fluxViz_RL

Hi Ritisha,

This is your page.  Please paste your google project description here and edit as you see fit throughout the project.  We can also use this page for communication, e.g. important decisions or noteworthy questions from our email or skype conversations could be listed here.

When you are ready, we will promote the relevant material to the main fluxViz page which is visible to the public.

mTOR (mechanistic Target Of Rapamycin) 

mTOR = Representative cell signaling network for fluxViz development

Big picture (what does mTOR do?):

• In the presence of growth factors, the mTOR kinase enzyme is active and cells grow/proliferate. 

• Cytoscape could represent growth factors (and other environmental inputs) as an explicit nodes that connect as input signals to other nodes in the system.  

• It would be nice if a disconnected node could have some global effect on all nodes in the system as well– can cytoscape do this?

GSoC 2013 goals for Ritisha: 

In order to focus on a deliverable tool by the end of the summer. 

• Version 1 of the project will:

  • only use binary on/off states for the nodes.

  • additional tables should be added to this page to explicitly define the attributes and data types, such as:

    • Node table: State (boolean, for v1.0)*

      • Start_Value (float, provided if known)

      • Flux_Value (float, calculated)

      • Threshold_to_Signal (float)

      • Input_Processing (logical or function?)

      • Signal_Value (float)

      • Signal_Delay (float)

    • * Other table: to handle meta data on states or …?

  • This sort of table can then be assessed in terms of what input data we are likely to be working with and what kind of output (i.e., numbers or visualizations) can we generate. 

  • The goal should be the simplest table model to support the most basic, useful functionality.

fluxVIZ features:

phosphorylated at the same time (not necessarily active, but receiving a signal):

• AKT

• S6K

• Sg

• 4EBP1

phosphorylated in rapa inhibited state:

• AKT is more phosphorylated

• 4EBP1

mTOR sketches:

Overview:

http://www.grahamj.com/PollardCellBiology/1eCD/data/animations/Flash2901.html

http://www.grahamj.com/PollardCellBiology/1eCD/data/animations/Flash2903.html

Future Development that should be planned for:

Oncogenes

• There are Oncogenes that work through this pathway to increase growth and proliferation

• An oncogene is a gene that has the potential to cause cancer

• In the mTOR fluxViz network, some nodes could be related to oncogenes either:

  • explicitly– via an edge connection to an oncogene node

    • The output of the oncogene node could modify the behavior of the connected protein in the mTOR pathway

  • implicitly– via a threshold counter in the node set to trigger a switch. In the future via a probabalistic modification of an attribute(s) in the node where a threshold still has a random component.

    • probabilisitc modification of an attribute of the node could have the possibility for change at every frame (e.g. if rand()>0.992: behaviorState+=1)

    • e.g. a mutatable attribute could be a probabilisitc modification in behavior of the node (based on the behaviorState value)

    • e.g. overexpression attribute could similarly increase some or all outputs of the node (based on the behaviorState value)

Structural biology aspect for future extension of fluxVIZ:

• Growth factors signal through two arms

  • the mTOR arm

  • the PI3K and Akt arm

• These can be independently inhibited, and while only inhibiting mTOR decreases growth, mTOR inhibition is not sufficient to completely turn off proliferation.