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differential_signaling [2021/01/27 14:41] – [Pathways] kriandifferential_signaling [2021/01/29 22:14] (current) – [Differential signaling form] krian
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 ====== Differential signaling ====== ====== Differential signaling ======
-HiPathia allows us to compute a signal value through a chosen signaling pathways and for each one of our data samples.  +HiPathia allows inferring a value of signal transduction activity through any of the different circuits defined in any signaling pathway for each sample in the analyzed dataset, based on the gene expression values.  
-Therefore, it allows us to compare the signal value between different conditions.+Therefore, the same way that in a transcriptomic experiment differential expression between two conditions is conducted, HiPathia allows comparing the signal transduction activities between different conditions in a **differential signaling** asessment.
 We can:  We can: 
-  * Compare either two groups, for example a normal Vs tumor samples. +  * Compare two conditions, for example normal vs tumor samples. 
-  * Correlate the path value with a continuous variable.+  * Correlate the signal transduction activity with a continuous variable.
  
 The tool can be accessed from the main menu bar, by clicking on the //Differential signaling// button, see [[workflow|Workflow]] for further information. The tool can be accessed from the main menu bar, by clicking on the //Differential signaling// button, see [[workflow|Workflow]] for further information.
 {{ :differential_signaling_form.png?nolink |}} {{ :differential_signaling_form.png?nolink |}}
 ===== Differential signaling form =====  ===== Differential signaling form ===== 
-The main page of the tool is its filling in form. This form includes all the information and parameters that the tool needs to process a Differential signaling study. The form is divided in different panels:+The main page of the tool is its filling form. This form includes all the information and parameters that the tool needs to process a Differential signaling study. The form is divided into different panels:
 ==== Input data panel ==== ==== Input data panel ====
 In the input data panel, we must introduce the expression data. In the input data panel, we must introduce the expression data.
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 {{ ::pathwaysreport1.png?nolink |}} {{ ::pathwaysreport1.png?nolink |}}
   - In the upper-right part of the visualization tool, all selected pathways from the differential signaling form are shown along with one or two arrows. These arrows indicate whether in one of the "Effector circuit" within each pathway a differential activation pattern between the two compared groups have been found.\\ The arrows will be colored if the differential activation is significant after the p-value adjustment (or unadjusted p-value, if the "Unadjusted" parameter has been selected) and depicted in grey if it isn't.\\ The arrow will point up or down if an up-regulation or down-regulation of the signal occurs between the circuits within that pathway.\\ The meaning of this up or down-regulation depends on the comparison performed, that normally would be case vs. control (comparison between selected class from the design file : condition 1 Vs condition 2).\\ Only one arrow is shown if all the effector circuits are whether up or down-regulated.{{ ::pathwaysreport2.png?nolink |}}   - In the upper-right part of the visualization tool, all selected pathways from the differential signaling form are shown along with one or two arrows. These arrows indicate whether in one of the "Effector circuit" within each pathway a differential activation pattern between the two compared groups have been found.\\ The arrows will be colored if the differential activation is significant after the p-value adjustment (or unadjusted p-value, if the "Unadjusted" parameter has been selected) and depicted in grey if it isn't.\\ The arrow will point up or down if an up-regulation or down-regulation of the signal occurs between the circuits within that pathway.\\ The meaning of this up or down-regulation depends on the comparison performed, that normally would be case vs. control (comparison between selected class from the design file : condition 1 Vs condition 2).\\ Only one arrow is shown if all the effector circuits are whether up or down-regulated.{{ ::pathwaysreport2.png?nolink |}}
-  -  In the lower-right part of the tool will appear all the circuits in which a pathway (previously selected on the upper part -1-) can be decomposed. Once any of the circuit is clicked the nodes and interactions (edges) that form part of this circuit are highlighted in the pathway viewer (), One example might be the red-highlighted circuit on the figure below.{{ ::effectorcircuithl.png?nolink |}}+  -  In the lower-right part of the tool will appear all the circuits in which a pathway (previously selected on the upper part -1-) can be decomposed. Once any of the circuit is clicked the nodes and interactions (edges) that form part of this circuit are highlighted in the pathway viewer, One example might be the red-highlighted circuit on the figure below.{{ ::effectorcircuithl.png?nolink |}}
   - In the visualization part there are two types of objects, the nodes and the edges.{{ ::pathwaysreport3.png?nolink |}}   - In the visualization part there are two types of objects, the nodes and the edges.{{ ::pathwaysreport3.png?nolink |}}
-    * The nodes represent the different proteins or metabolites that are responsible on passing the signal from the previous node to the next one. As commented before, the nodes can be plain or complexes. In the former it is only necessary the presence of one protein (although that same function can be done by several proteins), while in the complex ones it is necessary the presence of two or more proteins to pass the signal through.\\ The color on the nodes are the result of a differential expression analysis on the gene/s involved on performing that node's function.+    * The nodes represent the different proteins or metabolites that are responsible of the transduction of the signal from the previous node to the next one. As commented before, the nodes can be plain or complexes. In the former it is only necessary the presence of one protein (although that same function can be done by several proteins), while in the complex ones it is necessary the presence of two or more proteins to pass the signal through.\\ The color on the nodes are the result of a differential expression analysis on the gene/s involved on performing that node's function.
     * The edges represent how the interactions between the different nodes are.\\ If the edge is an arrow then the previous node will be activating the next one, while if it ends with a vertical bar is the former node will inhibit the functionality of the following node. This interactions may be depicted in red or blue depending on the circuit they form part of (whether they are up-regulated or down-regulated). It may occur, that two or even three colors for a same edge are shown, but this only happens when a circuit is not yet selected on the lower-right part of the tool.\\ Once an certain circuit is selected all its edges will be colored in the same color depending on the result of the differential signaling activation analysis.{{ ::pathwaysreport4.png?nolink |}}     * The edges represent how the interactions between the different nodes are.\\ If the edge is an arrow then the previous node will be activating the next one, while if it ends with a vertical bar is the former node will inhibit the functionality of the following node. This interactions may be depicted in red or blue depending on the circuit they form part of (whether they are up-regulated or down-regulated). It may occur, that two or even three colors for a same edge are shown, but this only happens when a circuit is not yet selected on the lower-right part of the tool.\\ Once an certain circuit is selected all its edges will be colored in the same color depending on the result of the differential signaling activation analysis.{{ ::pathwaysreport4.png?nolink |}}
   - The top part contains the title of selected pathway,by clicking on this button {{::keggsource.png?nolink|}} you can see the original source of this pathway.\\ {{ :pathwaysreport4_6.png?nolink |}}   - The top part contains the title of selected pathway,by clicking on this button {{::keggsource.png?nolink|}} you can see the original source of this pathway.\\ {{ :pathwaysreport4_6.png?nolink |}}
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   * The first section below there is a link to download the calculated circuit activity values. This matrix file indicates for each effector circuit the level of activation calculated using Hipathia method for each sample.{{ ::circuitvalue.png?nolink |}}   * The first section below there is a link to download the calculated circuit activity values. This matrix file indicates for each effector circuit the level of activation calculated using Hipathia method for each sample.{{ ::circuitvalue.png?nolink |}}
   * The Heatmap plot represented on the hipathia results page is a heatmap of the activation values from the most differentiated effector circuits (rows) between groups along with a clustering of the samples (columns). This plot allows to observe if its possible to differentiate the groups that are compared according to its effector circuit activation values.\\ The colors depicted here indicates the level of activation for the different circuit in each sample, being the bluish ones those with lower activation levels and the reddish the highest ones (e.g. if a given cell of the heatmap is blue would indicate that this particular effector circuit is poorly activated in that determined sample) {{ ::heatmap.png?nolink |}}   * The Heatmap plot represented on the hipathia results page is a heatmap of the activation values from the most differentiated effector circuits (rows) between groups along with a clustering of the samples (columns). This plot allows to observe if its possible to differentiate the groups that are compared according to its effector circuit activation values.\\ The colors depicted here indicates the level of activation for the different circuit in each sample, being the bluish ones those with lower activation levels and the reddish the highest ones (e.g. if a given cell of the heatmap is blue would indicate that this particular effector circuit is poorly activated in that determined sample) {{ ::heatmap.png?nolink |}}
-  * The next plot on the Hipathia report corresponds to a Principal Component Analysis plot. This figure is useful to determine if the activation levels of the pathways calculated with Hipathia are able to differentiate between the two groups that are being compared. {{ ::pca.png?nolink |}}+  * The next plot on the Hipathia report corresponds to a Principal Component Analysis plot. This figure is useful to determine if the activation levels of the signaling circuits calculated with Hipathia are able to differentiate between the two groups that are being compared. {{ ::pca.png?nolink |}}
   * In the section below there is a table (that can be downloaded) with the results of the differential activation analysis. This table indicates for each effector circuit whether or not there is a different level of activation depending on the group the samples belong. {{ ::circuitsig.png?nolink |}}   * In the section below there is a table (that can be downloaded) with the results of the differential activation analysis. This table indicates for each effector circuit whether or not there is a different level of activation depending on the group the samples belong. {{ ::circuitsig.png?nolink |}}
     * **circuit/term**: Code identifying the circuit consisting in the name of the pathway to which it belongs and the effector (last) node of the Circuit (//pathway Name : Effector//).     * **circuit/term**: Code identifying the circuit consisting in the name of the pathway to which it belongs and the effector (last) node of the Circuit (//pathway Name : Effector//).
differential_signaling.1611758509.txt.gz · Last modified: 2021/01/27 14:41 by krian