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what_can_do_hipathia_for_you [2020/01/31 13:28] – krianwhat_can_do_hipathia_for_you [2021/01/05 15:48] – [Hipathia mechanism] krian
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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). 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).
 {{ ::circuit.png?nolink |}} {{ ::circuit.png?nolink |}}
 +Once an "effector circuit" topology is known, Hipathia uses gene expression values as proxies of protein presence values, and consequently of potential protein activation values. Two types of nodes can be found: plain nodes and complex nodes. The first ones, are nodes which function (passing the signal form the previous node to the next one) is carried out by only one protein. However the functions of these nodes may be accomplished by more than one protein. In such case the node value is summarized as the percentile 90 of the values of the proteins contained in it. On the complex nodes, it is necessary the presence of more than one protein to pass the signal through. The minimum value of the proteins contained (the limiting component of the complex), is taken as the node activity value.
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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 "effector circuit".
 + {{ ::path_mechanism.png?nolink |}}
 +Finally, Hipathia also calculates the activation state of some molecular functions by looking at the functions annotated for the effector proteins in which the "effector circuit" finishes. With Hipathia's method it is possible to obtain an individual activation value of the different functions for each. Therefore it's also possible to infer which functions have different activation levels in the groups that are being compared. This feature is implemented for the annotations of the Uniprot database and Gene Ontology. 
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 +This video present a simple simulation of how Hipathia model calculates the propagated signal throw a signaling circuit:
 +{{ ::demoalgo.gif?nolink |}}
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 +===== HiPathia modules =====
  
 The HiPathia web server integrates four different pathway analysis modules: The HiPathia web server integrates four different pathway analysis modules:
what_can_do_hipathia_for_you.txt · Last modified: 2021/01/05 15:49 by krian