automatically predicts the added functions are increased based on the activity of the molecules to which they are connected (orange color corresponds to a prediction of increase).

Configure Comparison Analysis heat maps to focus on rows of interest.

Quickly focus on diseases, functions, or Canonical Pathways of interest when viewing a comparison analysis heat map. Now you can narrow the list of diseases, functions, or pathways that are shown in the heat maps in IPA Comparison Analysis. In the Disease and Functions tab, you can now filter on major categories or on specific individual diseases and functions as shown in the figure below.

focus on particular

Focus on particular diseases & functions in Comparison Analysis. In this example, the heat map is being filtered (by clicking the FILTER button at the top left) to display only functions in the category “Cardiovascular System Development and Function”. In addition it is filtered to display only those rows where at least one column has an absolute z-score of 2 or greater.

Likewise, you can filter Canonical Pathways in their corresponding heat map.

Focus on particular Canonical Pathways in Comparison Analysis. In this example, the heat map is being filtered (by clicking the FILTER button at the top left) to display only Metabolic Pathways as well as the pathways specifically associated with Cardiovascular Signaling. You can display the filters in a tree view (as shown) or sorted alphabetically by name (click the List View radio button). The heat map is also being filtered to display only those rows where at least one column has a -log(p-value) of 3 or greater, which is equivalent to a p-value of <= 0.001.

Focus on particular Canonical Pathways in Comparison Analysis. In this example, the heat map is being filtered (by clicking the FILTER button at the top left) to display only Metabolic Pathways as well as the pathways specifically associated with Cardiovascular Signaling. You can display the filters in a tree view (as shown) or sorted alphabetically by name (click the List View radio button). The heat map is also being filtered to display only those rows where at least one column has a -log(p-value) of 3 or greater, which is equivalent to a p-value of <= 0.001.