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--- perturbation_effect [2019/08/08 13:20] – krian
+++ perturbation_effect [2021/01/26 16:10] (current) – update old results example ialamo
@@ Line 1: / Line 1: @@
 ====== Perturbation effect ======
-HiPathia also allows us, through this panel, to assay in silico the effect of knock-out and over-expression experiments in the signaling pathways. The knock out of a gene can be done for this single gene, or following the pattern established by the action of a drug targeting it.
+The mechanistic model implemented in HiPathia can also be used for the simulation of the effect that interventions, such as gene knock-out and over-expression perturbations, can have over signaling pathways. This simulation is carried out by changing the expression level of the gene(s) of interest, recalculating the resulting signaling profile in the simulated condition and comparing it to the original profile. Similarly, the effect of inhibitory or agonistic drugs can be simulated by decreasing or increasing the expression level of the target gene. This module of analysis brings the functionality of the [[https://academic.oup.com/nar/article/44/W1/W212/2499353|PathAct algorithm]] to the HiPathia application.
-Also allows you to **modify the expression value of a set of genes** and then check the effect that this change has in the signaling pathways. In this way, **you can simulate knock outs or over-expressions of one or several genes** or the **effect of a drug** in the activity of signaling pathways.
+Gene perturbations can be studied one at a time or simultaneously in combinations. In this way it is possible to check for the potential effect of drug combinations over the activity of signaling pathways in a given condition.
-Information about the drugs targeting the selected genes is provided, allowing to simulate their application and dose and see the changes in the signaling pathways.
+In this module, the effects of interventions over one specific condition (defined by the profile of gene expression of the sample) can be studied in an interactive manner. Thus, after uploading the gene expression profile of a sample, a pannel appears in which different genes can be selected and the typpe of interaction can be chosen by simulating an increase or decrease in their gene expressio levels in the sample. Alternatively, the effect of drugs (taken from [[https://www.drugbank.ca/|DrugBank]]) can be explored. The genes targeted by the selected drugs are set to the corresponding simulated state of activation or inhibition.
-The tool can be accessed from the main menu bar, by clicking on the //Perturbation effect// button.
+The **Perturbation effect module** can be accessed from the main menu bar, by clicking on the //Perturbation effect// button.
+{{ :perturbation_effect_form.png?nolink |}}
- ===== INPUT =====
+===== Perturbation effect form =====
+The main page of the tool is a form. This form includes all the information and parameters needed to process a perturbation effect study.
-The main page of the tool is a form. This form includes all the information and parameters needed to process a perturbation effect study. The form is divided in different panels:
+{{ ::perturbationeffectform.png?nolink |}}
-  * **[[Expression matrix file format |Expression matrix file]]** :
+The form is divided in different panels:
-Expression matrix provided by ourselves (see how to upload files in [[upload_your_data|Upload your data]]).
+==== Expression matrix file =====
+  * **[[Expression matrix file format |Expression matrix file]]** : Expression matrix provided by ourselves (see how to upload files in [[upload_your_data|Upload your data]]).
- ==== Sample ====
+{{ ::expmatrfile.png?nolink |}}
+When we select a gene expression file, the number of samples of this matrix will appear under the “File browser” button as shown below.
+{{ ::pertnumberofsamples.png?nolink |}}
+==== Sample ====
 Once the file is selected the column names of the expression matrix will be loaded in this panel, we have to select the column to proceed.
-{{ :persurbationeffect.png |}}
+{{ ::samplesperteffectform.png?nolink |}}
-[[job information| ==== Study information ==== ]]
+==== Study information ====
+This panel includes some parameters in order to identify and save our study.
+  * **Output folder**: If we want to reorganize our studies we can select the folder in which we want save our report. By default the study will be saved in the home in a folder named "Perturbation_effect_study-N", N is an integer number.
+  * **Study name**: We can give a name to our study. This is very useful to later identify it among the other studies listed in the //My studies// list.\\ The default study name is "Perturbation_effect_study-N", N is an integer number.
+  * **Description**: We can give a description to our study.
+{{ ::studyinfopereffectform.png?nolink |}}
+==== Run analysis ====
 Once the form has been filled in, press the //Run analysis// button to launch the study. Your study will be listed in the //My studies// panel.
+{{ ::runanalysis.png?nolink |}}
+Your study will be listed in the //My studies// panel, and a panel called //Browse my studies// will appear showing all your studies and their state. the new study will appear with a **queued** state then **running** state. If everything goes well, the state will be **done** after few minutes(depending on the inputs data and the availability of server).
+All study states are:
+  * **Queued**: The information has been processed and the study has been sent and waits to be processed.
+{{ ::queuedpereff.png?nolink |}}
+  * **Running**: The study is in progress, study can be cancelled using the stop button.
+{{ ::runingperteffect.png?nolink |}}
+  * **Done**: The study has ended and the results are available to visualize and download.
+  * **Cancelled**: The study was canceled before finishing.
+  * **Error**: Sometimes a study can stop returning a error message, you can report and contact us in order to help you to fix it.
+{{ ::studiesperteffect.png?nolink |}}
-===== OUTPUT =====
+===== Perturbation effect report =====
 The results page of the Perturbation effect tool is an ** interactive working environment **. You can **simulate knock outs or over-expressions of one or several genes ** or the ** effect of a drug** in the activity of signaling pathways.
@@ Line 105: / Line 126: @@
 Last update gene list
+==== Worked example and Interpretation of the results ====
+You can find an example of the use of this tool and the interpretation of the results at [[worked_example_perturbation_effect|Worked example: Perturbation effect]].