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--- worked_example3 [2016/02/08 11:21] – created dcrespo
+++ worked_example3 [2017/05/24 15:27] (current) – external edit 127.0.0.1
@@ Line 1: / Line 1: @@
 ====== Worked example: ======
-===== Data and data source: =====
+===== Data and data source =====
-In this example we use gene expression data from NSCLC HCC4006 (EGFR<sub>m</sub>), downloaded from [[http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57156|GSE57156]].
+In this example we use gene expression data from NSCLC HCC4006 (EGFR<sub>m</sub>).
-====== Steps: ======
+The file can be downloaded from this link:
-  * Log in **PathAct**. //Figure 1// shows the main webpage and how to access.
+{{:hcc4006_mutant_dmso.txt|hcc4006_mutant_dmso.txt}}
-{{ :intro2.png?600 |}}
+And was obtained from [[http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57156|GSE57156]] project.
-**Figure 1: A:** Welcome screen of PathAct: **I )** Start box. **II )** Login box. **III )** Sign up button. **IV )** Help pages. **B:** Screenshot from login box (marked with II). **C:** Screenshot from sign up box. D: Help menu.
-  * Load example 2 by pressing //Load example file 2// button from the Expression matrix files panel. Once loaded, click on the //pathact_example_2.txt// button and load it. //Figure 2// shows the overview of the PathAct working page.
+===== Steps: =====
+  * Log in **PathAct** using the login button on the top right corner, the login panel will appear.
-{{ :intro.png?600 |}}
+{{ :login.png?400 |}}
-**Figure 2:** Overview of PathAct.** A:** Profile section.** B:** Expression matrix files panel (allows load and select data files).** C:** CellMaps visualizer. An interactive visualizer that shows the pathways and perturbations.** D:** Pathway list.** E:** Gene list panel. It allows customize the activity of the node. **F:** Circuit list for a given pathway. **G:** Drug targets panel (only for drug assisted functionality). It shows the side effect of selected drugs.** H:** Related drug list panel. Once selected a gene, PathAct propose drugs with the same target. Configure target actions button allows customize the impact of drug effect. **I:** Last update gene list panel. A list showing the last gene modifications.
+  * You can also login as anonymous using the start button.
+{{ :start.png?400 |}}
-  * In this example we simulate the effect of treating cells with Erlotinib (FDA approved EGFR inhibitor for treatment of NSCLC EGFR mutant). We modify the target actions fixing: Agonist = 0.8 and Antagonist = 0.1 (mechanisms of action of Erlotinib on its targets).// Figure 3// shows how modify the expression of those genes.
+  * Upload the file as is shown in the [[Upload your data|Upload your data]] section and launch a job with that file.
+{{ :ex3run.png?900 |}}
+  * A job will appear on the right and will be processed.
+{{ :ex3running.png?600 |}}
+  * Once finished, click on it to open the view window.
+ {{ :ex3ready.png?600 |}}
+  * The view window will appear.
+ {{ :view.png?800 |}}
+  * In this example we simulate the effect of treating cells with Erlotinib (FDA approved EGFR inhibitor for treatment of NSCLC EGFR mutant). We modify the target actions fixing: Agonist = 0.8 and Antagonist = 0.1 (mechanisms of action of Erlotinib on its targets).// Figure 1// shows how modify the expression of those genes using the setting panel.
+  *  To open the settings panel click on the //Settings// button located at the top right corner.
+ {{ :ex3settings.png?400 |}}
 {{ :gse57156_3.png?600 |}}
-**Figure 3:** Gene signal modification. **A:** Screenshot of gene selection panel. Note how the drug list appears when we select any gene. **B:** We modify the effect of drug action on its targets (in our case, agonist and antagonist, mark with red arrow and stars).** C:** Screenshot of gene selection panel after In Silico treatment with erlotinib. We have had to manually modify the expression of “EGFR - EGFR node” and “GRB2 EGFR node” because the drug annotations doesn't contain those targets.
+**Figure 1:** Gene signal modification. **A:** Screenshot of gene selection panel. Note how the drug list appears when we select any gene. **B:** We modify the effect of drug action on its targets (in our case, agonist and antagonist, mark with red arrow and stars).** C:** Screenshot of gene selection panel after In Silico treatment with erlotinib. We have had to manually modify the expression of “EGFR - EGFR node” and “GRB2 EGFR node” because the drug annotations doesn't contain those targets.
-CellMaps visualizer highlights modified genes to help locate them (//figure 4//).
+The visualizer highlights modified genes to help locate them (//figure 2//).
 {{ :gse57156_4.png?600 |}}
-**Figure 4: A:** ErbB signaling pathway. **B:** Detail of EGFR modification on the pathway. Note how CellMaps marks perturbed genes.
+**Figure 2: A:** ErbB signaling pathway. **B:** Detail of EGFR modification on the pathway. Note how the visualizer marks perturbed genes.
   * Perform the inhibition by pressing //update// button. Those pathways and circuits that have been modified are marked in bold. Red or blue arrows indicate if those changes are or not significant (overactivated path or repressed).
@@ Line 34: / Line 57: @@
 {{ :gse57156_11.png?200 |}}
-**Figure 5:** Pathway list aspect after perturbation. The panel marks those pathways (**A**) and circuits (**B**) which activation has been modified (bold). Significant modification is marked with red upwards arrows (over activity) and blue down arrows (repression).
+**Figure 3:** Pathway list aspect after perturbation. The panel marks those pathways (**A**) and circuits (**B**) which activation has been modified (bold). Significant modification is marked with red upwards arrows (over activity) and blue down arrows (repression).
-Pathways appear painted with red or blue connecting lines in the visualizer. In our example all lines are blue because our inhibition reduce the active level of all the circuit (//figure 6//). We show how EGFR inhibition ends in alteration of transcriptional programs that in our example stop cell growth.
+Pathways appear painted with red or blue connecting lines in the visualizer. In our example all lines are blue because our inhibition reduce the active level of all the circuit (//figure 4//). We show how EGFR inhibition ends in alteration of transcriptional programs that in our example stop cell growth.
 {{ :gse57156_5.png?600 |}}
-**Figure 6:** ErbB signaling pathway previous the perturbation (**A**) and after (**B**). Significant repressed circuits are painted in blue. **C:** Detail of Estrogen signaling pathway. **D:** CREB3 circuit  of Estrogen signaling pathway. Note how the circuit selection helps to visualize correctly the perturbed system.
+**Figure 4:** ErbB signaling pathway previous the perturbation (**A**) and after (**B**). Significant repressed circuits are painted in blue. **C:** Detail of Estrogen signaling pathway. **D:** CREB3 circuit  of Estrogen signaling pathway. Note how the circuit selection helps to visualize correctly the perturbed system.
-  * PathAct allows step by step perturbations. In our example we show Erlotinib resistance acquisition by a typical way, PTEN loss and constitutive activation of HER2 (ERBB2). //Figure 7// shows how system respond to alteration. The visualization of different paths remains simple and is showed in //figures 8 and 9//. Furthermore, circuit selection simplify user how the signal are propagated.
+  * PathAct allows step by step perturbations. In our example we show Erlotinib resistance acquisition by a typical way, PTEN loss and constitutive activation of HER2 (ERBB2). //Figure 5// shows how system respond to alteration. The visualization of different paths remains simple and is showed in //figures 6 and 7//. Furthermore, circuit selection simplify user how the signal are propagated.
 {{ :gse57156_6.png?400 |}}
-**Figure 7:** ErbB signaling pathway after the treatment with Erlotinib (**A**) and after adaptation (PTEN loss and HER2 activating mutation - **B**).
+**Figure 5:** ErbB signaling pathway after the treatment with Erlotinib (**A**) and after adaptation (PTEN loss and HER2 activating mutation - **B**).
 {{ :gse57156_7.png?600 |}}
-**Figure 8: A:** ErbB signaling pathway after the resistance acquisition to the treatment and previously (**B**). **C:** SAT5A circuit of ErbB signaling pathway. Note how by circuit visualization helps the interpretation.
+**Figure 6: A:** ErbB signaling pathway after the resistance acquisition to the treatment and previously (**B**). **C:** SAT5A circuit of ErbB signaling pathway. Note how by circuit visualization helps the interpretation.
 {{ :gse57156_8.png?600 |}}
-**Figure 9: A:** PI3K - Akt signaling pathway after second perturbation (resistance acquired to EGFR inhibitor).** B:** MAPK1 circuit of PI3K - Akt signaling pathway. Note how MAPK circuits are repressed and mTOR circuits are activated. **C:** C8orf44-SGK3 circuit of PI3K - Akt signaling pathway. Note how by circuit visualization helps the interpretation.
+**Figure 7: A:** PI3K - Akt signaling pathway after second perturbation (resistance acquired to EGFR inhibitor).** B:** MAPK1 circuit of PI3K - Akt signaling pathway. Note how MAPK circuits are repressed and mTOR circuits are activated. **C:** C8orf44-SGK3 circuit of PI3K - Akt signaling pathway. Note how by circuit visualization helps the interpretation.
-  * Activating ERK mutations constitutes another important mechanism of resistance to EGFR inhibitors. //Figure 10// shows how constant activation of ERK (MAPK1) offset EGFR inhibition and MAPK pathway is restored.
+  * Activating ERK mutations constitutes another important mechanism of resistance to EGFR inhibitors. //Figure 8// shows how constant activation of ERK (MAPK1) offset EGFR inhibition and MAPK pathway is restored.
 {{ :gse57156_10.png?600 |}}
-**Figure 10: A:** MAPK signaling pathway after second perturbation (resistance acquired to EGFR inhibitor by ERK activating mutation). Note how the circuit remains activated although EGFR remains inhibited.
+**Figure 8: A:** MAPK signaling pathway after second perturbation (resistance acquired to EGFR inhibitor by ERK activating mutation). Note how the circuit remains activated although EGFR remains inhibited.
-  * Finally, PathAct reports (//figure 11//) all the gene signal alterations and circuits log fold change, discriminating between significant or not (absolute FC > 2).
+  * Finally, PathAct reports (//figure 9//) all the gene signal alterations and circuits log fold change, discriminating between significant or not (absolute FC > 2).
 {{ :gse57156_9.png?400 |}}
-**Figure 11:** PathAct report. **A:** list of perturbed genes and final value of activation. **B:** ranked circuits by log fold change (base 10). Note how PTEN logFC are -Infinite (PTEN loss represents a complete depletion of PTEN - complete node inactivation). **C:** Fold change is used by calculate significance using 2 as threshold (log<sub>e</sub>2 = 0.6931472).
+**Figure 9:** PathAct report. **A:** list of perturbed genes and final value of activation. **B:** ranked circuits by log fold change (base 10). Note how PTEN logFC are -Infinite (PTEN loss represents a complete depletion of PTEN - complete node inactivation). **C:** Fold change is used by calculate significance using 2 as threshold (log<sub>e</sub>2 = 0.6931472).