what_can_do_hipathia_for_you
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what_can_do_hipathia_for_you [2020/01/27 20:17] – krian | what_can_do_hipathia_for_you [2020/02/06 15:56] – [Hipathia mechanism] krian | ||
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Mechanistic models offer a realistic framework to understand how signal transduction depends on changes in the expression of genes involved in signaling pathway circuits (see [[http:// | Mechanistic models offer a realistic framework to understand how signal transduction depends on changes in the expression of genes involved in signaling pathway circuits (see [[http:// | ||
- | | + | ===== Hipathia mechanism ===== |
+ | HiPathia retrieves pathway information from [[https:// | ||
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+ | The purpose of a signalling pathway is to activate a cellular function carried out by an effector protein. This activation is given as a result of a cascade of protein interactions triggered by a stimulus captured by a receptor protein. | ||
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+ | In Hipathia, the activation values for the different effector circuit within a signalling pathway are calculated separately. One example might be the red-highlighted circuit on the figure below. These method was chosen because of the fact that many pathways are multifunctional and often trigger opposite functions (e.g. depending the receptor and the effector proteins involved in the transduction of the signal, the apoptosis pathway may trigger survival or cell death). | ||
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+ | Once an " | ||
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+ | In order to calculate the circuit signal, once the node activity values have been estimated, we assume an incoming signal value of 1 in the input nodes (stimuli-receptor proteins) of any circuit. Then, the signal is propagated to the following nodes as shown in the image above until it reaches its effector node. This is going to be the values that will be taken as the activation value for each " | ||
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+ | Finally, Hipathia also calculates the activation state of some molecular functions by looking at the functions annotated for the effector proteins in which the " | ||
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+ | This video present a simple simulation of how Hipathia model calculate the propagated signal throw a signaling circuit: | ||
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The HiPathia web server integrates four different pathway analysis modules: | The HiPathia web server integrates four different pathway analysis modules: | ||
* **Differential signaling** | * **Differential signaling** | ||
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The tool predicts the possible effect that gene disruptions produced by LoF (Loss of Function) variants can have over signaling circuits as well as the cellular functions triggered by them. | The tool predicts the possible effect that gene disruptions produced by LoF (Loss of Function) variants can have over signaling circuits as well as the cellular functions triggered by them. | ||
This module of HiPathia mechanistic model would be a specific case of the **perturbation effect** analysis, allowing the possibility of visualizing the effects of such perturbation for several tissues separately. also in this tool, the estimation can be done for more than one sample. | This module of HiPathia mechanistic model would be a specific case of the **perturbation effect** analysis, allowing the possibility of visualizing the effects of such perturbation for several tissues separately. also in this tool, the estimation can be done for more than one sample. | ||
- | A knock-down simulation is carried out on genes harboring LoF variants in a condition that represent a normal tissue. Then a **perturbation effect** analysis is carried out by comparing the condition with the simulated KOs with the normal condition. Normal conditions are taken from the repository of gene expression profiles of normal tissues available in the [[https:// | + | A knock-down simulation is carried out on genes harboring LoF variants in a condition that represent a normal tissue. Then a **differential signaling** analysis is carried out by comparing the condition with the simulated KOs with the normal condition. Normal conditions are taken from the repository of gene expression profiles of normal tissues available in the [[https:// |
Then, the signaling circuits potentially deregulated by the disruption of the gene/s provided by the user are detected and visualized. | Then, the signaling circuits potentially deregulated by the disruption of the gene/s provided by the user are detected and visualized. | ||
what_can_do_hipathia_for_you.txt · Last modified: 2021/01/05 15:49 by krian