Software

Access the tool Here Access Github code Here

AFCMEasy Model was a tool developed as a part of Team AFCM-Egypt 2017 IGEM project. It is an interactive web tool that embeds R Codes used for modeling ceRNA networks to solve ODEs easily, specify parameters, rates and reaction species. The tool aimed to help other teams model their projects in an easy interactive way without facing technical issues.

And for this year, we decided to construct an efficient tool through improving and developing our previous made tool. It’s done via modification of the tool source code provided in Github to include the equations and parameters simulating replicon amplification which is the core. Thereby being beneficial to us and other teams who will depend on replicon in their projects to consume the time needed for the calculations and the simulation as well. In addition to consuming less time , You may

also save your plot as an image and modify the parameter values within a defined range to be suitable for each project.

The tool depends on a set of differential equations inspired by previous literature and further developed by our team.

Equation (1)

Plus-strand RNA, RPC, interacts with host cell ribosomes, (Ribo=10), to form a translation complex at an effective rate k1. RPC, by forming polysomes, disappears at rate k1 and reappears at rate k2 when translation is complete. Nucleases at the rate of MPC can be degraded by free plus-strand RNAs in the cytoplasm, lost from the cytoplasm by transport into VMS at the rate of kPin, and acquired by transport out of VMS at the rate of kPout.

Equation (2)

TC, which degrades at rate MT and Ribo represents a complex of 10 ribosomes to initiate translation concomitantly with RPC.

Equation (3)

Free viral polyprotein molecules, P, are produced by translation into separate viral proteins, including the enzymes responsible for viral RNA synthesis, at a rate of k2 per translation complex within the cytoplasm.

Equation (4)

Enzymes responsible for viral RNA synthesis, Ecyt, e.g., NS5B, at rate kc. Degraded before reaching the VMS at rate MEC, or transported into VMS at rate k8.

Equation (5-9)

In VMS, de novo development of RIPand RID complexes occurs with the rate constants k3 and k5, respectively, and degrades with the MP2 and MD2 rate constants. The nascent plus- and minus-strand RNAs are synthesised with rate constants of k4p and k4m , respectively. In VMS (RP and Rds), free plus-strand RNA and dsRNA degrade with MP and MD2 rate constants, respectively. Furthermore, the polymerase complex degrades or loses activity within VMS with a constant ME rate, which is probably lower than the MEC cytoplasmic degradation rate.

To make the simulations representative of the conditions that we wanted to test, we modified the parameters based on literature experimental values and fitting. The process of manual manipulation of parameter values is not flexible enough and also challenging in terms of time and computational power. That’s why we wanted to create a tool that allows us to manipulate the values easily to test different conditions in less time.